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Background: The present observational clinical investigation is based on the hypothesis that subgingival yeast carriage (SYC) is higher in cigarette-smokers with peri-implant mucositis (PM) than non-smokers with and without PM., Objective: The aim was to assess peri-implant clinical profile and SYC among cigarette-smokers with PM., Methodology: Participants were divided into four groups: Group-1-Cigarette-smokers with PM; Group-2-Cigarette-smokers without PM; Group-3-Non-smokers with PM; and Group-4-Non-smokers without PM. Information on duration and daily frequency of cigarette smoking (pack years), age, gender, familial history of smoking and most recent visit to a dentist and/or dental hygienist was collected. The following information was retrieved from healthcare records: implant dimensions, implant insertion torque, depth of insertion (credidastal or subcrestal), implant abutment connection, jaw location, implant surface characteristic, and mode of implant prosthesis retention. Peri-implant modified plaque and gingival indices (mPI and mGI), probing depth (PD) and crestal bone loss were recorded. Subgingival biofilm samples were collected, and SYC was recorded in colony forming units per milliliter (CFU/ml). P < 0.05 were considered statistically significant., Results: Eighty male individuals (20, 19, 21 and 20 individuals were included in groups 1, 2, 3 and 4, respectively) were included. The mPI was higher in Group-1 than groups 2 (P < 0.05) and 4 (P < 0.05). The mPI was higher in Group-3 than groups 2 (P < 0.05) and 4 (P < 0.05). The mGI was higher in Group-3 than groups 1 (P < 0.05), 2 (P < 0.05) and 4 (P < 0.05). The PD was higher in Group-1 than groups 2 (P < 0.05) and 4 (P < 0.05). The PD was higher in Group-3 than Groups 2 (P < 0.05) and 4 (P < 0.05). The CFU/ml were higher in Group-1 than groups 2 (P < 0.05) and 4 (P < 0.05). The CFU/ml were higher in Group-3 than groups 2 (P < 0.05) and 4 (P < 0.05)., Conclusion: Peri-implant soft-tissue inflammatory parameters are worse and SYC is higher in moderate smokers than light smokers with PM and non-smokers without PM., (© 2024. The Author(s).)

Purpose: To describe the emerging evidence concerning etiologic factors and pathophysiologic mechanisms involved in peri-implant inflammatory diseases., Materials and Methods: An electronic search for articles published until November 2022 was conducted in MEDLINE by three independent reviewers to identify the manuscripts' reporting data on etiologic factors and pathophysiologic mechanisms associated with peri-implant diseases., Results: Current evidence suggests that peri-implant mucositis and peri-implantitis are inflammatory conditions linked to a microbial challenge. However, in recent years there has been increasing evidence indicating that certain peri-implant inflammatory conditions may not be primarily related to biofilm-mediated infectious processes but rather to other biologic mechanisms, such as a foreign body response., Conclusions: Current evidence in the dental and medical literature opens new avenues for a more complex interpretation of the etiopathogenetic factors involved in peri-implant diseases. A better understanding of various factors related to the host response, including dysbiosis mechanisms associated with changes in microbiota composition, is necessary for a more precise physiopathologic characterization of these diseases.

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., (© 2024. The Author(s).)

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., Competing Interests: The authors declare no conflict of interest.

Purpose of Review: Disruption of the precious ecosystem of micro-organisms that reside in the gut - the gut microbiota - is rapidly emerging as a key driver of the adverse side effects/toxicities caused by numerous anti-cancer agents. Although the contribution of the gut microbiota to these toxicities is understood with ever increasing precision, the cause of microbial disruption (dysbiosis) remains poorly understood. Here, we discuss current evidence on the cause(s) of dysbiosis after cancer therapy, positioning breakdown of the intestinal mucosa (mucositis) as a central cause., Recent Findings: Dysbiosis in people with cancer has historically been attributed to extensive antibiotic use. However, evidence now suggests that certain antibiotics have minimal impacts on the microbiota. Indeed, recent evidence shows that the type of cancer therapy predicts microbiota composition independently of antibiotics. Given most anti-cancer drugs have modest effects on microbes directly, this suggests that their impact on the gut microenvironment, in particular the mucosa, which is highly vulnerable to cytotoxicity, is a likely cause of dysbiosis. Here, we outline evidence that support this hypothesis, and discuss the associated clinical implications/opportunities., Summary: The concept that mucositis dictates microbiota compositions provides two important implications for clinical practice. Firstly, it reiterates the importance of prioritising the development of novel mucoprotectants that preserve mucosal integrity, and indirectly support microbial stability. Secondly, it provides an opportunity to identify dysbiotic events and associated consequences using readily accessible, minimally invasive biomarkers of mucositis such as plasma citrulline., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chemotherapy-induced intestinal mucositis is one of the major toxic side effects in the treatment of cancer patients. The purpose of this study is to screen lactic acid bacteria which could alleviate intestinal inflammation and damage induced by chemotherapeutic agents and explore the possible underlying mechanisms. Lactobacillus salivarius CPU-01 was selected from traditional Chinese fermented foods due to its protective effects on the toxicity of temozolomide in Caenorhabditis elegans. Eighteen ICR mice were randomly divided into 3 groups including control group, temozolomide-induced intestinal mucositis group, and temozolomide + L. salivarius CPU-01 group, and were used to investigate the effect of L. salivarius CPU-01 on chemotherapy-induced intestinal mucositis. It has been demonstrated that the administration of L. salivarius CPU-01 can prevent colon shortening and alleviate colon tissue damage caused by temozolomide-induced intestinal mucositis in mice. L. salivarius CPU-01 relieved the intestinal microbiota disorders caused by temozolomide and contributed to the growth of beneficial bacteria, such as Lactobacillus, Clostridia UCG - 014&#95;norank, and Akkermansia. In vivo experiments also indicated that L. salivarius CPU-01 can suppress the level of temozolomide-induced pro-inflammatory cytokines in serum and mRNA expression in the small intestine tissues. It was also found that L. salivarius CPU-01 significantly increased the expressions of intestinal tight junction (TJ) proteins, ZO-1, and Occludin proteins in mice treated with temozolomide. These findings suggest that L. salivarius CPU-01 can ameliorate temozolomide-induced intestinal mucositis by modulating gut microbiota, blocking pro-inflammatory cytokines, and repairing the intestinal barrier. These findings suggest probiotics may serve as a potential alternative therapeutic strategy for the prevention of chemotherapy-induced intestinal mucositis in the future., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to investigate the relationship between microbial communities and the severity of peri-implant mucosal bleeding in peri-implant mucositis., Materials and Methods: Submucosal plaque samples were collected from 54 implants divided into the healthy implant (HI) group, peri-implant mucositis (PM) group, and peri-implantitis (PI) group. Sequencing of 16S rRNA was performed using the Illumina MiSeq platform. Alpha diversity (i.e., Shannon and Chao index) and beta diversity were used to measure microbial diversity within and between microbial communities, respectively. Differences in microbial taxa between groups were assessed via linear discriminate analysis effect size. Correlation between the modified sulcus bleeding index (mSBI) and microbial dysbiosis index (MDI) was examined using Spearman correlation analysis and linear models., Results: The submucosal bacterial richness (Chao index) was positively correlated with the mean mSBI in the PM group. As the mean mSBI increased in the PM group, the beta diversity became closer to that of the PI group. In the PM group, the abundances of 47 genera were significantly correlated with the mean mSBI, and the MDI was positively associated with the mean mSBI. Fourteen of the forty-seven genera were discriminative taxa between the HI and PI groups, and the abundances of these biomarkers became closer to those in the PI group in the progression of peri-implant disease., Conclusions: A higher mSBI value corresponded to a higher risk of microbial dysbiosis in peri-implant mucositis. The biomarkers identified may be useful for monitoring the progression of peri-implant disease., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This systematic review evaluated the features of the progression of experimentally induced gingivitis and peri-implant mucositis in humans. Included were studies that evaluated clinical, immunological, or microbiological responses between experimentally induced gingivitis and peri-implant mucositis in periodontally healthy patients. A total of 887 articles were initially identified, but only 12 were included in the final analysis. Implants accumulate less biofilm and suffer the most heterogeneous alterations in the microbiota, in the abstinence of oral hygiene, compared with the tooth. Interestingly, although dental implants presented less biofilm accumulation, the peri-implant mucosa showed a more exacerbated clinical response than the gingival tissue. The risk of bias of the selected studies was moderate to low, with one study presenting serious risk. The progression events of peri-implant mucositis were similar to those of experimental gingivitis but led to a different host response. This review was registered in the PROSPERO database CRD420201 123360.

Although bacteria-free DNA in blood during systemic infection is mainly derived from bacterial death, translocation of the DNA from the gut into the blood circulation (gut translocation) is also possible. Hence, several mouse models with experiments on macrophages were conducted to explore the sources, influences, and impacts of bacteria-free DNA in sepsis. First, bacteria-free DNA and bacteriome in blood were demonstrated in cecal ligation and puncture (CLP) sepsis mice. Second, administration of bacterial lysate (a source of bacterial DNA) in dextran sulfate solution (DSS)-induced mucositis mice elevated blood bacteria-free DNA without bacteremia supported gut translocation of free DNA. The absence of blood bacteria-free DNA in DSS mice without bacterial lysate implies an impact of the abundance of bacterial DNA in intestinal contents on the translocation of free DNA. Third, higher serum cytokines in mice after injection of combined bacterial DNA with lipopolysaccharide (LPS), when compared to LPS injection alone, supported an influence of blood bacteria-free DNA on systemic inflammation. The synergistic effects of free DNA and LPS on macrophage pro-inflammatory responses, as indicated by supernatant cytokines (TNF-α, IL-6, and IL-10), pro-inflammatory genes ( NFκB , iNOS , and IL-1β ), and profound energy alteration (enhanced glycolysis with reduced mitochondrial functions), which was neutralized by TLR-9 inhibition (chloroquine), were demonstrated. In conclusion, the presence of bacteria-free DNA in sepsis mice is partly due to gut translocation of bacteria-free DNA into the systemic circulation, which would enhance sepsis severity. Inhibition of the responses against bacterial DNA by TLR-9 inhibition could attenuate LPS-DNA synergy in macrophages and might help improve sepsis hyper-inflammation in some situations.

Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 5 1A in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 5 1A at a concentration of 1 × 10 9 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 5 1A increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 5 1A reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 5 1A protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Acute intestinal mucositis is a common off-target effect of chemotherapy, leading to co-morbidities such as vomiting, diarrhea, sepsis, and death. We previously demonstrated that the presence of enteric bacteria modulates the extent of jejunal epithelial damage induced by doxorubicin (DXR) in mice. Despite conventional thinking of the crypt as a sterile environment, recent evidence suggests that bacterial signaling influences aISC function. In this study, we labeled aISCs using transgenic Lgr5 -driven fluorescence or with immunostaining for OLFM4. We examined the effect of DXR in both germ free (GF) mice and mice depleted of microbiota using an established antimicrobial treatment protocol (AMBx). We found differences in DXR-induced loss of aISCs between GF mice and mice treated with AMBx. aISCs were decreased after DXR in GF mice, whereas AMBx mice retained aISC expression after DXR. Neither group of mice exhibited an inflammatory response to DXR, suggesting the difference in aISC retention was not due to differences in local tissue inflammation. Therefore, we suspected that there was a protective microbial signal present in the AMBx mice that was not present in the GF mice. 16S rRNA sequencing of jejunal luminal contents demonstrated that AMBx altered the fecal and jejunal microbiota. In the jejunal contents, AMBx mice had increased abundance of Ureaplasma and Burkholderia . These results suggest pro-survival signaling from microbiota in AMBx-treated mice to the aISCs, and that this signaling maintains aISCs in the face of chemotherapeutic injury. Manipulation of the enteric microbiota presents a therapeutic target for reducing the severity of chemotherapy-associated mucositis.

Background: Mycoplasma pneumoniae atypical pneumonia is frequently associated with erythema multiforme. Occasionally, a mycoplasma infection does not trigger any cutaneous but exclusively mucosal lesions. The term mucosal respiratory syndrome is employed to denote the latter condition. Available reviews do not address the possible association of mucosal respiratory syndrome with further atypical bacterial pathogens such as Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella species. We therefore performed a systematic review of the literature addressing this issue in the National Library of Medicine, Excerpta Medica, and Web of Science databases., Summary: We found 63 patients (≤18 years, n = 36; >18 years, n = 27; 54 males and 9 females) affected by a mucosal respiratory syndrome. Fifty-three cases were temporally associated with a M. pneumoniae and 5 with a C. pneumoniae infection. No cases temporally associated with C. psittaci, C. burnetii, F. tularensis, or Legionella species infection were found. Two cases were temporally associated with Epstein-Barr virus or influenzavirus B, respectively., (© 2021 S. Karger AG, Basel.)

Mucositis is defined as inflammatory and/or ulcerative lesions of the oral and/or gastrointestinal tract. It occurs in approximately 40% to 50% of adults patients receiving conventional chemotherapy and up to 75% of patients receiving high dose chemotherapy as conditioning for hematopoietic stem cell transplantation. It is a toxic side effect, which strongly impairs quality of life and leads to refractory pain, increasing risk of infection and even therapeutic modifications. Despite improvements made, the management of mucositis remains a challenge and is still not consensual. A multicentric survey of practices concerning the preventive and curative management of chemo-induced mucositis in pediatric oncology department in France was carried out using a standardized questionnaire. Results confirm heterogeneous practices and the small progress made during the last decade. This national survey and an analysis of the recent literature leads to propose guidelines for the prevention and treatment of oral mucositis in children receiving treatment for cancer., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: 16S sequencing results are often used for Machine Learning (ML) tasks. 16S gene sequences are represented as feature counts, which are associated with taxonomic representation. Raw feature counts may not be the optimal representation for ML., Methods: We checked multiple preprocessing steps and tested the optimal combination for 16S sequencing-based classification tasks. We computed the contribution of each step to the accuracy as measured by the Area Under Curve (AUC) of the classification., Results: We show that the log of the feature counts is much more informative than the relative counts. We further show that merging features associated with the same taxonomy at a given level, through a dimension reduction step for each group of bacteria improves the AUC. Finally, we show that z-scoring has a very limited effect on the results., Conclusions: The prepossessing of microbiome 16S data is crucial for optimal microbiome based Machine Learning. These preprocessing steps are integrated into the MIPMLP - Microbiome Preprocessing Machine Learning Pipeline, which is available as a stand-alone version at: https://github.com/louzounlab/microbiome/tree/master/Preprocess or as a service at http://mip-mlp.math.biu.ac.il/Home Both contain the code, and standard test sets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jasner, Belogolovski, Ben-Itzhak, Koren and Louzoun.)

Aims: To evaluate a mixture of selected lactic acid bacteria (LAB) (a riboflavin-producer, a folate-producer and an immunomodulatory strain) as co-adjuvant for 5-fluorouracil (5-FU) chemotherapy in cell culture and using a 4T1 cell animal model of breast cancer., Methods and Results: The viability of Caco-2 cells exposed to 5-FU and/or LAB was analysed. Mice bearing breast tumour were treated with 5-FU and/or LAB. Tumour growth was measured. Intestinal mucositis (IM) was evaluated in small intestine; haematological parameters and plasma cytokines were determined. The bacterial mixture did not negatively affect the cytotoxic activity of 5-FU on Caco-2 cells. The LAB mixture attenuated the IM and prevented blood cell decreases associated with 5-FU treatment. Mice that received 5-FU and LAB mixture decreased tumour growth and showed modulation of systemic cytokines modified by both tumour growth and 5-FU treatment. The LAB mixture by itself delayed tumour growth., Conclusions: The mixture of selected LAB was able to reduce the side-effects associated with chemotherapy without affecting its primary anti-tumour activity., Significance and Impact of the Study: This bacterial mixture could prevent the interruption of conventional oncologic therapies by reducing undesirable side-effects. In addition, this blend would provide essential nutrients (vitamins) to oncology patients., (© 2020 The Society for Applied Microbiology.)

Colorectal cancer (CRC) has become a serious threat to human life and health. Most patients are diagnosed at the late stage of advanced CRC, resulting in losing their best opportunity for surgical treatment. Chemotherapy plays a crucial role in the control and treatment of advanced CRC. However, the cytotoxicity of chemotherapeutic drugs can easily cause the imbalance of gut flora, damage the barrier of the gastrointestinal mucosa, and mediate mucosal inflammation of the digestive tract, which is called "gastrointestinal mucositis." This mucositis can affect the quality of life of the host and even threaten their lives. Several studies reported the association between chemotherapy-mediated gastrointestinal mucositis in CRC and gut dysbiosis. However, the underlying mechanisms of this association are still unclear. The alternative or complementary treatments to reshape gut microbiota and slow down the side effects of chemotherapy have shown the improvement of gastrointestinal mucositis following chemotherapy in the CRC condition. This review will summarize and discuss the evidence of the association between chemotherapy-mediated gastrointestinal mucositis in CRC and altered gut microbiota from in vivo and clinical studies. The possible mechanisms of gastrointestinal mucositis, including the destruction of the gastrointestinal mucosal barrier, the induction of gut dysbiosis, and histopathological changes in the gut of CRC with chemotherapy will be illustrated. In addition, the nonpharmacological interventions and phytochemical extracts by using the manipulation of the microbial population for therapeutic purposes for relieving side effects of chemotherapy as well as a cancer treatment would be summarized and discussed in this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mycoplasma pneumoniae-induced rash and mucositis is the most accurate diagnosis for patients with blistering mucocutaneous disease provoked by an infection. Recent literature suggests expansion of the name is required, as other infections have caused a clinically similar presentation. This review provides a concise update on current understanding of M. pneumoniae-induced rash and mucositis and other reactive infectious mucocutaneous eruptions., (© 2020 British Association of Dermatologists.)

Background: 5-Fluorouracil (5-FU)-based chemotherapy is first-line chemotherapy for colorectal cancer. However, 5-FU-induced intestinal mucositis (FUIIM) is a common adverse effect that severely impairs drug tolerance and results in poor patient health., Methods: Male C57BL/6 mice were given 5-FU (50 mg/kg/day, i.p.) and treated with MPH-966 (5 and 7.5 mg/kg/day, p.o.) for five days. The body weight loss and the amount of food intake, and histopathological findings were recorded and analyzed. In addition, the neutrophil infiltration, levels of neutrophil serine proteases and pro-inflammatory cytokines, and tight junction proteins expression in intestinal tissues were determined. The ecology of gut microbiota was performed through next-generation sequencing technologies., Results: Neutrophil elastase (NE) overexpression is a key feature in FUIIM. This study showed that treatment with the specific NE inhibitor MPH-966 (7.5 mg/kg/day, p.o.) significantly reversed 5-FU-induced loss in body weight and food intake; reversed villous atrophy; significantly suppressed myeloperoxidase, NE, and proteinase 3 activity; and reduced pro-inflammatory cytokine expression in an FUIIM mouse model. In addition, MPH-966 prevented 5-FU-induced intestinal barrier dysfunction, as indicated by the modulated expression of the tight junction proteins zonula occludin-1 and occludin. MPH-966 also reversed 5-FU-induced changes in gut microbiota diversity and abundances, specifically the Firmicutes-to-Bacteroidetes ratio; Muribaculaceae, Ruminococcaceae, and Eggerthellaceae abundances at the family level; and Candidatus Arthromitus abundance at the genus level., Conclusion: These data indicate that NE inhibitor is a key treatment candidate to alleviate FUIIM by regulating abnormal inflammatory responses, intestinal barrier dysfunction, and gut microbiota imbalance., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Mycoplasma pneumoniae pneumonia is sometimes associated with skin or mucous membrane eruptions. Available reviews do not address the association of Chlamydophila pneumoniae pneumonia with skin eruptions. We therefore conducted a systematic review of the literature addressing this issue. The National Library of Medicine, Excerpta Medica, and Web of Science databases were employed., Summary: In two reports, skin lesions and especially urticaria were more common (p < 0.05) in atypical pneumonia caused by C. pneumoniae as compared with M. pneumoniae. We found 47 patients (<18 years, n = 16; ≥18 years, n = 31) affected by a C. pneumoniae atypical pneumonia, which was associated with erythema nodosum, erythema multiforme minus, erythema multiforme majus, isolated mucositis, or cutaneous vasculitis. We also found the case of a boy with C. pneumoniae pneumonia and acute generalized exanthematous pustulosis. We did not find any case of C. pneumoniae respiratory infection associated with either Gianotti-Crosti syndrome, pityriasis lichenoides et varioliformis acuta Mucha-Habermann, or varicella-like skin eruptions., (© 2020 S. Karger AG, Basel.)

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mucositis is a common side-effect of chemotherapy treatment, inducing alterations in the composition of the gut microbiota. Redox active compounds, such as vitamins B2 and C, have been shown to reduce inflammation and enhance the growth of anaerobic bacteria in the gut. We therefore aimed to (1) validate the ability of these compounds to promote bacterial cell growth in vitro, and (2) determine their prophylactic efficacy in a rat model of methotrexate (MTX)-induced mucositis. Bacterial growth curves were performed to assess the growth kinetics of bacteria exposed to Vitamins C and B2 (0.5 mM). Male wistar rats (150-200 g) received vitamins B2 (12 mg/day) and C (50 mg/day) via daily oral gavage (from day -1 to day 10). MTX (45 mg/Kg) was administrated via I.V. injection (N = 4-8/group) on day 0. Body weight, water/food consumption and diarrhea were assessed daily. Blood and faecal samples were collected longitudinally to assess citrulline levels (mucositis biomarker) and gut microbiota composition. Vitamins C/B2 enhanced the in vitro growth of anaerobic bacteria Blautia coccoides and Roseburia intestinalis . Contrarily to vitamin B2, in vivo administration of Vitamin C significantly attenuated clinical symptoms of mucositis. Despite their influence on the composition of the gut microbiota, both vitamins did not modulate the course of MTX-induced mucositis, as accessed by plasma citrulline. Vitamins B2 and C enhanced anaerobic bacterial growth in vitro, however their ability to mitigate MTX-induced mucositis was limited.

Purpose: To evaluate the natural history and ophthalmologic morbidity of Mycoplasma pneumoniae-induced rash and mucositis (MIRM) and propose a treatment algorithm., Design: Retrospective, interventional case series., Methods: Retrospective chart review of all MIRM patients examined by the department of ophthalmology at a tertiary children's hospital. Diagnosis was established clinically concomitant with either positive Mycoplasma pneumoniae IgM or PCR testing from January 1, 2010, until December 31, 2019. The main outcome measures were best-corrected visual acuity, long-term ocular sequelae, and duration and type of ophthalmic intervention., Results: There were 15 patients (10 male and 5 female) aged 10.9 ± 4.2 years who had primary episodes of MIRM; of those, 4 had multiple episodes. All patients required topical steroid treatment, 3 required amniotic membrane transplantation, and 1 patient underwent placement of a sutureless biologic corneal badage device. There were no patients who suffered visual loss, but 1 was left with mild symblephara near the lateral canthus in each eye and 2 others had scarring of the eyelid margins and blepharitis., Conclusions: The ocular morbidity is significantly less in MIRM than in other closely related syndromes such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. However, these patients still require close observation and a low threshold for intervention to avoid permanent ophthalmic sequelae and possible blindness., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Intestinal mucositis is a common side effect of chemotherapy leading to diarrhea, abdominal pain and increased risk of infections. The intestinal microbiota has been recognized as a key regulator of mucosal immune responses. Therefore, we hypothesized that intestinal microbial changes would be associated with enterocyte loss and systemic inflammation during induction treatment for childhood acute lymphoblastic leukemia (ALL). We prospectively included 51 children newly-diagnosed with ALL treated in Denmark in 2015-2018. Plasma C-reactive protein (CRP), plasma citrulline (marker of functional enterocytes mass) measurements and fecal samplings were performed on treatment Days 1, 8, 15, 22 and 29. Moreover, intestinal mucositis was scored by a trained nurse/physician. Fecal samples in patients and 19 healthy siblings were analyzed by 16S rRNA gene sequencing (V3-V4 region). Bacterial alpha diversity was lower in patients compared to siblings. It decreased from Day 1 to Days 8-22 and increased on Day 29. Shannon alpha diversity index was correlated with CRP on Days 15-29 (rho = -0.33-0.49; p < 0.05) and with citrulline on Days 15 and 29 (although with p values <0.06, rho = 0.32-0.34). The abundance of unclassified Enterococcus species (spp.) was correlated with CRP on Days 22-29 (rho = 0.42-0.49; p < 0.009), while the abundance of unclassified Lachnospiraceae spp. was correlated with citrulline on days 8-15 (rho = 0.48-0.62, p < 0.001). Systemic inflammation, enterocyte loss and relative abundance of unclassified Enterococcus spp. reached a peak around Day 15. In conclusion, specific changes in the microbiota were associated with the severity of enterocyte loss and systemic inflammation during chemotherapy., (© 2020 UICC.)

Chemotherapy-induced intestinal mucositis (CIM) is a principal reason for reduced living quality of patients undergoing chemotherapy. Growing evidence showed gut microbiota played an important role in the development of intestinal mucositis. Dihydrotanshinone I (DHTS) is a liposoluble extract of Salvia miltiorrhiza Bunge with many bioactivities. Here we investigated the effect of DHTS on intestinal mucositis induced by 5-fluorouracil and irinotecan in mice. We detected the degree of intestinal mucosal damage and inflammatory response in CIM mice with or without DHTS administration. The body weight and disease activity index (DAI) of mice were monitored each day. H&E staining was used to evaluate pathological damage. The contents of interleukin 6 (IL-6), tumor necrosis factor (TNFα), diacylglycerol (DAO) and triglyceride (TG) in serum were determined by commercial kits. We also investigated the changes of fecal microbiota by 16S rRNA high-throughput sequencing. Spearman correlation analysis was used to evaluate the correlation between fecal microbiota and inflammatory factors. Tax4Funwas performed to infer the potential function of the microbial community. Results showed DHTS significantly reduced DAI, intestinal mucosal damage and inflammatory response in CIM mice by decreasing serum IL-6 and TNFα. In addition, there is an intense correlation between fecal microbiota and inflammatory factors. DHTS efficiently reversed disordered fecal microflora close to normal and increased the abundance of g&#95;&#95;Akkermansia. DHTS also enriched bacterial species which promote butyric acid metabolism or negatively correlated with inflammatory factors. Besides, species enriched by DHTS in fecal microbiota were probably involved in glutamine production and ammonia oxidation. In conclusion, our study provides evidence that DHTS effectively attenuates CIM induced by 5-fluorouracil and irinotecan in mice. Regulation of the composition and function of fecal microbiota probably plays a critical role in the therapeutic effect of DHTS in CIM mice., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing "beneficial" microbes to rescue busulfan induced mucositis., Results: In the current investigation, FMT from AOS-dosed mice improved small intestine function over FMT from control mice through the recovery of gene expression and an increase in the levels of cell junction proteins. FMT from AOS-dosed mice showed superior benefits over FMT from control mice on recipient gut microbiotas through an increase in "beneficial" microbes such as Leuconostocaceae and recovery in blood metabolome. Furthermore, the correlation of gut microbiota and blood metabolites suggested that the "beneficial" microbe Lactobacillales helped with the recovery of blood metabolites, while the "harmful" microbe Mycoplasmatales did not., Conclusion: The data confirm our hypothesis that FMT from a donor with superior microbes leads to a more profound recovery of small intestinal function. We propose that gut microbiota from naturally produced AOS-treated donor may be used to prevent small intestinal mucositis induced by chemotherapeutics or other factors in recipients. Video Abstract.

Background and Aim: Intestinal mucositis remained one of the most deleterious complications in cancer patients undergoing chemotherapy. 5-FU treatment was reported to affect the abundance of gut microbiota and cause mucositis, which might be ameliorated by probiotics. We investigate the potential changes of 5-FU treatment and the modulations of probiotics on gut microbiota in a mouse model., Methods: Male BALB/c mice received either 5-FU or saline (S). They were separated and fed saline, Lactobacillus casei variety rhamnosus (Lcr) and Lactobacillus reuteri DSM 17938 (BG). Lcr and BG were simultaneously administered with 5-FU for 5 days. Stool specimens were collected for DNA extraction and pyrosequenced for bioinformatic analysis., Results: Fecal microbial communities were obviously diverse. Bacteroides and Bacteroidaceae were the most abundant microbiota in FU.BG group while S24&#95;7 was the most in S.S group. At phylum and class levels, abundances of Betaproteobacteria, Erysipelotrichi, Gammaproteobacteria, and Verrucomicrobia were significantly increased in the FU groups. Probiotics supplementation did increase the abundances of Enterobacteriales and Turicibacterales. We demonstrated that probiotics did modulate the abundance and diversity of gut microbiota. Bacterial motility proteins were found enriched and upregulated in the S.BG group. No mortality was noted. No bacterial translocation was found in spleen and blood among the six groups., Conclusion: Gut microbiota of mice undergoing chemotherapy exhibited a distinct disruption in bacterial composition. Probiotic did modulate the abundance and diversity of gut microbiota. This is the first study to analyze the effects and safety of Lactobacillus strains on 5-FU-induced mucositis systematically and assess changes in the intestinal microbiota after probiotic intervention., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Neisseria meningitidis is an inhabitant of the nasopharynx, from which it is transmitted from person to person or disseminates in blood and becomes a harmful pathogen. In this work, we addressed colonization of the nasopharyngeal niche by focusing on the interplay between meningococci and the airway mucus that lines the mucosa of the host. Using Calu-3 cells grown in air interface culture (cells grown with the apical domain facing air), we studied meningococcal colonization of the mucus and the host response. Our results suggested that N. meningitidis behaved like commensal bacteria in mucus, without interacting with human cells or actively transmigrating through the cell layer. As a result, type IV pili do not play a role in this model, and meningococci did not trigger a strong innate immune response from the Calu-3 cells. Finally, we have shown that this model is suitable for studying interaction of N. meningitidis with other bacteria living in the nasopharynx and that Streptococcus mitis , but not Moraxella catarrhalis , can promote meningococcal growth in this model. IMPORTANCE N. meningitidis is transmitted from person to person by aerosol droplets produced by breathing, talking, or coughing or by direct contact with a contaminated fluid. The natural reservoir of N. meningitidis is the human nasopharynx mucosa, located at the back of the nose and above the oropharynx. The means by which meningococci cross the nasopharyngeal wall is still under debate, due to the lack of a convenient and relevant model mimicking the nasopharyngeal niche. Here, we took advantage of Calu-3 cells grown in air interface culture to study how meningococci colonize the nasopharyngeal niche. We report that the airway mucus is both a niche for meningococcal growth and a protective barrier against N. meningitidis infection. As such, N. meningitidis behaves like commensal bacteria and is unlikely to induce infection without an external trigger., (Copyright © 2019 Audry et al.)

Background: Mycoplasma pneumoniae -induced rash and mucositis (MIRM) is a relatively newly recognized clinical entity that typically presents with predominant mucositis accompanied by variable cutaneous involvement 7-9 days after the onset of prodromal symptoms. There are no evidence-based guidelines for treatment, and current standards of care may include supportive therapy, antibiotics, corticosteroids, and intravenous immunoglobulin ., Objective: This case series aims to describe the potential efficacy of cyclosporine A (CsA) in the treatment of MIRM., Methods: The present case series details our use of CsA early in the course of MIRM in 3 pediatric patients., Results: Rapid clinical resolution was observed following CsA therapy., Conclusions: We suggest that early initiation of CsA may be an effective therapeutic option for MIRM.

Mucositis is a common and severe adverse effect of radiotherapy and/or chemotherapy treatments applied to oncologic patients. The development of effective therapies and adjuvant treatments to increase their efficacy and reduce adverse effect is a priority in cancer therapy. Probiotics are non-pathogenic live microorganisms that when ingested in adequate amounts can colonize the intestinal tract promoting the restoration of a healthy gut microbiota and contributing to all its functions including the maintenance of the integrity of the mucosa and the modulation of the immune system. In order to check the possible efficacy and safety of these microorganisms to prevent or ameliorate mucositis' symptoms, we have systematically searched the bibliographic databases MEDLINE (via Pubmed), EMBASE, The Cochrane library, Scopus, Web of science, and Latin American and Caribbean Literature in Health of Sciences (LILACS) using the descriptors "Mucositis", "Probiotics", "Neoplasms", "Humans", and "Clinical Trials". After applying our inclusion and exclusion criteria, 15 studies were accepted for review and critical analysis. Our analysis suggests that a combination of Bifidobacterium longum , Lactobacillus acidophilus , Bifidobacterium breve , Bifidobacterium infantis, and Saccharomyces boulardii could be a good combination of probiotics to reduce incident rates of mucositis or ameliorate its symptoms in chemo or radiotherapy treated patients.

Objectives: To assess in persons aged 70 years or older the microbiological alterations occurring around implants and natural teeth during and after 3 weeks of undisturbed plaque accumulation. Furthermore, to test the predictive value of several markers at baseline for the extent of inflammation around implants and teeth after this period., Materials and Methods: Twenty partially edentulous participants with titanium implants refrained from oral hygiene practices while being clinically monitored in weekly intervals for 21 days. Teeth and implants were then cleaned, oral hygiene resumed, and the participants were further monitored. Levels of six subgingival plaque microorganisms, the plaque index (PI), and the gingival index (GI) were assessed before (baseline), during (days 0, 7, 14, 21), and after plaque accumulation (days 28, 42). Six microorganisms; demographic and clinical variables at day 0 were further evaluated as potential predictors for presence of GI > 1 at days 21 and 28., Results: The detection frequency of the selected bacteria did not differ between implants and teeth at any time point. Bacteria counts decreased in the preparatory phase and increased in the plaque accumulation phase. Patterns observed at implants and teeth were similar. Only Parvimonas micra at day 21 reached significantly higher counts at implants than teeth. For the prediction of clinical outcome at day 21, in the multivariable model, only implant vs. tooth was significant indicator for the primary outcome (p = 0.01)., Conclusions: Overall, the analysis of subgingival/submucosal samples revealed only minor differences between implants and teeth during the development and resolution of inflammation., Clinical Relevance: Within the limitations of our study, with plaque accumulation, elders develop more inflammation around implants than around teeth, in spite of similar bacterial profiles.

Purpose: Mycoplasma pneumoniae is a common cause of pediatric respiratory infections, with a quarter having extrapulmonary complications, most commonly a mucocutaneous eruption involving the ocular surface. A detailed description of the ophthalmic manifestations in Mycoplasma-induced rash and mucositis (MIRM) is currently lacking in the scientific literature., Methods: This is a retrospective chart review of consecutive cases of MIRM at a tertiary referral children's hospital between October 1 and December 1, 2018, with up to 2 months of follow-up. Main outcomes and measures were demographic information, clinical examination findings including visual acuity, detailed anterior segment findings, and course of both ophthalmic and systemic disease., Results: Five patients were included. Age range was 8 to 17 years (mean age 11.9 years, median 11 years), with a strong male preponderance (4:1). All patients had inflammatory conjunctivitis. One patient had recurrent conjunctival pseudomembrane formation, whereas 2 patients had lid margin and conjunctival ulceration. No cases had corneal involvement and visual outcomes were excellent., Conclusions: MIRM is associated with ocular involvement in almost all cases. Although this is generally mild, conjunctival epithelial defects and pseudomembrane formation can occur. We recommend that pediatric ophthalmologists follow children who are hospitalized with MIRM as closely as they would those diagnosed with other mucocutaneous syndromes, such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

As a widely used cancer drug, carboplatin often results in serious side effects, such as gut toxicity. In this study, we examined the effects of gut microbiota on mice with carboplatin-induced intestinal mucosal damage. Carboplatin resulted in intestinal mucositis, as indicated by weight loss, diarrhoea, and infiltration of inflammatory cells. It markedly increased the expression of inflammatory cytokines/chemokines in intestine. Carboplatin also altered the diversity and composition of the gut microbiota. A significantly higher abundance of Prevotella copri (P. copri) was observed in carboplatin-treated mice. Moreover, the content of P. copri was positively correlated with the severity of intestinal mucositis. Pretreatment with metronidazole reduced the content of P. copri and relieved the intestinal mucosal injury and inflammation that was induced by carboplatin. Further study revealed that supplementation with P. copri in carboplatin-treated mice resulted in more severe tissue damage, lower tight junction protein expression and higher cytokine expression, and it enhanced both local and systemic immune responses. These data demonstrated that P. copri was involved in the pathological process of carboplatin-induced intestinal mucositis, suggesting a potential attenuation of carboplatin-induced intestinal mucositis by targeting P. copri.

In the era of modern technology is becoming increasingly popular implantation. This method is one of the leading methods in prosthetics of dental patients. Implantation solves a number of problems both aesthetic and functional. However, the percentage of complications, such as peri-implantitis and mucositis, leading to a violation of the chewing function of the dentition, is steadily increasing. To date, the etiology and pathogenesis of post-implantation complications have not been definitively clarified. One of the leading predictors is psychoemotional stress. On the basis of the literature analysis method to study stress, its impact on the development of periimplantitis, is laser Doppler flowmetry, allows you to quickly assess the state of microcirculation of the oral cavity at the stage of diagnosis, prior to the commencement of pharmacotherapy and in the dynamics of treatment and to adjust treatment regimen to prevent postoperative complications. The obtained LDF-grams allow to reflect the state of the regulatory systems of the body, and therefore it is possible to use LDF for the diagnosis of psychological stress.

Mucositis is an inflammatory condition of the gut, caused by an adverse effect of chemotherapy drugs, such as 5-fluorouracil (5-FU). In an attempt to develop alternative treatments for the disease, several research groups have proposed the use of probiotics, in particular, Lactic Acid Bacteria (LAB). In this context, the use of recombinant LAB, for delivering anti-inflammatory compounds has also been explored. In previous work, we demonstrated that either Lactococcus lactis NZ9000 or a recombinant strain expressing an antimicrobial peptide involved in human gut homeostasis, the Pancreatitis-associated Protein (PAP), could ameliorate 5-FU-induced mucositis in mice. However, the impact of these strains on the gut microbiota still needs to be elucidated. Therefore, in the present study, we aimed to characterize the effects of both Lactococci strains in the gut microbiome of mice through a 16 S rRNA gene sequencing metagenomic approach. Our data show 5-FU caused a significant decrease in protective bacteria and increase of several bacteria associated with pro-inflammatory traits. The Lactococci strains were shown to reduce several potential opportunistic microbes, while PAP delivery was able to suppress the growth of Enterobacteriaceae during inflammation. We conclude the strain secreting antimicrobial PAP was more effective in the control of 5-FU-dysbiosis.

Objectives: This study investigated the presence of Streptococci, Staphylococci, aerobic gram negative bacteria (AGNB), Candida and bacterial endotoxins in the oral cavities of patients receiving chemo- and/or radiotherapy for cancer., Methods: Samples of oral cavity rinse were collected from 100 patients on cancer treatment and 70 healthy individuals. Demographic and clinical data were recorded. Samples were cultured onto various agar plates for qualitative and quantitative analysis and tested for the presence of endotoxin. Results were analysed using the Mann-Whitney and chi-square tests., Results: In cancer patients, S. aureus counts were high and 66.7% of patients on chemo- and radiotherapy carried these bacteria (p=<0.05). The Candida carrier rate was significantly (p < 0.01) high in cancer patients (54%). No significant difference was found in the carrier rate of Streptococci and AGNB between the healthy and cancer group as well as between the cancer patients with chemo and radio- and chemotherapy alone. No significant difference was found in the level of endotoxin between the cancer patients and healthy individuals, and cancer patients with and without AGNB., Conclusions: No differences in the prevalence of bacteria and bacterial endotoxins were found between the cancer patients and healthy individuals. Oral cavity endotoxins did not correlate with the carriage of AGNB. However, due to the high prevalence in cancer patients, the role of Candida species and S. aureus in the pathology may not be excluded., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases., Objective: To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model., Methods: Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated., Results: Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines., Conclusion: This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Mycoplasma pneumoniae infection has been documented in erythema multiforme (EM) and Stevens-Johnson syndrome-toxic epidermal necrosis (SJS-TEN). Clinical aspects of M pneumoniae-related EM have been poorly described in the literature., Objective: To highlight differences between M pneumoniae EM and non-M pneumoniae EM., Methods: This single-center, retrospective cohort study included all patients admitted to our dermatology department for EM during 2000-2015. We compared epidemiologic, clinical, and histologic data and follow-up for M pneumoniae EM and non-M pneumoniae EM cases., Results: Thirty-three patients with M pneumoniae EM were compared with 100 patients with non-M pneumoniae EM. Disease onset in winter was more frequent with M pneumoniae EM (P = .003). Acrally distributed lesions (32% vs 88%, P < .0001) and typical targets (45% vs 74%, P = .01) were less common in M pneumoniae EM than non-M pneumoniae EM. Multiple (≥2) mucousal membrane involvement was more frequent in M pneumoniae EM than non-M pneumoniae EM (97% vs 60%; P < .0001), as were mucosal and respiratory tract sequelae (P < .05). The mean hospital stay was longer with M pneumoniae EM patients: 9.5 days versus 5.1 days (P = .0002). A TEN-like pattern was observed in all 14 (100%) M pneumoniae EM skin biopsies versus 10 of 27 (48%) non-M pneumoniae EM biopsies (P < .001)., Limitations: The retrospective design., Conclusion: M pneumoniae EM has a distinctive presentation compared with non-M pneumoniae EM, with more diffuse and atypical targets, more mucositis and respiratory tract sequelae. Histologic data show a TEN-like pattern in all M pneumoniae EM skin samples., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

This case report describes a father and son with recurrent Mycoplasma-induced rash and mucositis (MIRM). A father with a remote history of a similar rash in childhood presented to the hospital with a severe rash with mucosal involvement, and elevated Mycoplasma pneumoniae immunoglobulin M titers, consistent with MIRM. Four years later, a similar rash developed in his son with a positive M. pneumoniae polymerase chain reaction assay, which was consistent with MIRM. His course was complicated by recurrence of disease shortly after discharge from the hospital. To our knowledge, this case report is the first to describe recurrent MIRM affecting individuals within the same family.

Objectives: The objective of this study is to evaluate the effects of treatment modalities on titanium surface characteristics and surrounding tissues., Materials and Methods: Eighteen participants each had four titanium healing caps (HC) attached to four newly inserted implants. After healing, each HC was randomly assigned to either (1) titanium curettes (TC), (2) stainless steel ultrasonic tip (PS), (3) erythritol air-polishing powder (EP), or (4) only rubber cup polishing (CON). Probing depths (PD), bleeding on probing (BOP), matrix metalloproteinase 8 (MMP-8), and periopathogens were recorded before and 3 months following instrumentation. After final assessments, HCs were removed, cleaned, and subjected to (a) bacterial colonization (Streptococcus gordonii, 24 h; mixed culture, 24 h) and (b) gingival fibroblasts (5 days). HC surfaces were analyzed with a scanning electron microscope (SEM)., Results: No significant differences between the groups were evident before or after instrumentation for PD and BOP (except TC showed a significant decrease in PD; p = 0.049). MMP-8 levels and bacterial loads were always very low. MMP-8 decreased further after instrumentation, while bacteria levels showed no change. No significant differences (p > 0.05) were evident in bacterial colonization or fibroblast attachment. A comparison of the overall mean SEM surface roughness scores showed a significant difference between all groups (p < 0.0001) with the lowest roughness after EP., Conclusions: All treatments performed yielded comparable outcomes and may be implemented safely., Clinical Relevance: Clinicians may fear implant surface damage, but all instrumentation types are safe and non-damaging. They can be implemented as needed upon considering the presence of staining and soft and hard deposits.

Oral mucoceles are lesions arising mainly from the minor salivary glands and are thought to occur after excretory duct trauma. We report a case of multiple superficial oral mucoceles on a child's labial mucosa after Mycoplasma pneumoniae mucositis. Mucoceles can mimic persistent or recurrent stomatitis and lead to potential errors in management., (© 2018 Wiley Periodicals, Inc.)

Background and Objective: Oral probiotics appear to improve the treatment of periodontal diseases but there is limited evidence on their efficacy in the treatment of peri-implant diseases. The objective of the present study was to evaluate, clinically and microbiologically, the effect of the oral probiotic, Lactobacillus reuteri Prodentis, as adjuvant to non-surgical mechanical therapy in implants with mucositis or peri-implantitis, placed in patients with a history of periodontal disease., Material and Methods: A randomized, controlled, parallel-design, triple-blind prospective clinical study was designed. Patients included in the study were partially edentulous and had implants with mucositis or peri-implantitis. Implants with radiographic bone loss of ≥5 mm and/or ≥50% of the implant length were excluded, and only one implant per patient was included. After non-surgical mechanical therapy, subjects were randomly assigned to take either 1 probiotic lozenge or 1 placebo lozenge every day for 30 days. Clinical measurements were taken in the whole mouth (general plaque index and general bleeding on probing) and at the implant site (probing pocket depth, plaque index and bleeding on probing) at baseline and 30 and 90 days Microbiological examination (to identify Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Peptostreptococcus micros, Fusobacterium nucleatum, Campylobacter rectus and Eikenella corrodens) was performed at the same study time points that clinical measurements were made., Results: A total of 44 patients - 22 with mucositis and 22 with peri-implantitis - randomly received treatment with either probiotic or placebo. The probiotic L. reuteri, together with mechanical therapy, produced an additional improvement over treatment with mechanical therapy alone, both in the general clinical parameters of patients with mucositis (bleeding on probing) and at the level of implants with mucositis (probing pocket depth) or peri-implantitis (bleeding on probing and probing pocket depth). However, L. reuteri had a very limited effect on the peri-implant microbiota because the only parameter in which a significant decrease was found was the bacterial load of P. gingivalis in implants with mucositis (P = .031)., Conclusion: The administration of a daily lozenge of L. reuteri for 30 days, together with mechanical debridement of the whole mouth, improved the clinical parameters of implants with mucositis or peri-implantitis over a period of at least 90 days, but the microbiological effect was much more limited. Probiotics provide an alternative therapeutic approach to consider in the prevention and treatment of peri-implant diseases, but further long-term prospective studies with standardized variables are needed., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Porphyromonas gingivalis and Tannerella forsythia secrete proteases, gingipains and KLIKK-proteases. In addition, T. forsythia produces a serpin (miropin) with broad inhibitory spectrum. The aim of this pilot study was to determine the level of expression of miropin and individual proteases in vivo in periodontal and peri-implant health and disease conditions. Biofilm and gingival crevicular fluid (GCF)/ peri-implant sulcular fluid (PISF) samples were taken from healthy tooth and implant sites (n = 10), gingivitis and mucositis sites (n = 12), and periodontitis and peri-implantitis sites (n = 10). Concentration of interleukin-8 (IL-8), IL-1β and IL-10 in GCF was determined by enzyme-linked immunosorbent assay. Loads of P. gingivalis and T. forsythia and the presence of proteases and miropin genes were assessed in biofilm by quantitative PCR, whereas gene expression was estimated by quantitative RT-PCR. The presence of P. gingivalis and T. forsythia, as well as the level of IL-8 and IL-1β, were associated with disease severity in the periodontal and peri-implant tissues. In biofilm samples harboring T. forsythia, genes encoding proteases were found to be present at 72.4% for karilysin and 100% for other KLIKK-protease genes and miropin. At the same time, detectable mRNA expression of individual genes ranged from 20.7% to 58.6% of samples (for forsylisin and miropsin-1, respectively). In comparison with the T. forsythia proteases, miropin and the gingipains were highly expressed. The level of expression of gingipains was associated with those of miropin and certain T. forsythia proteases around teeth but not implants. Cumulatively, KLIKK-proteases and especially miropin, might play a role in pathogenesis of both periodontal and peri-implant diseases., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)