Microbes exploit death-induced nutrient release by gut epithelial cells.

Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis1. Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract2. A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component3-6, but the direct effect of dying mammalian cells on bacterial growth is unclear. Here we advance a concept that several Enterobacteriaceae, including patient-derived clinical isolates, have an efficient growth strategy to exploit soluble factors that are released from dying gut epithelial cells. Mammalian nutrients released after caspase-3/7-dependent apoptosis boosts the growth of multiple Enterobacteriaceae and is observed using primary mouse colonic tissue, mouse and human cell lines, several apoptotic triggers, and in conventional as well as germ-free mice in vivo. The mammalian cell death nutrients induce a core transcriptional response in pathogenic Salmonella, and we identify the pyruvate formate-lyase-encoding pflB gene as a key driver of bacterial colonization in three contexts: a foodborne infection model, a TNF- and A20-dependent cell death model, and a chemotherapy-induced mucositis model. These findings introduce a new layer to the complex host-pathogen interaction, in which death-induced nutrient release acts as a source of fuel for intestinal bacteria, with implications for gut inflammation and cytotoxic chemotherapy treatment.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.

The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.

Population pharmacokinetics of posaconazole in allogeneic haematopoietic stem cell transplant patients.

BACKGROUND: Invasive fungal disease (IFD) in the early post-allogeneic HSCT (alloHCT) period is associated with increased likelihood of catastrophic outcomes. The utility of oral modified release (MR) posaconazole tablets is limited by reduced drug absorption from gastrointestinal toxicity induced by cytotoxic chemotherapy, necessitating a switch to the IV posaconazole formulation. OBJECTIVES: To describe the population pharmacokinetics of posaconazole for oral MR and IV formulations in alloHCT patients and determine dosing regimens likely to achieve therapeutic exposures. METHODS: We performed a prospective observational pharmacokinetic study in adult patients in the early post-alloHCT period requiring a change in posaconazole formulation (oral to IV). Samples were analysed using a validated LC-MS/MS method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. RESULTS: Twenty patients aged between 21 and 70 years were included in the study. A two-compartment model, incorporating mucositis/diarrhoea to modify the bioavailability for oral administration best described the data. To achieve ≥90% PTA, simulations showed that higher than currently recommended doses of oral MR posaconazole were required for prophylaxis Cmin targets (≥0.5 and ≥0.7 mg/L), while increased doses of both formulations were required for IFD treatment PK/PD targets, with patients experiencing oral mucositis/diarrhoea unlikely to achieve these. CONCLUSIONS: Increased doses of posaconazole should be considered for both prophylaxis and treatment of IFD to increase the proportion of alloHCT patients achieving therapeutic exposures, particularly the oral formulation in patients with mucositis and/or diarrhoea. Posaconazole therapeutic drug monitoring should be considered for all formulations in this setting.

The applicability of the central line-associated bloodstream infection (CLABSI) criteria for the evaluation of bacteremia episodes in pediatric oncology patients.

BACKGROUND: The aim of this study was to investigate the applicability of the central line-associated bloodstream infection (CLABSI) criteria of the Centers for Disease Control and Prevention in pediatric oncology patients. METHODS: Bacteremia episodes from 2020 to 2022 from a prospective cohort of pediatric oncology patients with a central venous catheter were included. Episodes were classified by three medical experts following the CLABSI criteria as either a CLABSI or non-CLABSI (i.e., contamination, other infection source, or mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI)). Subsequently, they were asked if and why they (dis)agreed with this diagnosis following the criteria. The primary outcome was the percentage of episodes where the experts clinically disagreed with the diagnosis given following the CLABSI criteria. RESULTS: Overall, 84 bacteremia episodes in 71 patients were evaluated. Following the CLABSI criteria, 34 (40%) episodes were classified as CLABSIs and 50 (60%) as non-CLABSIs. In 11 (13%) cases the experts clinically disagreed with the diagnosis following the CLABSI criteria. The discrepancy between the CLABSI criteria and clinical diagnosis was significant; McNemar's test p < .01. Disagreement by the experts with the CLABSI criteria mostly occurred when the experts found an MBI-LCBI a more plausible cause of the bacteremia than a CLABSI due to the presence of a gram negative bacteremia (Pseudomonas aeruginosa n = 3) and/or mucositis. CONCLUSIONS: A discrepancy between the CLABSI criteria and the evaluation of the experts was observed. Adding Pseudomonas aeruginosa as an MBI pathogen and incorporating the presence of mucositis in the MBI-LCBI criteria, might increase the applicability.

Spectroscopic insights into peri-implant mucositis and peri-implantitis: unveiling peri-implant crevicular fluid profiles using surface enhanced Raman scattering.

The precise identification and differentiation of peri-implant diseases, without the need for intrusive procedures, is crucial for the successful clinical treatment and overall durability of dental implants. This work introduces a novel approach that combines surface-enhanced Raman scattering (SERS) spectroscopy with advanced chemometrics to analyse peri-implant crevicular fluid (PICF) samples. The primary purpose is to offer an unbiased evaluation of implant health. A detailed investigation was performed on PICF samples obtained from a cohort of patients exhibiting different levels of peri-implant health, including those with healthy implants, implants impacted by peri-implantitis, and implants with peri-implant mucositis. The obtained SERS spectra were analysed using canonical-powered partial least squares (CPPLS) to identify unique chemical characteristics associated with each inflammatory state. Significantly, our research findings unveil the presence of a common inflammatory SERS spectral pattern in cases of peri-implantitis and peri-implant mucositis. Furthermore, the SERS-based scores obtained from CPPLS were combined with established clinical scores and subjected to a linear discriminant analysis (LDA) classifier. Repeated double cross-validation was used to validate the method's capacity to discriminate different implant conditions. The integrated approach showcased high sensitivity and specificity and an overall balanced accuracy of 92%, demonstrating its potential to serve as a non-invasive diagnostic tool for real-time implant monitoring and early detection of inflammatory conditions.

Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.

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.

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity.

PURPOSE: 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. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

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.

Clinical, immunological and microbiological evaluation of experimental peri-implant mucositis and gingivitis in subjects with Grade C, stage III/IV periodontitis background.

AIM: To compare individuals with a periodontitis background (Grade C, stage III/IV-formerly generalized aggressive periodontitis) (H-GAP) with periodontally healthy subjects (H-Health) in terms of molecular changes (immunological/microbiological) accompanying experimental peri-implant mucositis and gingivitis. MATERIALS AND METHODS: H-GAP and control (H-Health) subjects were recruited, and experimental mucositis/gingivitis was induced around a single screw-retained implant and one contralateral tooth. Participants refrained from oral hygiene for 21 days in the selected areas, followed by professional prophylaxis and hygiene instructions for 21 days. Clinical parameters, immunological markers (multiplex analysis) and microbial data (16S rRNA gene sequencing) were collected at baseline, during induction (7, 14 and 21 days) and following remission (42 days). RESULTS: Clinically, no significant differences were observed between the groups (n = 10/each group) (H-GAP vs. H-Health) (p > .05, Mann-Whitney test) and the type of site (tooth vs. implant) (p > .05, Wilcoxon test) at the time of onset and resolution, or severity of gingival/mucosal inflammation. H-GAP displayed lower concentrations of the cytokines interleukin (IL)-1B, IL-4, IL-17, tumor necrosis factor-α and interferon-γ around implants than H-Health at baseline and during induction of mucositis (p < .05, Mann-Whitney test). In both groups, implants showed significantly higher inflammatory background at baseline and all subsequent visits when compared with teeth (p < .05, Wilcoxon test). Alpha and ß-diversity metrics showed a significant shift in the microbiome composition and abundances of core species during induction and resolution of peri-implant mucositis and gingivitis (p < .05, restricted maximum likelihood method of Shannon and Bray-Curtis indices, respectively). Differences were not significant for these parameters between the H-Health and H-GAP groups when the periodontal and peri-implant microbiomes were compared separately; however, at each time point, the peri-implant microbiome differed significantly from the periodontal microbiome. CONCLUSIONS: Within the limitations of this pilot study (e.g. low power), it can be concluded that different microbial shifts contribute to the onset and progression of inflammatory responses around teeth and implants and that history of periodontal disease experience plays an additional role in modulating the immune response of peri-implant and periodontal tissues to biofilm accumulation.

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.

Chemotherapeutic metabolism presenting as a recalcitrant case of hand-foot syndrome and mucositis.

INTRODUCTION: Mercaptopurine (6MP) and methotrexate (MTX) are commonly used for maintenance chemotherapy for acute lymphoblastic leukemia (ALL). These medications have been associated with various side effects such as myelosuppression, colitis, and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects most reported include mucositis, alopecia, xerosis, and pruritus. We report an interesting case of hand-foot syndrome to 6MP in a child on maintenance therapy for B-cell ALL from an alteration in medication metabolism. CASE: We report a 10-year-old male on maintenance chemotherapy for pre-Bcell ALL who presented to the hospital with worsening oral lesions and erythematous, fissured plaques on the palms and soles. Maintenance therapy consisted of IV vincristine and 5-day pulse of steroids every 12 weeks, daily 6MP, and weekly MTX, which were increased to ≥ 150% of standard dosing due to persistent absolute neutrophil counts > 1500. Metabolites obtained on admission demonstrated elevated 6MMP metabolites at 35,761 (normal < 5700). TPMT and NUDT15 enzyme activity were normal and no alterations in genotyping were discovered. OUTCOME: Patient's oral chemotherapy, including both 6MP and MTX, were stopped and allopurinol 100 mg daily was initiated, which lead to overall improvement. DISCUSSION: Clinical findings of acute mucositis and worsening of hand-foot syndrome, in the setting of inadequate myelosuppression in a child on maintenance therapy for ALL should raise concerns to consider altered metabolism pathway leading to toxic metabolite buildup. Allopurinol can play in improving cutaneous manifestation and chemotherapeutic dosing in patients with altered metabolism.

Severe reactive infectious mucocutaneous eruption mimicking drug-induced epidermal necrolysis triggered by norovirus.

Reactive infectious mucocutaneous eruption (RIME) is an eruptive mucositis with varying degrees of cutaneous involvement presumed to be due to an immunologic response to various infectious pathogens. Most reported cases occur after a prodromal upper respiratory illness. We present a patient with a particularly severe case mimicking drug-induced epidermal necrolysis found to be triggered by asymptomatic norovirus infection, a virus not previously reported in association with RIME.

Distal toxic acral erythema and mucositis secondary to 6-mercaptopurine in a thiopurine methyltransferase "super shunter".

Toxic erythema of chemotherapy is a broad but useful diagnosis used to summate the non-infectious, non-allergic, and reproducible reaction of certain chemotherapeutics. Due to overlapping chemotherapy side effects and often multiple drug exposures, identification of a singular culprit drug is challenging for dermatologists. Herein, we report a patient with 6-mercaptopurine (6-MP) toxic erythema confirmed via toxic metabolite markers secondary to increased levels of thiopurine methyltransferase activity, or so called "super shunting." Consulting dermatologists should be aware of "super shunting" in pediatric patients and consider testing for metabolites in patients with toxic acral erythema and mucositis in the setting of 6-MP.

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.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

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.

An exploratory study of a multi-species probiotic formulation and markers of health in a real-world oncological cohort in the time of covid.

INTRODUCTION: 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. CONCLUSION: 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.

Fermented foods and probiotic consumption frequency as protective indicators for peri-implant diseases - a cross-sectional study.

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. CONCLUSION: 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.

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.

Evaluation of the efficacy of inter-dental brush and dental floss for peri-implant mucositis: A crossover randomized clinical trial.

OBJECTIVES: To evaluate the most effective method for mechanical inter-dental plaque removal between inter-dental brushes (IDB) and dental floss (DF), in addition to toothbrushing in patients affected by peri-implant mucositis (PIM); to identify possible factors related to the patient or to the single implant-supported element that could influence plaque accumulation and inflammation of peri-implant tissues. METHODS: Forty patients with PIM were recruited. They were randomly assigned to two different groups depending on inter-dental device used (IDB or DF). At baseline (T0), interproximal area (IA), interproximal emergence angle of the implant crown (A°) and manual dexterity (evaluated with Purdue Pegboard) have been recorded. At 14 days (T1), the inter-dental cleaning devices have been inverted between groups. After 14 days (T2), the Plaque Index (PI) and Gingival Index (GI) have been recorded. A questionnaire has been submitted to a patient for the analysis of preferences at T0, T1 and T2. RESULTS: Both inter-dental cleaning devices were effective in reducing PI and GI in the inter-dental area after 14 days of use. GI reduction was influenced by manual dexterity of the dominant hand. No significant differences were found for PI and GI at the variation of IA and A°. CONCLUSION: IDB was the most effective method for inter-dental plaque removal in all subjects regardless of their manual dexterity. DF seems to be more effective than IDB only in subjects with good dexterity.

Dose- and time-dependent association of smoking and its cessation with risk of peri-implant diseases.

DESIGN: A retrospective cohort study involved patients who received at least one implant-supported restoration at a university dental clinic between 2001 and 2013. Patients were randomly selected from an electronic database, and their recruitment via telephone contact spanned from February 2021 until July 2021. MAIN OBJECTIVE: To investigate the association of smoking and its cessation with the risk of peri-implant mucositis and peri-implantitis in a cohort of implant-treated patients. METHODS: The study adhered to the principles outlined in the Declaration of Helsinki and followed the STROBE guidelines for reporting observational research. Included were adult patients who were rehabilitated with dental implants, irrespective of the type of edentulism, superstructure, and prosthetic retention, provided that they had adequate access for peri-implant probing. Patients with incomplete records were excluded. Clinical measurements included plaque and bleeding indices, periodontal pocket depth, suppuration on probing, mucosal recession, and width of keratinized mucosa. Periapical radiographs were taken and marginal bone level (MBL) was measured using ImageJ software. The primary outcome variable was peri-implant status which was classified into: health (H), peri-implant mucositis (PM), and peri-implantitis (PI). Smoking status was categorized into: never-smokers, former smokers, and current smokers. Smoking information included: daily cigarette consumption, duration of smoking (in years), and age at initiation, and for former smokers, the duration of smoking cessation. RESULTS: The cohort included 117 patients (55 females and 62 males) with a mean age of 64.2 years at examination. They were rehabilitated by 450 implants, with an average of 4.6 implants per patient and a mean duration of 8 years in function. Out of the total, 39 patients were H, while 41 and 37 showed PM and PI, respectively. Periodontal and MBL measures were significantly higher in PM and PI groups compared to H group (p < 0.001). Considering tobacco use, 56 patients were never-smokers, 42 former smokers, and 19 current smokers. The average daily consumption of cigarettes was 15.7. Ever-smokers >23 pack-years had a significantly higher risk for PI (OR = 3.40; 95% CI 0.91-17.30; p = 0.002) compared to nonsmokers. Regression analysis showed that subjects with a span since smoking cessation of more than 21 years exhibited a significantly lower risk of peri-implant diseases (PIDs) than those who had ceased smoking within 21 years (p = 0.028). CONCLUSION: A smoking intensity exceeding 23 pack-years was significantly associated with PI risk, while the risk of PIDs was comparable between never-smokers and those who had quit smoking more than 21 years ago.