This network meta-analysis aims to compare the clinical efficacy of seven non-surgical therapies for peri-implant disease, including laser treatment, photobiomodulation therapy (PBMT), photodynamic therapy (PDT), systemic antibiotics (SA), probiotics, local antimicrobials (LA), and air-powder polishing (APP) combined with mechanical debridement (MD). We conducted searches in four electronic databases, namely PubMed, Embase, Web of Science, and The Cochrane Library, to identify randomized controlled trials of non-surgical treatments combined with MD for individuals (aged at least 18 years) diagnosed with peri-implantitis or peri-implant mucositis with a minimum of 3 months follow-up. The outcomes of the study were the reduction in pocket probing depth (PPD) and bleeding on probing (BoP), plaque index (PLI), clinical attachment level (CAL), and marginal bone loss (MBL). We employed a frequency random effects network meta-analysis model to combine the effect sizes of the trials using standardized mean difference (SMD) and 95% confidence intervals (CIs). Network meta-analyses include network plots, paired comparison forest plots, league tables, funnel plots, surface under the cumulative ranking area (SUCRA) plots, and sensitivity analysis plots. The results showed that, for peri-implantitis, PBMT +MD demonstrated the highest effect in improving PPD (SUCRA = 75.3%), SA +MD showed the highest effect in improving CAL (SUCRA = 87.4%, SMD = 2.20, and 95% CI: 0.38 to 4.02) and MBL (SUCRA = 99.9%, SMD = 3.92, and 95% CI. 2.90 to 4.93), compared to MD alone. For peri-implant mucositis, probiotics +MD demonstrated the highest effect in improving PPD (SUCRA = 100%) and PLI (SUCRA = 83.2%), SA +MD showed the highest effect in improving BoP (SUCRA = 88.1%, SMD = 0.77, and 95% CI: 0.27 to 1.28), compared to MD alone. Despite the ranking established by our study in the treatment of peri-implant disease, decisions should still be made with reference to the latest treatment guidelines. There is still a need for more high-quality studies to provide conclusive evidence and especially a need for studies regarding direct comparisons between multiple treatment options.

OBJECTIVE: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever.
METHODS: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge.
RESULTS: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia.
CONCLUSIONS: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI.
BACKGROUND: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

This case study studies the adverse effects of methotrexate toxicity as well as the importance of early recognition of the symptoms and signs of methotrexate toxicity. This study involves a 54-year-old female who accidentally took methotrexate in high doses for a period of five consecutively days. The patient had been diagnosed with mixed connective tissue disease and was being treated with methotrexate once weekly. However, she took 7.5 mg (three tablets) three times a day for five days instead of 15 mg once weekly in two divided doses. The patient immediately went to the ER but was asymptomatic and discharged after a CBC showed values within the normal range. The patient was then seen by her primary care physician and advised to return to the ER. At this time, the patient had mucocutaneous lesions and was complaining of oral and throat pain, and a repeat CBC demonstrated pancytopenia. The patient was admitted to the hospital for further management and treatment of methotrexate toxicity.

Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota\'s contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.

BACKGROUND: Due to their modulatory effect on biofilm growth, bacterial gene expressions, and host-modulation effects, fermented foods and probiotic products could potentially have a protective role against peri-implant diseases. This cross-sectional study aimed to examine the association of consumption of fermented foods and products containing probiotics, with peri-implant health and diseases.
METHODS: A total of 126 implants were included. The peri-implant health status (peri-implantitis, peri-implant mucositis, and peri-implant health) was assessed through Chicago\'s Classification of periodontal and peri-implant Diseases and Conditions. A questionnaire was used to evaluate the consumption patterns of fermented and probiotic foods and product. One-way ANOVA was employed to compare the 3 peri-implant conditions categories in terms of fermented food and probiotic consumption.
RESULTS: There were significant differences in the daily and general consumption of yogurt, probiotic yogurt, kefir, ayran, vinegar, pomegranate syrup, whole meal bread, and homemade butter among peri-implantitis, peri-implant mucositis and peri-implant health (p < 0.05). The peri-implant health group consumed significantly more yogurt, kefir, ayran, vinegar, whole wheat bread, and homemade butter than peri-implant mucositis and peri-implantitis.
CONCLUSIONS: A higher consumption of fermented and probiotic foods may be associated with peri-implant health. Fermented and probiotic products may be useful for prevention of peri-implant diseases in patients with implants.

UNASSIGNED: Chemotherapy-induced mucositis is inflammation that develops in the oral mucosal due to anticancer treatment. Mucositis has negative consequences that may lead to distress in pediatric patients, resulting in escalated expenses, diminished quality of life, hindrance in cancer therapy, and decreased survival rates. However, despite the numerous methods, oral care protocols are suggested for implementation in the pediatric population despite a lack of high-level evidence studies, particularly regarding which appropriate oral care agents should be administered.
UNASSIGNED: This systematic review aimed to identify the effect of oral care intervention in mucositis management among pediatric cancer patients.
UNASSIGNED: Studies were published between 2014 and 2023 from five databases: PubMed, Embase, Medline, ScienceDirect, and Scopus. They were identified using a search strategy to identify relevant studies that identify oral care interventions for managing mucositis in children with cancer. This study used the Joanna Briggs Institute (JBI) critical appraisal tools to assess the quality of the studies and followed the recommended reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
UNASSIGNED: Eight studies met the inclusion criteria, including seven RCTs and one quasi-experimental study. Oral care interventions involving tooth brushing, mouthwash, and lip care are performed entirely or partially. The frequency of oral care ranges from two to six times daily, and the duration of intervention is from 5 days to six weeks. Oral care interventions using honey, olive oil, Aloe Vera, Andiroba, and salivary enzyme toothpaste are beneficial to lower the severity of mucositis, reduce pain, minimize mucositis duration, and reduce the use of analgesics, but not significantly improve the child\'s quality of life. However, Caphosol mouthwash did not significantly reduce mucositis.
UNASSIGNED: Our study highlights that oral care intervention using effective agents integratively, including honey, olive oil, Aloe vera, Andiroba, and salivary enzyme toothpaste, is essential to manage chemotherapy-induced mucositis among children.
UNASSIGNED: PROSPERO registration number was CRD42023456278.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Osseointegrated dental implants replace missing teeth and create an artificial surface for biofilms of complex microbial communities to grow. These biofilms on implants and dental surfaces can trigger infection and inflammation in the surrounding tissue. This study investigated the microbial characteristics of peri-implant mucositis (PM) and explored the correlation between microbial ecological imbalance, community function, and disease severity by comparing the submucosal microflora from PM with those of healthy inter-subject implants and intra-subject gingivitis (G) within a group of 32 individuals. We analyzed submucosal plaques from PM, healthy implant (HI), and G sites using metagenome shotgun sequencing. The bacterial diversity of HIs was higher than that of PM, according to the Simpson index. Beta diversity revealed differences in taxonomic and functional compositions across the groups. Linear discriminant analysis of the effect size identified 15 genera and 37 species as biomarkers that distinguished PM from HIs. Pathways involving cell motility and protein processing in the endoplasmic reticulum were upregulated in PM, while pathways related to the metabolism of cofactors and vitamins were downregulated. Microbial dysbiosis correlated positively with the severity of clinical inflammation measured by the sulcus bleeding index (SBI) in PM. Prevotella and protein processing in the endoplasmic reticulum also correlated positively with the SBI. Our study revealed PM\'s microbiological and functional traits and suggested the importance of certain functions in disease severity.IMPORTANCEPeri-implant mucositis is an early stage in the progression of peri-implantitis. The high prevalence of it has been a threat to the widespread use of implant prosthodontics. The link between the submucosal microbiome and peri-implant mucositis was demonstrated previously. Nevertheless, the taxonomic and functional composition of the peri-implant mucositis microbiome remains controversial. In this study, we comprehensively characterize the microbial signature of peri-implant mucositis and for the first time, we investigate the correlations between microbial dysbiosis, functional potential, and disease severity. With the help of metagenomic sequencing, we find the positive correlations between microbial dysbiosis, genus Prevotella, pathway of protein processing in the endoplasmic reticulum, and more severe mucosal bleeding in the peri-implant mucositis. Our studies offer insight into the pathogenesis of peri-implant mucositis by providing information on the relationships between community function and disease severity.

BACKGROUND: The efficacy of cancer treatments has links to the intestinal microbiome. Mucositis is a dose-limiting intestinal pro-inflammatory side effect of cancer treatments, that increases the risk of diarrhoea, mucositis, and in severe cases, febrile neutropenia.
METHODS: The effect of cancer treatments on Quality of Life (QoL) was assessed using the FACT C questionnaire that included patient wellbeing and gut adverse symptoms (e.g. diarrhoea). Participants rated faecal samples via the Bristol Stool Chart. In addition, bacterial DNA was extracted from faecal samples, sequenced, and taxonomically examined. The incidence / severity of neutropenia was assessed with white blood cell and neutrophil counts. Circulating SCFAs and plasma lipopolysaccharide (LPS) endotoxin levels were recorded and correlated to intestinal mucositis.
RESULTS: Improvement in bowel function, with reduction in constipation and or diarrhoea or absence of significant disturbance to bowel function was recorded in 85% of the participants. One participant developed febrile neutropenia and two developed bowel toxicity during the study, that was unrelated to the test formulation. No significant changes in microbiota alpha- and beta-diversity at the phylum and species levels respectively from baseline to end of study treatment was observed. None of the participants had raised plasma-endotoxin levels from baseline to the first and subsequent treatment cycles for their cancers. Probiotics in this cohort were deemed safe and tolerable. Significant improvement in emotional QoL scores (p = 0.015) was reported with increased number of chemotherapy cycles. In a related observational study of exceptional responders to chemotherapy, participants were found to have had a high intake of fruits, vegetables, and fibre possibly indicative of a more balanced intestinal microbiota.
CONCLUSIONS: A multi-strain probiotic formulation was safe and tolerated in this chronically ill cohort that were undergoing oncological treatment. The probiotic formulation alleviated diarrhoea, constipation and maintained stool consistency/frequency during the multiple treatments with chemotherapy and radiotherapy. Intestinal dysbiosis that is characterised by decreased microbial diversity and increased pro-inflammatory species was not observed. Probiotic supplementation may have helped reduce dysbiosis during cancer treatments. These improvements may have been critical with the observation that emotional wellbeing was significantly improved from baseline. Hence albeit that the study had limitations, the probiotic intervention provided adjunctive treatment support to the patients. What is of scientifically plausible interest is that probiotics have a long association historically with human hosts and as such ratify their inclusion offering a significant adjunctive therapeutic potential. Future studies warrant larger sample sizes, control groups and should limit recruitment to a largely homogenous group of patients.

OBJECTIVE: This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases.
METHODS: A cohort of 29 patients with a total of 76 implants was included in this study and subsequently divided into three groups based on peri-implant clinical parameters and radiographic examination: healthy (peri-implant health) (n = 29), mucositis (n = 22), and peri-implantitis (n = 25) groups. The levels of ET-1 (ρg/site) and interleukin (IL)-1β (ρg/site) in peri-implant sulcus fluid (PISF) samples were determined using enzyme immunoassay. Statistical analyses were conducted using Kruskal-Wallis and Steel-Dwass tests. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of the biomarkers.
RESULTS: ET-1 levels were significantly elevated in the peri-implantitis group compared to those in the healthy group, and were highest in the peri-implant mucositis group. Additionally, IL-1β levels were significantly higher in the peri-implantitis group than those in the healthy group. ROC curve analysis indicated that ET-1 exhibited superior area under the curve values, sensitivity, and specificity compared to those of IL-1β.
CONCLUSIONS: Our findings suggest that the presence of ET-1 in PISF plays a role in peri-implant diseases. Its significantly increased expression in peri-implant mucositis indicates its potential for enabling earlier and more accurate assessments of peri-implant inflammation when combined with conventional examination methods.