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Aim: To evaluate the clinical outcome and the associated factors of a treatment protocol for peri-implant mucositis. Materials and Methods: Patients were evaluated 30 months after a treatment protocol including professional mechanical debridement and modification of the prosthesis contours to improve access for biofilm control. Clinical performance was assessed by means of probing with an electronic pressure-calibrated periodontal probe. The possible impact of implant- and patient-level factors on the changes in peri-implant mucosal inflammation measured with the modified bleeding index (mBI) was evaluated. Results: Twenty patients and 61 implants were included in the analysis. At the final visit, 50% of the patients presented bleeding on probing, with a mean mBI of 0.22 (SD 0.27). The adjusted linear regression model showed a significant association between patient's compliance with supportive care visits (p = .006) and mucosal inflammation. Similarly, at the implant level, modified plaque index (p

Radiation-induced oral mucositis is a common and dose-limiting complication of head and neck radiotherapy with no effective treatment. Previous studies revealed that sildenafil, a phosphodiesterase 5 inhibitor, has anti-inflammatory and anti-cancer effects. In this study, we investigated the effect of sildenafil on radiation-induced mucositis in rats. Two doses of radiation (8 and 26 Gy X-ray) were used to induce low-grade and high-grade oral mucositis, separately. A control group and three groups of sildenafil citrate-treated rats (5, 10, and 40 mg/kg/day) were used for each dose of radiation. Radiation increased MDA and activated NF-κB, ERK and JNK signalling pathways. Sildenafil significantly decreased MDA level, nitric oxide (NO) level, IL1β, IL6 and TNF-α. The most effective dose of sildenafil was 40 mg/kg/day in this study. Sildenafil also significantly inhibited NF-κB, ERK and JNK signalling pathways and increased bcl2/bax ratio. In addition, high-dose radiation severely destructed the mucosal layer in histopathology and led to mucosal cell apoptosis in the TUNEL assay. Sildenafil significantly improved mucosal structure and decreased inflammatory cell infiltration after exposure to high-dose radiation and reduced apoptosis in the TUNEL assay. These findings show that sildenafil can improve radiation-induced oral mucositis and decrease the apoptosis of mucosal cells via attenuation of inflammation and oxidative stress.

Toothpastes are one of the most common personal care products among people of all ages. The various toothpaste types and their complex ingredients could cause irritation or allergic reactions. Allergic contact stomatitis has been often seen in clinical practice; however, desensitizing toothpastes as a trigger are often unrecognized. Here, we report three cases of allergic contact stomatitis due to stannous chloride-containing desensitizing toothpastes. General dentists and other professionals should pay more attention to the safety and adverse effects of toothpastes.

Chronic ulcerative stomatitis (CUS) is a rare disease of the mucous membranes with characteristics similar to other autoimmune diseases. The aim of this study was to conduct a systematic review of the literature to recover all reported cases of CUS in order to summarize what are the clinical, demographic, microscopic, immunological features of CUS and its therapeutic response to different drugs. A systematic review of the literature was carried out following the statements of preferred reporting items for systematic reviews and meta-analyses (PRISMA). The searches were performed in the electronic databases PubMed, Scopus, EMBASE, LILACS, Opengrey, and Google scholar. Inclusion criteria were articles or abstracts reporting at least one case with a final diagnosis of CUS. A total of 696 records were identified through databases, and 25 studies were selected reporting 81 cases. CUS affects more females (92%), and a greater number of cases are reported in Caucasian patients (53%). The age of patients ranged from 20 to 86 years with a mean age of 60 years (±13.86), and 15% of cases reported concomitantly skin lesions. The clinical and histopathological characteristics of CUS are very similar to those of oral lichen planus. The direct immunofluorescence (DIF) remains the gold-standard diagnostic resource and was performed in 69 cases, revealing a dotted pattern of deposition of stratified epithelium-specific antibodies (SES-ANA). The serum of 38 patients was collected for the performance of the indirect immunofluorescence (IIF), and the use of epithelial substrates such as monkey and guinea pig esophagus often resulted in positive SES-ANA IgG. Most patients were treated with antimalarials, and the treatment of choice that proved to be effective is hydroxychloroquine (HCQ). This entity must be considered in the differential diagnosis of other autoimmune diseases, as it may be underreported.

Nivolumab, an antibody against anti-programmed death type 1, has been used for treatment of advanced non-small cell lung cancer with improvement of overall survival. Usually, diarrhea, cutaneous rash, and pruritus are reported as the most common immune-related adverse effects of nivolumab therapy. Oral lesions and secondary adrenal insufficiency sometimes occur but usually are rare events. We report a case of a patient treated with nivolumab who then showed persistent oral ulcerative and lichenoid lesions, which were refractory to topical corticosteroids. The oral lesions were concomitant to nivolumab-induced adrenal insufficiency. These adverse events led to nivolumab discontinuation, which favored oral lesion healing and adrenal insufficiency remission. Through a brief review of the literature concerning nivolumab toxicity in the oral cavity, we discuss the clinical aspect and management of these lesions.

Aim: This study aims to evaluate the utility of genetic testing of patients diagnosed with periodic fever syndromes and to assess the validity of existing scoring criteria. Methods: This study retrospectively reviewed the clinical history of patients diagnosed with periodic fever syndromes at Queensland Children's Hospital between November 2014 and June 2018. Results: Forty-three patients were diagnosed with periodic fever syndromes. Diagnoses in the cohort included periodic fever, adenitis, pharyngitis and aphthous stomatitis (10), tumour necrosis factor receptor-associated periodic syndrome (9), cryopyrin-associated periodic syndrome (6), mevalonate kinase deficiency (4) while 14 remained unspecified. No presenting symptoms were uniquely associated with any particular diagnosis. Genetic testing of between 1 and 26 genes was performed in 26 (60%) patients. Two (7.7%) patients had pathogenic variants identified. Variants of uncertain significance which were insufficient to confirm a monogenic disorder were identified in a further 7 (27%) patients. The Eurofever classification criteria correlated with clinical diagnosis for patients diagnosed with cryopyrin-associated periodic syndrome (P = 0.046) and tumour necrosis factor receptor-associated periodic syndrome (P = 0.025) but not for patients diagnosed with mevalonate kinase deficiency (P = 0.47); however, the Eurofever classification criteria were often positive for more than one diagnosis in these patients. Conclusion: The European classification criteria can form a potentially useful tool to guide diagnosis; however, clinical judgement remains essential, because the score is often positive for multiple diagnoses. The diagnostic yield of genetic testing in this cohort was low and genetic testing may be more useful to confirm a strong clinical suspicion than to clarify a diagnosis for patients with less clear symptoms.

BACKGROUND Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of this toxicity in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection. AIM To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment. DESIGN Medical data and OM presentation were retrieved retrospectively from all patients younger than 18 years who were submitted to allo-HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters. RESULTS Forty-nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates. CONCLUSIONS A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients.

Pyodermatitis-pyostomatitis vegetans (PD-PSV) is rarely reported in the pediatric population. Here, we provide a review of pediatric PD-PSV in the literature and report a case of widespread PD-PSV in a 15-year-old male without a previous history of inflammatory bowel disease or gastrointestinal symptoms. Clinical, histological, and immunopathological workup established PD-PSV and revealed subclinical Crohn's disease. Treatment with infliximab was effective in inducing rapid resolution of the lesions.

Objectives This systematic review evaluated the evidence for the effectiveness of Photodynamic therapy (PDT) in treating oral fungal infections, as an alternative to conventional antifungal medications. Methods Five randomized control trials (168 participants) comparing the treatment of oral fungal infections using met with our inclusion criteria. Clinical and microbiological improvement was assessed by random‐effects meta‐analysis. Methodological quality assessment and heterogeneity were performed using peer‐reviewed criteria. PROSPERO registration: CRD42017076. Results PDT showed statistically non‐significant increased clinical efficacy (risk ratio (RR) = 1.47 [95% confidence interval (CI), 0.68; 3.17]; three studies, n = 108 participants, I 2 = 50%) and mycological efficacy (mean difference (MD) = 0.54 [95%CI, −0.71; 1.79]; three studies, n = 100; I 2 = 39%) at 30 days, as compared with conventional antifungal therapy. Lack of standardization of treatment parameters and variability in the assessment of outcomes was observed across the studies. All included studies had a moderate to low risk of bias. Conclusions PDT showed comparable effectiveness at treating oral fungal infections, particularly denture stomatitis. The small number of studies in this review, small sample size and variability of methods and outcome measures across studies, highlight the need for more standardized studies with longer follow‐up periods to enable recommendation of PDT as an alternative to conventional antifungal therapy.

Medicinal plant extracts are commonly applied for infectious diseases and are perceived as alternatives to conventional antimicrobial agents. We aimed to confirm the efficacy of phytotherapy for denture stomatitis compared with conventional therapies and placebo. A comprehensive literature search was conducted in Pubmed, Embase, Cochrane Library (CENTRAL), Scopus, and Web of Science, in addition to manual searching. Randomized controlled trials (RCTs) published in English, and studying the treatment of denture stomatitis with herbal medicines, were included. The outcome measures included the relief of clinical signs, reduced Candida colony counts, adverse effects, and patient satisfaction. Nineteen RCTs were included for a systematic review based on selection criteria. Two of them were analyzed using a random-effects model. There was no difference in the relief of clinical signs (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.43-2.15) and microbiological improvement (OR = 1.74; 95% CI: 0.55-5.45) between propolis and miconazole. Most of the included studies showed that phytomedicines had fewer side effects and more patient satisfaction than antifungals or disinfectants. However, further RCTs with more standardly prepared herbal formulations are required to verify the clinical efficacy of phytotherapy as an alternative or adjunctive therapy for denture stomatitis.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are the standard treatment for patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. Uncommon mutations, excluding exon 19 deletions and exon 21 L858R, comprise 7%–23% of EGFR mutation‐positive NSCLC. The treatment of uncommon EGFR mutation‐positive NSCLCs is controversial. Here, we present the case of an 81‐year‐old man who was diagnosed with lung adenocarcinoma cStage IVA harboring the uncommon EGFR L861Q mutation. The patient received oral afatinib treatment (40 mg/day). One month after the initiation of afatinib treatment, Common Terminology Criteria for Adverse Events version 4.0 grade 2 stomatitis was observed. It improved upon afatinib withdrawal. After 10 days of withdrawal, afatinib treatment was resumed at a reduced dose of 20 mg/day. Subsequently, the patient continued treatment with afatinib. A partial response to afatinib treatment was maintained for 49 months until primary tumor regrowth. Afatinib treatment was continued after disease progression, but the patient died of bacterial pneumonia 59 months after initiation of afatinib treatment. Several studies have previously reported a large number of compound mutations with uncommon mutations, and that compound mutation‐induced cells are most susceptible to afatinib. This suggests the efficacy of afatinib in clinical practice and that afatinib may be safely administered to elderly patients with appropriate dose reductions., A large number of compound mutations have been observed in patients with uncommon EGFR mutation‐positive NSCLC. Compound mutation‐induced cells are most susceptible to afatinib, suggesting the efficacy of afatinib in clinical practice. Afatinib may be administered to elderly patients with appropriate dose adjustments

BACKGROUND A complete understanding of oral mucositis (OM) is crucial to develop appropriate interventions to aid in the successful overall health outcome of paediatric patients undergoing haematopoietic stem cell transplantation (HSCT). AIMS This study aimed at determining the prevalence and severity of OM and at identifying the predictive factors that might aggravate OM at one-week, two-week and three-week post-HSCT. METHODS This retrospective, hospital-based study reviewed the medical records of 170 paediatric patients, summarising the patients' characteristics using descriptive statistics. Binary logistic regression was used to identify factors associated with the development of OM. RESULTS At one-week post-HSCT, 41% of 140 patients (n = 49) had developed OM, this was reduced at two-week (n = 36, 33%) and three-week (n = 13, 19%) post-HSCT. Univariate logistic regression revealed that patients with cancer (OR = 0.16, 95% CI = 0.05-0.54; p-value = .003) had a significantly lower prevalence of OM. Younger patients with an average age of 7.9 years old (OR = 0.85, 95% CI = 0.75-0.97; p-value = 0.013) and the presence of GvHD (OR = 2.37, 95% CI = 1.03-5.45, p-value = 0.042) were significantly related to a higher prevalence of OM. Multivariable logistic regression confirmed that the risk of OM is lower in patients with cancer compared to those with immunodeficiency syndromes or hereditary blood diseases (OR = 0.18, 95% CI = 0.04-0.77; p-value = .021). CONCLUSIONS This study identified a significantly lower prevalence of OM in patients with cancer compared to other conditions and that young recipients and those who developed GvHD were more likely to have OM.

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro‐inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies..

OBJECTIVES To investigate whether serum amylase can predict the recovery of salivary volume and determine the correlation of the level of cytokines, including epidermal growth factor, hepatocyte growth factor and keratinocyte growth factor, with oral mucositis during chemoradiotherapy for oral cancer. SUBJECTS AND METHODS This study included 84 patients treated with preoperative chemoradiotherapy followed by curative surgery, following a phase II study protocol. We measured and analysed the correlation of the stimulated saliva volume, serum amylase and cytokines in resting saliva at baseline and 1 month after chemoradiotherapy with oral mucositis levels. RESULTS We observed a negative correlation between the serum amylase level at the beginning of chemoradiotherapy and the stimulated saliva volume at 1 month after chemoradiotherapy (p = .03). Epidermal growth factor in resting saliva was significantly reduced after chemoradiotherapy (p

Objectives To determine whether treatment with tacrolimus plus sirolimus (Tac/Sir) as a prophylaxis for graft‐versus‐host disease worsens severe oral mucositis and delays healing compared to cyclosporine plus methotrexate (CsA/Mtx) following haematopoietic stem cell transplantation. Subjects and Methods The study comprised 141 patients: 73 randomized to receive Tac/Sir and 68 to receive CsA/Mtx. The oral mucositis assessment scale and toxicity grading according to WHO were used to assess the severity, peak and duration of oral mucositis from the day −3 to day 24 post‐transplant. Results Eighty‐seven patients developed oral mucositis in the first 24 days post‐transplant. No significant difference in oral mucositis severity between the Tac/Sir and CsA/Mtx groups was observed. The peak oral mucositis score occurred on day 10 in both groups. Although oral mucositis scores had returned to baseline in the CsA/Mtx group on day 24 post‐transplant, no significant difference compared with the Tac/Sir group was found. Conclusions The introduction of tacrolimus/sirolimus as a graft‐versus‐host disease prophylaxis in haematopoietic stem cell transplantation increased neither the incidence nor severity of oral mucositis compared with cyclosporine/methotrexate. Furthermore, oral mucositis healing was not prolonged and followed the same time pattern as cyclosporine/methotrexate.

Paracoccidioidomycosis (PCM) is an infection caused by fungi of the genus Paracoccidioides and is marked by a strong predilection for men; nevertheless, some women have had developed PCM and have presented oral involvement by the disease. OBJECTIVES To review all published cases until August 2020 of oral PCM in women, with emphasis on the presence of systemic changes, deleterious habits (tobacco and alcohol) and oral manifestation features through a systematic review. METHODS Observational studies (both prospective and retrospective) and case reports indexed in the Embase, PubMed, Scopus, Web of Science and LIVIVO databases were selected by two reviewers in a two-phase process following the pre-established PICOS criteria. RESULTS Twenty-five studies met the eligibility criteria and were selected for qualitative synthesis, of which 72 participants were enrolled. Brazilian White women between 40 and 50 years were the most affected and social history revealed them to be housewives or rural workers. Fifteen women (33.3% of the informed cases) presented any systemic change at the time of PCM diagnosis, namely pregnancy, HIV infection and/or depression. Moriform stomatitis was predominant and affected preferentially the gingivae and alveolar processes in the form of a single painful lesion. Most patients were treated with sulfamethoxazole + trimethoprim or itraconazole. CONCLUSIONS Oral PCM in women is rare; some cases showed systemic changes at the time of PCM diagnosis, namely HIV infection, pregnancy and depression. New studies should be conducted to elucidate the influence of systemic alterations on the development of oral PCM in women.

Background Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX). Aim To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high-dose of methotrexate (HD-MTX). Design Seventy-seven childhood patients receiving HD-MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated. MTX serum level, hepatic and renal function parameters, and presence and intensity of OM were analysed. Results The patients were submitted to 255 cycles of chemotherapy. OM was diagnosed in 191 (74.9%) cycles. Of these, 119 (46.6%) presented ulcerative lesions. Lymphoma was associated with severe OM (P = .01). OM was associated with higher serum levels of aspartate aminotransferase (P = .006), alanine aminotransferase (P = .04) and creatinine (P = .008). Increase of one unit of total bilirubin and indirect bilirubin associated, respectively, with 11% and 39% higher prevalence of OM. For each increase of one unit of creatinine serum level, it was observed a 37% higher prevalence of OM in patients with lymphoma. No association was found between delayed excretion of MTX and OM development. Conclusions OM is a prevalent complication of childhood cancer patients receiving HD-MTX. Renal and hepatic toxicity could be considered risk factors for OM, especially in patients with lymphoma.

Background Childhood patients have high risks for developing debilitating somatic and mental health side‐effects as a consequence of the many different approaches employed in treating their cancer. Early recognition and close monitoring of clinical and psychological problems are essential in planning appropriate interventions and preventing further deterioration. Case ePROtect was established as an easy‐to‐use application for daily self‐reporting of symptoms during cancer therapy. ePROtect includes six to eight questions pertaining to seven common symptoms: appetite loss, fatigue, nausea, pain, physical functioning, cognitive impairments and sleep quality. The case of a child diagnosed with Burkitt leukemia developing chemotherapy‐induced oral mucositis in home care is presented to show the therapeutic impact of early symptom detection with a daily web‐based tool. Conclusion This case highlights how electronic patient‐reported outcome measures (PROM) can directly facilitate patient care in real time and might be incorporated in future clinical routine.

Aims This prospective interventional study aimed to assess the efficacy of supersaturated calcium phosphate rinse and the use of an extra‐soft toothbrush twice a day when added to the existing oral hygiene protocol regimen (0.12% chlorhexidine gluconate + 3% sodium bicarbonate + nystatin 5000 U/mL) in reducing the severity of oral mucositis among pediatric patients receiving chemotherapy for the hematopoietic stem cell transplant. Methods Forty‐five patients that received chemotherapy for the hematopoietic stem cell transplant were randomly allocated to three groups of 15 patients each. Group A was advised to follow the existing oral hygiene protocol regimen (Control), group B was advised to brush their teeth twice daily using an extra‐soft toothbrush and to follow the control regimen, and lastly group C was advised to use supersaturated calcium phosphate rinse and to follow the control regimen. Oral mucositis was recorded according to World Health Organization criteria from the day of admission (day 1) to the day of discharge (day 28). The incidence of oral mucositis between the three groups was compared using the Kruskall‐Wallis test while the severity of oral mucositis between the three groups was compared using a one‐way ANOVA test. Results The results of the study showed no significant difference in the incidence of oral mucositis between the three groups; however, there was a lower severity of oral mucositis in the supersaturated calcium phosphate rinse group when compared to the control group or the group who used an extra‐soft toothbrush with the control regimen. Conclusion Although marginally fewer cases and lower severity of oral mucositis was observed in the group using supersaturated calcium phosphate rinse, the lack of statistical significance suggests that the evidence for their use is not conclusive. The results of this study also showed that the introduction of an extra‐soft toothbrush into the oral hygiene regimen did not significantly reduce the incidence of oral mucositis and may actually be responsible for an increase in the severity of oral mucositis.

Aims The final diagnosis of oral mucosal ulcerations in solid organ transplant recipients represents a challenge. We describe a unique case of oral ulceration related to mycophenolate mofetil (MMF) toxicity, 11 years after kidney transplantation, whose dose reduction was sufficient to resolve it. Methods and results A 54-year-old female patient, who underwent kidney transplantation 11 years ago, presents multiple ulcers on the buccal mucosa bilaterally, soft palate and tongue dorsum, for 8 months, with moderate pain. The diagnosis of oral ulcerations associated with MMF therapy was assumed by excluding infection and malignancy diagnosis. After MMF dose reduction, the oral ulcers healed utterly. Conclusions MMF toxicity manifested as oral ulcers. Reduction or discontinuation of MMF therapy should be considered in a patient with refractory oral ulcers and a negative workup for other causes.

Background This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian®) plus cisplatin (SP regimen) and 5‐fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA‐NPC). Methods Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco‐regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. Results In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow‐up period, the estimated 3‐year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3‐year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3‐4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). Conclusions These data indicate that SP and FP therapies have similar efficacy in treating LA‐NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA‐NPC treatment., The incidence of other adverse effects seen in both groups was similar (P > .05).The efficacy of both regimens i.e. SP and FP are found similar. The SP regimen has tolerable safety profile, with a lower incidence of severe OM and consequently, an improved quality of life.

OBJECTIVE Methotrexate (MTX) increases the risk of alopecia and stomatitis, but the prevalence of these adverse events among rheumatic patients taking MTX is poorly defined. We conducted a systematic literature review and meta-analysis to estimate the prevalence of alopecia and stomatitis with MTX in rheumatic diseases. METHODS We searched PubMed, The Cochrane Library, and CINAHL databases for double-blind randomized controlled trials (RCTs) with an MTX monotherapy arm. Alopecia, stomatitis, and oral/mouth ulcers data were extracted. The quality of trials was assessed by 2 authors. We included trials published since 1990 that used at least 10 mg of MTX weekly, coadministered with folic or folinic acid. We estimated the prevalence using random-effects models because heterogeneity was anticipated. Two estimates of prevalence were included; the lower bound estimate included all trials (assuming no alopecia and stomatitis if not mentioned), and the upper bound estimate included only those that specifically described prevalence estimates of alopecia or stomatitis. RESULTS Of 3,954 studies identified, 20 RCTs were included, with a total of 24 MTX monotherapy arms, of which 10 reported the prevalence of alopecia (n = 1,113), and 21 reported stomatitis or mouth/oral ulcers (n = 2,056). The prevalence of alopecia was between 1.0% and 4.9%. The prevalence of stomatitis was between 5.7% and 8.0%. CONCLUSION This meta-analysis gives more precise estimates of mucocutaneous adverse events that occur in rheumatic disease patients taking MTX. These estimates will help inform patient decision-making regarding MTX.

Background The 2017 World Workshop classified peri-implant diseases into health, peri-implant mucositis, and peri-implantitis. The aim of this article is to build upon this recent classification and propose a framework for the diagnosis of peri-implant status after surgical treatment for peri-implantitis. Methods A literature review was conducted to discuss the relevant diagnostic, clinical, and radiographic parameters, including probing depth, bleeding on probing, visual inspection, and radiographic bone loss. Case definitions of possible treatment outcomes were discussed, and a flowchart was constructed to guide post-treatment diagnosis according to the possible clinical scenarios which can be encountered in daily practice. Results Three possible treatment outcomes were identified after resective treatment of peri-implantitis: 1) peri-implant health with a reduced support, 2) peri-implant mucositis with a reduced support, and 3) recurrent/refractory peri-implantitis. After regenerative treatment for peri-implantitis, the peri-implant condition was classified according to the same diagnoses with the addition of peri-implant health or peri-implant mucositis after complete regeneration for cases where complete regeneration was attained. Criteria for successful treatment of peri-implantitis were proposed. After resective therapy, a successful treatment outcome was defined as peri-implant health with a reduced support, whereas, after regenerative therapy, a successful outcome was described as either peri-implant health after complete regeneration or peri-implant health with a reduced support. Conclusions The proposed classification system of peri-implant status after surgical treatment for peri-implantitis provides a framework for diagnosing the various forms of peri-implant stability or disease to guide clinical decision-making post-treatment.

AIMS This study aimed to evaluate the effect of laser photobiomodulation in the prevention of oral mucositis (OM), salivary hypofunction and referred pain in patients with head and neck cancer. METHODS AND RESULTS This randomized clinical study divided patients into two groups: the laser group (LG, n = 30) and the control group (CG, n = 24). The LG (InGaAlP, 660 nm, 86.7 mW, 2 J/cm2 ) participated in the preventive protocol, while the CG underwent a simulated procedure without light emission. The degree of OM, salivary flow, and referred pain were evaluated at five different periods of radiotherapy. Both groups showed a significant increase in the degree of OM (P

Background In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behcet 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.

In a subgroup of Japanese patients in the ARCHER 1050 randomized phase 3 trial, we evaluated the efficacy and safety and determined the effects of dose modifications on adverse events (AE) and therapy management of first‐line oral dacomitinib 45 mg compared with oral gefitinib 250 mg, each once daily in 28‐d cycles, in patients with EGFR‐activating mutation–positive (EGFR‐positive; exon 19 deletion or exon 21 L858R substitution mutations) advanced non‐small cell lung cancer (NSCLC). The primary endpoint was progression‐free survival (PFS; RECIST, version 1.1, by blinded independent review). In 81 Japanese patients (40 dacomitinib, 41 gefitinib), PFS was longer with dacomitinib compared with gefitinib (hazard ratio [HR], 0.544 [95% confidence interval {CI}, 0.307‐0.961]; 2‐sided P = .0327; median 18.2 for dacomitinib [95% CI, 11.0‐31.3] mo, 9.3 [95% CI, 7.4‐14.7] mo for gefitinib). The most common Grade 3 AEs were dermatitis acneiform with dacomitinib (27.5%) and increased alanine aminotransferase with gefitinib (12.2%). A higher proportion of patients receiving dacomitinib (85.0%) compared with gefitinib (24.4%) had AEs leading to dose reduction. Incidence and severity of diarrhea, dermatitis acneiform, stomatitis and paronychia were generally reduced after dacomitinib dose reductions and dacomitinib treatment duration was generally longer in patients with a dose reduction in comparison with those without a dose reduction. Our results confirmed the efficacy and safety of first‐line dacomitinib in Japanese patients with EGFR‐positive advanced NSCLC., We evaluated the efficacy and safety of first‐line dacomitinib compared with gefitinib in a subgroup of Japanese patients with EGFR‐activating mutation–positive advanced non‐small cell lung cancer who were enrolled in the ARCHER 1050 randomized phase 3 trial. Results for the primary efficacy endpoint in the Japanese patients (n = 81) were consistent with the results in the overall ARCHER 1050 population; there was a clinically meaningful prolongation of median PFS by 8.9 mo favoring dacomitinib. The safety profile of dacomitinib was manageable by dose reduction or temporary dose interruption and no new safety signals were observed in the population of Japanese patients compared with the overall ARCHER 1050 study population.

Objective The aim of this study was to characterize clinical and histopathological features, and management outcomes of patients with oral immune-related adverse events (irAEs) secondary to programmed cell death-1 (PD-1) inhibitors. Methods This was a case series of cancer patients receiving PD-1 inhibitor therapy who were referred to oral medicine for the development of oral irAEs. Demographic, clinical, and histopathological data were collected from electronic medical records. Results There were 13 patients (7 males) with a median age of 68 years (range: 39-82) who were treated with nivolumab (n = 7) or pembrolizumab (n = 6). Oral irAEs included lichenoid lesions (n = 10), erythema multiforme (EM) (n = 2), and acute graft-versus-host disease reactivation (n = 1), with or without ulcerations (n = 8). Four patients (31%) presented with only oral irAEs. Oral biopsies showed lichenoid mucositis (n = 4). Management with topical and systemic steroids led to complete symptomatic response in most patients (n = 12). PD-1 inhibitor therapy was temporarily discontinued (n = 3) and discontinued indefinitely (n = 2) due to severe oral irAEs. Conclusion Patients receiving PD-1 inhibitors may develop oral irAEs characterized by lichenoid lesions, ulcers, or EM. Topical and systemic steroids appear to be effective in managing oral lesions although the severity of irAEs may necessitate PD-1 inhibitor therapy dose modification.

Objective The objective of this study was to prospectively evaluate the clinical features of chemotherapy‐induced oral mucositis (CIOM) in adult patients with acute leukemia and the aggravating factors for such symptoms. Subjects Thirty‐seven prospective patients aged ≥19 years with acute leukemia undergoing chemotherapy were enrolled. Oral and clinical investigations were performed at baseline and on Day 14 after starting chemotherapy. The presence and severity of cancer‐induced oral mucositis were demonstrated using the World Health Organization (WHO) scoring system. Results On Day 14, we found that oral mucositis had developed in eight patients (21.6%). Hematopoietic stem cell transplantation (HSCT) in patients was a predictor of increased WHO scores (β = 1.937, p < .001). Regarding oral sites, ventral tongue (β = 1.670), soft palate (β = 1.242), and buccal mucosa (β = 0.593) were predictors for increased scores. In addition, the increase in WHO scores was positively correlated with the number of oral lesions (r = .521), the difficulty in eating (r = .250), and the overall oral health (r = .534; all p < .05). Conclusion The main factors affecting the severity of CIOM symptoms were the treatment with HSCT and the location of oral lesions. The incidence of CIOM and WHO scores were not significantly different between the subgroups of disease. Our findings will help clinicians investigate the oral findings after chemotherapy in adult patients with acute leukemia.

Objective This study was designed to investigate whether necroptosis is involved in the pathogenesis of chemoradiation-induced oral mucositis in a murine model and whether 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) ameliorates this disorder. Materials and methods A chemoradiation-induced oral mucositis model was established by treating mice with concurrent 5-fluorouracil (100 mg/kg, i.p.) and head and neck X-irradiation (20 Gy). Phosphate-buffered saline or PLAG (100 mg/kg or 250 mg/kg, p.o.) was administered daily. Body weights were recorded daily, and mice were sacrificed on Day 9 for tongue tissue analysis. Results On Day 9, chemoradiotherapy-treated (ChemoRT) mice had tongue ulcerations and experienced significant weight loss (Day 0:26.18 ± 1.41 g; Day 9:19.44 ± 3.26 g). They also had elevated serum macrophage inhibitory protein 2 (MIP-2) (control: 5.57 ± 3.49 pg/ml; ChemoRT: 130.14 ± 114.54 pg/ml) and interleukin (IL)-6 (control: 198.25 ± 16.91 pg/ml; ChemoRT: 467.25 ± 108.12 pg/ml) levels. ChemoRT-treated mice who received PLAG exhibited no weight loss (Day 0:25.78 ± 1.04 g; Day 9:26.46 ± 1.68 g) and had lower serum MIP-2 (4.42 ± 4.04 pg/ml) and IL-6 (205.75 ± 30.41 pg/ml) levels than ChemoRT-treated mice who did not receive PLAG. Tongue tissues of mice who received PLAG also displayed lower phosphorylation levels of necroptotic signalling proteins. Conclusion 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol mitigated chemoradiation-induced oral mucositis by modulating necroptosis.

Aim Few data are available regarding the long-term impact of supportive implant therapy (SIT) on peri-implant diseases. We present long-term results on the possible effects of SIT on the peri-implant tissues. Material and methods In a private practice, 50 consecutive patients with 101 implants had attended an SIT programme for >6 years (SIT group). A second consecutive group comprised patients without SIT compliance (C group). We assessed pocket probing depth (PPD), bleeding on probing (BOP), bone loss (BL) and implant hygiene (QHI). Correlations between SIT compliance and the prevalence of peri-implant diseases were evaluated statistically. Results The inclusion criteria were met by 48 patients with 98 implants (SIT group) and 43 patients with 121 implants (C group). SIT group: Mucositis rate 30%; mean PPD 3.76 ± 0.86 mm; bone loss 1.02 ± 0.85 mm, peri-implantitis rate 4%. C group: Mucositis rate 68%; mean PPD 4.07 ± 1.18 mm; bone loss 1.53 ± 1.46 mm; and peri-implantitis rate 17%. Significant associations were found between SIT compliance and reduced peri-implant mucositis (p = .019), reduced highest PPD (p = .038) and peri-implantitis rates (p = .027). Conclusions Patients under SIT were associated with lower incidence of peri-implant diseases. Patients without regular maintenance might exhibit a 4.25-fold increased risk for peri-implantitis. Therefore, SIT programmes should be considered essential.

Purpose To evaluate the prevalence of peri-implantitis (PI) and peri-implant mucositis (PM) in a long-term follow-up with comparison among different PI and PM definitions, and to report on the incidence of PI. Materials and methods In a retrospective clinical study five different PI and PM definitions were applied onto a population with 274 implants 17 to 23 years postimplant placement. Recommendations by the Eighth European Workshop on Periodontology (EWOP) were used as base reference. Clinical and radiological measurements were considered. Risk factors were evaluated in a regression analysis. Results After an average observation period of 18.9 years, 40.1% of the implants were diagnosed with PM and 15.0% with PI (Eighth EWOP). PI incidence reached 7.9% on implant level and 13.2% on patient level. Implants diagnosed with PI and progressive bone loss displayed exceptionally vertical bone defect configuration (BDC). Diabetes mellitus, smoking, regular maintenance, or a former periodontal infection did not show significant influence on the prevalence of peri-implant diseases. Patients with bruxism displayed significantly less PM and PI. Conclusions Vertical BDC seems to correspond with active PI, wherefore we estimate such a defining factor of importance. Diagnosis of PM and evaluation of probing pocket depths might be only of descriptive interest as they could lead to false-positive results.

This report highlights azathioprine‐induced severe myelosuppression in the patient with NUDT15 minor variant. This case report is particularly instructive because several typical symptoms are the clues to this critical adverse drug reaction.

The use of dental implants is nowadays a well-accepted and highly predictable treatment modality for restoring the dentition and reestablishing the masticatory function of edentulous and partially edentulous patients. Despite the high predictability and excellent long-term survival rates reported for implant therapy, complications may still occur and can jeopardize both short- and long-term success. The present paper provides an overview on the most important aspects related to the etiology, prevention, and management of complications associated with implant therapy. Data from the literature indicate that a number of factors, such as surgical trauma, implant diameter, type of implant-abutment connection, abutment disconnection and reconnection, presence of microgap, and implant malpositioning, can substantially influence the biologic processes of bone remodeling and biofilm formation, thus increasing the rate of short- and long-term hard- and soft-tissue complications. Other factors, such as excess cement at cement-retained prosthetic restorations, abutment mobility, and infections (e.g. peri-implant mucositis and peri-implantitis) caused by bacterial biofilm, are further causes for complications and failures. More recent evidence also indicates that besides the need for sufficient bone volume surrounding the implant, the presence of an adequate width and thickness of attached mucosa may improve biofilm control and limit crestal bone resorption. Furthermore, emerging evidence points also to the pivotal role of human factors as one of the most important causes of complications in implant dentistry. It can be concluded that clinicians need to consider all biologic and biomechanical factors affecting implant placement and survival, as well as undergo adequate training to improve their surgical skills to control and prevent implant complications. Careful patient selection and control of environmental and systemic factors, such as smoking, diabetes etc., coupled with an accurate surgical and prosthetic planning, enable a better prevention and control of infections.

Background and objectives Mucositis is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), and is caused by a combination of conditioning-induced mucosal damage and severe neutropenia. The symptoms include oral and abdominal pain, inability to swallow food and fluids, and severe diarrhoea. Severe mucositis is associated with increased risk of Graft-versus-Host disease and infection. Granulocyte transfusions (GCX) could be a treatment option, and our objective was to study its feasibility and potential benefits. Material and methods This retrospective, single-centre study included 30 patients receiving GCX because of severe oral mucositis after HSCT during 2005-2017. Clinical outcome, response to GCX, change in opiate administration and adverse events were studied. Results Twenty-seven patients received GCX from donors pre-treated with steroids and G-CSF, and three from donors pre-treated with steroids only. Overall response was 83% (24/29 evaluable patients). Fifteen patients reached a complete response. In 14 of 24 responders, a reduction of the administration of opiate pain relief was seen. In eight patients this reduction was ≥50% of the dose. Adverse events (AEs) were reported in 14 cases, and were mild to moderate, and well manageable with symptomatic treatment. No life-threatening or fatal AEs were recorded. Conclusions These results indicate that GCX could be a safe and effective treatment for oral mucositis after HSCT with the potential to reduce the necessity of opiate analgesic treatment in this disorder. No severe AEs were seen in this study, but the risk for severe pulmonary AEs after GCX needs to be considered.

AIM To evaluate the adjunctive effect of modifying the implant-supported prosthesis to facilitate access to oral hygiene when treating peri-implant mucositis. MATERIAL AND METHODS A 6-month randomized clinical trial was designed. Patients with peri-implant mucositis were treated by implant surface debridement with plastic curettes and a plastic tipped ultrasonic device. Then, they were randomly assigned to either modifying their prosthesis to allow for better oral hygiene (test group) or not (control group). Subsequently in both groups, individualized oral hygiene instructions were provided. Clinical and radiographical outcomes were evaluated at baseline and 1, 3 and 6 months after treatment. RESULTS 48 patients were included, and 45 completed the clinical trial (24 test and 21 control patients). After 6 months, changes in the modified bleeding index between the control and test groups were 0.50 (standard deviation -SD = 0.70) and 1.14 (SD = 0.96), respectively (p = 0.01). The changes in implant probing pocket depth at 6 months were -0.02 (SD = 0.61) and 0.31 (SD = 1.20) mm, respectively (p = 0.04). CONCLUSIONS Modifying the contour of the prostheses to improve access for oral hygiene significantly improved the clinical outcomes after standard mechanical treatment of peri-implant mucositis.

OBJECTIVE To evaluate the influence of supportive treatment (SPT) during a maintenance period after implant placement on implant survival rate (SR) and incidence of peri-implant diseases. MATERIAL AND METHODS A systemic literature search for studies published up to June 2018 was conducted by two independent reviewers using Pubmed/MEDLINE, EMBASE, and Cochrane Central databases. Clinical controlled trials (CCT) involved in SPT protocol with more than 1-year follow-up were included. Quantitative meta-analyses were carried out to analyze the risk ratio (RR) of SR, the incidence of peri-implantitis, and peri-implant mucositis between SPT and non-SPT groups. Any potential confounding factors were investigated using meta-regression. RESULTS Nine CCTs fulfilled the criteria. To evaluate the influence of SPT on SR, peri-implantitis, and peri-implant mucositis, six of nine, three of nine, and three of nine articles were included in further meta-analysis, respectively. SPT group significantly showed higher SR (RR: 1.10; p

Purpose To evaluate the effects of oral supplementation on the management of oral mucositis in patients with cancer undergoing chemo and/or radiation therapy. Method This is a systematic review and meta-analysis. The search was performed at 6 databases, and in the gray literature. Methodology of included studies was evaluated by the Cochrane Collaboration Risk of Bias Tool, and evidence quality was assessed by GRADE instrument. Results Twelve randomized clinical trials were included in this review. The oral supplementation used was an oral elemental diet with amino acids and minerals (elental), glutamine, and zinc. The majority of the studies included in this review showed benefits in delaying the occurrence of OM by using glutamine and zinc, and in reducing the severity of OM with glutamine, zinc, and elental in patients receiving chemoradiotherapy. The meta-analysis showed that the risk of oral mucositis in the zinc group was slightly lower than in the control (RR: 0.71, 95% CI: 0.53-0.96, P = 0.02, n = 982) while the glutamine group presented the same risk as the control (RR: 0.91, 95% CI: 0.78-1.05, P = 0.19, n = 314). The evidence quality suggested low confidence for zinc and glutamine studies in the estimated effect from the outcomes assessed. Conclusions Zinc is a promising strategy in the management of oral mucositis since it delayed the occurrence and reduced its severity. Glutamine and Elental, on the other hand, had no strong evidence in the prevention and/or treatment of oral mucositis in patients with cancer.

Recurrent oral ulcerations are manifestations of a heterogeneous set of both general and more-or-less specific oral diseases due to numerous potential etiologies, including, but not limited to, infections, medications, autoimmune disease, and other systemic disease. This review discusses the pathogenesis, clinical presentation, diagnosis, and management of the common causes of recurrent oral ulceration. The following types/etiologies of recurrent oral ulceration are covered: traumatic ulceration, chemical ulceration, recurrent aphthous stomatitis, medication-related ulceration, infectious ulceration, mucocutaneous disease, and autoimmune/systemic disease. A diagnostic algorithm for recurrent oral ulceration is also presented.

BACKGROUND This study aimed to determine the effect of the consumption of a probiotic on the clinical characteristics of Candida-associated denture stomatitis (DS) and to determine the impact of a protocol of self-care measures in oral/prosthetic hygiene in institutionalized elders that wear removable prostheses (RP). The current treatment for DS is the systemic use of antifungals, as well as the replacement of these devices together with oral/prosthetic hygiene instructions. METHODS This study was a randomized, controlled and triple-blind trial. Thirty-six elders presenting DS of different severity and who carried RP consumed milk with/without the probiotic L. rhamnosus SP1. The prevalence and severity of DS and prevalence of Candida were determined and all participants/caregivers were trained in oral/prosthetic hygiene. RESULTS In both groups a decrease in the prevalence of DS was observed (P