Efficacy of adjunctive photodynamic therapy to conventional mechanical debridement for peri-implant mucositis.

OBJECTIVE: This meta-analysis was conducted to assess the effectiveness of photodynamic therapy (PDT) as an adjunct to conventional mechanical debridement (CMD) for the management of peri-implant mucositis (p-iM). METHODS: We systematically searched four databases (PubMed, Embase, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) investigating PDT + CMD for p-iM from their inception to March 13, 2023. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Seven RCTs met the inclusion criteria. The meta-analysis revealed that PDT + CMD treatment was more effective than CMD alone in reducing probing depth (PD) (Mean Difference [MD]: -1.09, 95% Confidence Interval [CI]: -1.99 to -0.2, P = 0.02) and plaque index (PI) (MD: -2.06, 95% CI: -2.81 to -1.31, P < 0.00001). However, there was no statistically significant difference in the improvement of bleeding on probing (BOP) between the PDT + CMD groups and CMD groups (MD: -0.97, 95% CI: -2.81 to 0.88, P = 0.31). CONCLUSIONS: Based on the current available evidence, this meta-analysis indicates that the addition of PDT to CMD significantly improves PD and PI compared to CMD alone in the treatment of p-iM. However, there is no significant difference in improving BOP.

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Local Oxygen-Based Therapy (blue®m) for Treatment of Peri-Implant Disease: Clinical Case Presentation and Review of Literature about Conventional Local Adjunct Therapies.

Peri-implant diseases including peri-implant mucositis and peri-implantitis are among the major causes of failure of implant-supported dental restorations. They are characterized by progressive inflammation of the peri-implant mucosa, extending to the surrounding connective tissues and leading to bone loss and implant failure. Although strict oral hygiene practices help in preventing peri-implant diseases, plaque buildup around the implant restoration leads to chronic inflammation, due to the adherent bacterial biofilm. While mechanical debridement and non-surgical therapy to remove inflamed connective tissue (ICT) form the mainstay of treatment, additional local adjunctive therapies enhance clinical outcomes. Topical oxygen therapy is known to reduce inflammation, increase vascularity, and act as a bacteriostatic measure. The use of oxygen-based therapy (blue®m) products as a local adjunctive therapy for peri-implant mucositis and peri-implantitis can result in clinical outcomes similar to that of conventional local adjuncts such as chlorhexidine, antibiotics, and antibacterial agents. This report aims to present the clinical findings of patients with peri-implant mucositis and peri-implantitis, who were managed using local oxygen-based therapy as an adjunct to non-surgical therapy. In addition, a review of the literature about commonly used local adjuncts for peri-implant diseases has been included in the report to provide a means of comparison between conventional local adjunct therapy and topical oxygen-based therapy. Based on the reported findings and reviewed literature, local oxygen-based adjunct therapy was equally effective as conventionally used local adjuncts such as antibiotics, antibacterials, and probiotics, in treating patients with peri-implant diseases.

Short-term chemotherapy-related complications and undernutrition in children diagnosed with cancer at Korle Bu Teaching Hospital, Accra, Ghana: A prospective cohort study.

Undernutrition in children with cancer is associated with complications during cancer therapy. The study objective was to determine the association between specific anthropometric parameters and short-term chemotherapy-related complications and mortality. This was a hospital-based, prospective cohort study of children, age ≤12 years, with a new cancer diagnosis at the Paediatric Oncology Unit, Korle Bu Teaching Hospital, Ghana. Socio-demographic information, cancer characteristics and anthropometric measurements were obtained at enrolment. Participants were followed up for twelve weeks from commencement of chemotherapy and selected treatment-related complications such as anaemia and thrombocytopenia requiring transfusions, prolonged neutropenia resulting in treatment delays, febrile neutropenia, mucositis and death were recorded. A total of 133 participants were recruited with a median age of 4.5 years. Eighty-one (60.9%) were diagnosed with solid tumours, 31 (23.3%) had leukaemias and 21 (15.8%) had lymphomas. Of the anthropometric parameters assessed, only arm anthropometry using upper arm muscle area (UAMA) and mid-upper arm circumference (MUAC) were associated with complications. Participants with wasting were more likely to develop anaemia and mucositis. However, the incidence of prolonged neutropenia was significantly higher among participants with average UAMA (p = 0.043) and low average UAMA (p = 0.049) compared to those with low UAMA. Risk of neutropenia was also significantly less among those with wasting by MUAC compared to those well-nourished (p = 0.045). Twenty-three participants (17.3%) died with a greater proportion (11/44; 25%) occurring in those who were wasted using MUAC. These findings underscore the need for nutritional surveillance at diagnosis and during chemotherapy, particularly where co-morbid disease is prevalent.

Comparative Assessment of Catalase Levels in Peri-Implant Health and Disease.

Peri-implant disease pathogenesis is similar to periodontal disease pathogenesis resulting in production of pro-inflammatory mediators. These mediators alter the redox balance leading to decrease in antioxidants, among which catalase is one of the enzymatic antioxidants. The aim of the study was to compare the levels of catalase in peri-implant health and disease. The present observational study was carried out from June 2022 to December 2022 in the Department of Implantology, Saveetha Dental College and Hospitals, Chennai, India. A total of 60 patients with peri-implant health (Group 1; n = 20), peri-implant mucositis (Group 2; n = 20) and peri-implantitis (Group 3; n = 20) were enrolled. Unstimulated salivary samples were collected and subjected to ELISA for catalase analysis. Catalase levels were then compared between the groups using ANOVA. The mean catalase level in peri-implant health, peri-implant mucositis, peri-implanti-tis were 25.07 ± 0.44 U/mL, 18.5 6 ± 0.65 U/mL, and 11.25 ± 0.76 U/mL respectively. The difference between the three groups were statistically significant (P < 0.05). Catalase level decreases with severity of peri-implant diseases. Therefore, catalase can be used as a diagnostic marker for peri-implant diseases.

Comparative Evaluation of C-Reactive Protein Levels among Peri-Implant Health and Disease Conditions.

Peri-implant disease pathogenesis results in production of pro-inflammatory mediators, among which C-reactive protein (CRP) is one of the acute phase reactants. The aim of the study was to comparative CRP levels among peri-implant health and disease conditions. The present study was carried out in the Department of Implantology, Saveetha Dental College and Hospitals, Chennai, India. A total of 40 patients with peri-implant health (n = 10), peri-mucositis (n = 10), early peri-implantitis (n = 10) and advanced peri-implantitis (n = 10) were enrolled. Unstimulated salivary samples were collected and subjected to latex agglutination assay for CRP analysis. CRP levels were then correlated with peri-implant health and diseases. CRP level in peri-implant health, peri-implant mucositis, early peri-implantitis and advanced peri-implantitis were 0.18 ± 0.04 mg/dL, 2.05 ± 0.61 mg/dL, 4.14 ± 1.82 mg/dL and 6.21 ± 1.35 mg/dL respectively. There was a statistically significant difference in CRP levels between all the tested groups (ANOVA, P = 0.03). Pearson correlation coefficient analysis revealed a strong positive correlation between CRP and peri-implant health status. CRP level was high among patients with peri-implantitis followed by peri-implant mucositis and peri-implant health. Also, CRP level increases with severity of peri-implant diseases and there exists a positive correlation between CRP level and peri-implant health status.

Association between oral and fecal microbiome dysbiosis and treatment complications in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.

CEMENTED AND SCREW-RETAINED IMPLANT-SUPPORTED RESTORATIONS MAY HAVE A COMPARABLE RISK FOR PERI-IMPLANT MUCOSITIS AND PERI-IMPLANTITIS.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Reis INRD, Fukuoka GL, Nagay BE, Pannuti CM, Spin-Neto R, Silva EVFD. Incidence of peri-implant disease associated with cement- and screw-retained implant-supported prostheses: A systematic review and meta-analysis. J Prosthet Dent. 2023 Oct 2:S0022-3913(23)00563-2. doi:10.1016/j.prosdent.2023.08.030. Epub ahead of print. PMID: 37793953. SOURCE OF FUNDING: None declared. TYPE OF STUDY/DESIGN: Systematic review and meta-analysis.

Utilization of Photobiomodulation for the Prevention and Treatment of Oral Mucositis.

Background: Oral mucositis is a significant and common toxicity experienced by patients who receive high-dose chemotherapy as a preparatory regimen for a hematopoietic cell transplant (HCT). Photobiomodulation (PBM) has been found to be feasible with significant efficacy in preventing the progression of oral mucositis in adult patients undergoing HCT. The purpose of this study was to determine the feasibility and efficacy of PBM in pediatric oncology patients undergoing HCT. Method: Forty children and adolescents admitted to the transplant unit for an allogeneic HCT for acute lymphoblastic leukemia or acute myeloid leukemia were treated daily at six sites until day + 20 or engraftment. Results: There were 1,035 patient encounters, with successful treatment of four or more sites during 979 patient encounters for a feasibility 93.3% CI [0.926, 0.039]. We had estimated a meaningful effect size of 20% for PBM and estimated 51% of patients treated with PBM would have at least one day or more of Grade 3 mucositis. The rate of patients who received PBM and developed Grade 3 mucositis was 20% CI [0.091, 0.356]. Patients treated with PBM had fewer days of hospitalization (p = .009) and less severe mucositis in comparison to the matched control group (p = .03). Conclusion: PBM is feasible and effective in preventing and treating oral mucositis and is now supported by the Children's Oncology Group for prevention and treatment of oral mucositis in patients undergoing an allogeneic HCT or receiving head/neck radiation.

Increased frequency of oral plasma cell mucositis/plasma cell gingivitis after the COVID-19 pandemic: a 23-year retrospective analysis and review of diagnostic challenges relating to this condition.

OBJECTIVE: Oral plasma cell mucositis (PCM) or localized plasma cell gingivitis (PCG) is an idiopathic inflammatory condition often associated with hypersensitivity reactions. This study aimed to evaluate the frequency and features of PCM/PCG in a large biopsy service over a time period of more than 20 years. STUDY DESIGN: The biopsy archives at University of Florida College of Dentistry were searched from 2000 through the first quarter of 2023 for cases of oral PCM or PCG. Case data were aggregated and analyzed. RESULTS: A total of 107 cases were included. Between 2000 and 2019, PCM/PCG was diagnosed in 0.03% of all biopsy cases. Starting in 2020 through 2023, the percentage of biopsies diagnosed as PCM/PCG increased threefold to 0.10% of all biopsy cases, and the mean patient age increased by 3 years. There were no statistically significant differences between cases diagnosed from 2000 to 2019 and those from 2020 to 2023 regarding age, sex, location, or histology. CONCLUSIONS: A significant increase in PCM/PCG was identified in this study at one institution coinciding with the start of the COVID-19 pandemic. Further investigation is recommended to determine if this is a widespread phenomenon and identify possible etiologic mechanisms.

Clinical Efficacy of Different Concentrations of Povidone Iodine in the Management of Peri-Implant Mucositis.

Mechanical plaque control is the first line of management of peri-implant diseases. Povidone iodine is one of the broad spectrum and potent antiseptics available at various concentrations. The aim of the study was to assess and compare the efficacy of various concentrations of povidone iodine in the management of peri-implant mucositis. In the present double blinded, parallel designed, randomized clinical trial, a total of 60 patients with peri-implant mucositis (20 participants in each group [Group 1 (povidone iodine 0.1%), Group 2 (povidone iodine 2%) and Group 3 (povidone iodine 010%)] were enrolled. Scaling and root planing was done and then the peri-implant sulcus was irrigated with respective irrigant and repeated once in a week for 4 weeks. Loe and Silness Gingival Index (GI) and Mombelli Modified sulcular bleeding index (BI) were recorded at baseline and after a month and compared. Statistical analysis was done using One-way ANOVA and Tukey's HSD post hoc test. A statistically significant difference (P = 0.000) observed between the three concentrations when compared after 1 month. Also, a statistically significant difference between Group 1 and Group 3 and Group 2 and Group 3 was observed in terms of post GI (P = 0.000) and post BI (P = 0.000) but statistically no significant difference was observed between Group 1 and Group 2 in terms of post GI (P = 0.171) and post BI (P = 0.338). The 2% and 10% povidone iodine showed significant improvement in gingival index and bleeding index and hence it could be an effective adjunct to scaling and root planing in the management of peri-implant mucositis.

Correlation of C-Reactive Protein and Severity of Peri-Implant Diseases.

Peri-implant disease pathogenesis is similar to periodontal disease pathogenesis resulting in production of pro-inflammatory mediators. These mediators are released during the inflammation phase, among which C-reactive protein (CRP) is one of the acute phase reactants. The aim of the study was to correlate the levels of CRP with the severity of peri-implant diseases. The present observational study was carried out from June 2022 to December 2022 in the Department of Implantology, Saveetha Dental College and Hospitals, Chennai, India. A total of 60 patients with peri-implant health (n = 20), peri-mucositis (n = 20) and peri-implantitis (n = 20) were enrolled. Unstimulated salivary samples were collected and subjected to latex agglutination assay for CRP analysis. CRP levels were then correlated with severity of peri-implant diseases. The mean CRP level in peri-implant health, peri-implant mucositis, peri-implantitis were 0.25 ± 0.36 mg/dl, 3.56 ± 0.85 mg/dl and 5.07 ± 0.74 mg/dl, respectively. Pearson correlation coefficient analysis revealed a strong positive correlation between CRP and peri-implant parameters suggesting that the CRP level increased as the severity of peri-implant disease increased. CRP level increases with severity of peri-implant diseases and there exists a positive correlation between CRP level and peri-implant parameters. Therefore, CRP can be used as a diagnostic marker for peri-implant diseases.

Efficacy of Ozonated Olive Oil Gel in the Management of Peri-Implant Mucositis.

Peri-implant mucosistis is similar to gingivitis, the former affects the mucosa around implants without bone loss. The aim of this study was to determine the effectiveness of ozonated olive oil gel in the management of peri-implant mucositis. A randomized controlled clinical trial was conducted among 50 patients with peri-implant mucositis within the age group of 25-50 years. They were randomly divided into two groups with 25 participants in each group based on the intervention [Group A (Ozonated olive oil gel), Group B (Chlorhexidine gel)]. Silness and Loe plaque index (PI) and Loe and Silness gingival index (GI) were recorded at baseline and after 4 weeks. Paired t-test and independent t-test was used to test the significance. Within the groups, there was a statistically significant reduction in PI and GI from baseline (P < 0.05). However, the difference in PI and GI between both the groups was statistically insignificant (P > 0.05). Ozonated olive oil gel was equally effective to chlorhexidine gel in the management of peri-implant mucositis.

Orally Administrated Glutamate Restored EAAT1 and 3 Expression Levels Suppressed in 5-Fluorouracil-damaged Intestinal Epithelial Cells.

BACKGROUND/AIM: 5-Fluorouracil (5-FU) treatment induces intestinal mucositis, with diarrhea as the primary symptom. Mucositis significantly reduces patients' quality of life (QOL). Amino acids such as glutamate are beneficial for treating gastrointestinal disorders; however, the underlying mechanism remains unclear. Therefore, this study aimed to clarify the role of excitatory amino acid transporters (EAATs) in 5-FU-induced intestinal injury. MATERIALS AND METHODS: The rat intestinal epithelial cell line (IEC-6) was used to evaluate whether the EAAT inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) affects 5-FU-induced cytotoxicity. Mice with 5-FU-induced mucositis were used to determine the effects of glutamate on EAATs expression levels. RESULTS: Treatment with L-trans-PDC suppressed IEC-6 cell growth. It also exacerbated the 5-FU-induced cell growth suppression and increased inflammatory cytokine expression. In addition, mice treated with 5-FU+Glutamate showed higher EAAT1,3 expression than 5-FU only-treated mice. CONCLUSION: Decreased EAAT levels worsen intestinal cell damage caused by 5-FU, suppress cell growth, and induce inflammation. This study contributes to the understanding EAAT and its relationship with intestinal mucositis, which can aid in the development of novel preventive strategies for cancer chemotherapy.

The Potential Role of Probiotics, Especially Butyrate Producers, in the Management of Gastrointestinal Mucositis Induced by Oncologic Chemo-Radiotherapy.

Many clinical studies have now highlighted how the composition of the intestinal microbiota can regulate the effects of many oncological therapies. In particular, the modulation of microbial composition has been shown to enhance their efficacy and reduce potential side effects. Numerous adverse events induced by chemotherapy and radiotherapy appear to be strongly associated with an alteration in the intestinal microbiota caused by these treatments. This supports the hypothesis that the modulation or correction of the microbiota may decrease the toxic impact of therapies, improving patient compliance and quality of life. Among the most debilitating disorders related to oncological treatments is certainly mucositis, and recent clinical data highlight how the deficiency of short-chain fatty acids, especially butyrate, and specifically the lack of certain bacterial groups responsible for its production (butyrate producers), is strongly associated with this disorder. It is hypothesized that restoring these elements may influence the onset and severity of adverse events. Therefore, the intake of probiotics, especially butyrate producers, and specifically Clostridium butyricum (CBM588), currently the only cultivable and usable strain with a history of data proving its safety, could be a valuable ally in oncological therapies, reducing the associated discomfort and improving compliance, efficacy, and quality of life for patients.

Effectiveness of Glutamine Oral Care in Reducing Oral Mucositis and Improving Oral Health After Neurosurgery: A Randomized Controlled Trial with Microbiome Analysis.

BACKGROUND Hospital-acquired infections negatively impact the health of inpatients and are highly costly to treat. Oral care reduces the microorganism number in the mouth and lungs and is essential in preventing postoperative oral inflammation, lung infection, and other complications. This study was designed to determine the effects of oral care with glutamine on oral health, oral flora, and incidence of pneumonia in patients after neurosurgery. MATERIAL AND METHODS This was a parallel, double-blind, randomized trial. Patients admitted to the Neurosurgery Department of the hospital from July to October 2021 were selected. Three hundred patients who met the inclusion criteria were randomized into 3 groups. The control group (n=100) received oral care with routine oral nursing methods with saline, whereas the experimental group (n=100) received oral care with 5% glutamine. A compound chlorhexidine group (n=100) was set as a positive control. All patients, care providers, and investigators were blinded to the group assignment. The incidence of local debris, oral mucositis, halitosis, dryness, oral mucositis disorders, and oral flora types were collected and analyzed in all groups. RESULTS The incidence of local debris, oral mucositis, halitosis, dryness, and other oral mucositis disorders in the glutamine oral care group was significantly decreased, compared with that of the control group. Oral flora types in the glutamine and chlorhexidine groups were significantly reduced. CONCLUSIONS Oral care with 5% glutamine after neurosurgery is associated with a lower incidence of oral disorders and pneumonia, and a significant reduction in oral flora.