RESUMO
This network meta-analysis aims to compare the clinical efficacy of seven non-surgical therapies for peri-implant disease, including laser treatment, photobiomodulation therapy (PBMT), photodynamic therapy (PDT), systemic antibiotics (SA), probiotics, local antimicrobials (LA), and air-powder polishing (APP) combined with mechanical debridement (MD). We conducted searches in four electronic databases, namely PubMed, Embase, Web of Science, and The Cochrane Library, to identify randomized controlled trials of non-surgical treatments combined with MD for individuals (aged at least 18 years) diagnosed with peri-implantitis or peri-implant mucositis with a minimum of 3 months follow-up. The outcomes of the study were the reduction in pocket probing depth (PPD) and bleeding on probing (BoP), plaque index (PLI), clinical attachment level (CAL), and marginal bone loss (MBL). We employed a frequency random effects network meta-analysis model to combine the effect sizes of the trials using standardized mean difference (SMD) and 95% confidence intervals (CIs). Network meta-analyses include network plots, paired comparison forest plots, league tables, funnel plots, surface under the cumulative ranking area (SUCRA) plots, and sensitivity analysis plots. The results showed that, for peri-implantitis, PBMT +MD demonstrated the highest effect in improving PPD (SUCRA = 75.3%), SA +MD showed the highest effect in improving CAL (SUCRA = 87.4%, SMD = 2.20, and 95% CI: 0.38 to 4.02) and MBL (SUCRA = 99.9%, SMD = 3.92, and 95% CI. 2.90 to 4.93), compared to MD alone. For peri-implant mucositis, probiotics +MD demonstrated the highest effect in improving PPD (SUCRA = 100%) and PLI (SUCRA = 83.2%), SA +MD showed the highest effect in improving BoP (SUCRA = 88.1%, SMD = 0.77, and 95% CI: 0.27 to 1.28), compared to MD alone. Despite the ranking established by our study in the treatment of peri-implant disease, decisions should still be made with reference to the latest treatment guidelines. There is still a need for more high-quality studies to provide conclusive evidence and especially a need for studies regarding direct comparisons between multiple treatment options.
Assuntos
Desbridamento , Peri-Implantite , Humanos , Peri-Implantite/terapia , Desbridamento/métodos , Metanálise em Rede , Resultado do Tratamento , Fotoquimioterapia/métodos , Probióticos/uso terapêutico , Antibacterianos/uso terapêutico , Implantes Dentários/efeitos adversos , Estomatite/terapia , Estomatite/radioterapia , Estomatite/etiologia , Mucosite/terapia , Terapia a Laser/métodosRESUMO
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.
Assuntos
Febre , Mucosite , Neutropenia , Humanos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Fatores de Risco , Mucosite/etiologia , Neutropenia/etiologia , Neutropenia/complicações , Idoso , Febre/etiologia , Adulto , Países Baixos , Índice de Gravidade de Doença , Candidemia/etiologia , Candidemia/epidemiologia , Neoplasias Hematológicas/complicaçõesRESUMO
Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal rather than a monoclonal plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. In this work, we provide a review and update on PCM, which often represents a clinical conundrum.
Assuntos
Mucosite , Plasmócitos , Humanos , Mucosite/terapia , Mucosite/etiologia , Mucosite/diagnóstico , Plasmócitos/patologiaRESUMO
BACKGROUND: Today, a number of methods and ways of prevention and treatment of radiation- -induced mucositis of the oral cavity and oropharynx have been developed, but the represented approaches are still not effective enough. Therefore, to increase the effectiveness of the prevention and treatment of radiation-induced mucositis, it is necessary to approach this problem comprehensively and individually, and to evaluate the factors affecting the development of mucositis. MATERIALS AND METHODS: In this single-center prospective controlled non-randomized clinical trial, the results of clinical observation of the development of complications of radiation and chemoradiation therapy in 105 patients with a newly diagnosed squamous cell cancer of the oral cavity and oropharynx were analyzed. Factors affecting the risk of the development of grade III radiation-induced mucositis including the age, gender of the patients, their general condition before the treatment according to World Health Organisation scales, type of the treatment and its doses, additional use of immunotherapy with alpha/beta defensins, characteristic signs of the tumor process and all indices of the immune status of the patients before the treatment have been analyzed. RESULTS: The method of construction and analysis of one-factor logistic regression models, where 24 indices were analyzed as factorial features, showed that the reduction of the risk of the development of grade III radiation-induced mucositis is predicted by several factors: immunotherapy, gender, serum concentrations of IgG and IgA. A decrease (P < 0.001) in the risk of the development of grade III radiation-induced mucositis was revealed if immunotherapy with alpha/beta defensins (with a total dose of 40â mg) was included into the treatment scheme (relative odds (RO) 0.05; 95% reference interval (RI) 0.02-0.18), in comparison with patients of the groups where it was not present or this immune agent was used in a total dose of 60â mg (P = 0.001, RO 0.06; 95% RI 0.01-0.30). The next factorial sign was gender, namely the risk of the development of grade III radiation-induced mucositis was lower for men (P = 0.003; RO 0.15; 95% RI 0.04-0.53) compared to women. An increase (P = 0.024) in the risk of the development of grade III radiation-induced mucositis with an increase in the initial level of IgG serum concentration was revealed, (RO 1.08; 95% RI 1.01-1.16) for each 1â mg/mL, as well as an increase (P = 0.044) in the possibility of the appearance of grade III radiation-induced mucositis with an increase in the serum concentration of IgA (RO 1.23; 95% RI 1.01-1.50) for every 1â mg/mL also before the beginning of the treatment. Multifactorial analysis has also confirmed that the risk of the development of grade III radiation-induced mucositis increases (P = 0.008) with a high serum IgG concentration before the treatment or with an increase in this index during therapy (RO 1.13; 95% RI 1.03-1.09) for every 1â mg/mL (when standardized by other risk factors). It was determined that when standardizing according to other factors (gender, IgG level), the risk of the development of grade III radiation-induced mucositis in the use of the immune agent alpha/beta defensins in a total dose of 40â mg per course decreases (P < 0.001; RO 0.08; 95% RI 0.02-0.27) compared to patients with oral cavity and oropharynx cancer who were not treated with immunotherapy. The risk of the development of grade III radiation-induced mucositis also decreases (P = 0.001) in the use of immunotherapy in a higher dose, i.e. 60â mg per course (RO 0.03; 95% RI 0.004-0.24 compared to patients whose treatment did not include immunotherapy (when standardized by other factors). CONCLUSION: As a result of this controlled clinical study, some factors were determined in addition to the radiation as those affecting the risk of the development of grade III radiation-induced mucositis in patients with oral cavity and oropharynx cancer during special treatment. These factors comprise the inclusion of immunotherapy with alpha/beta defensins into the specific treatment; gender, and baseline levels of serum IgG and IgA concentrations suggest a pattern in which the higher the serum IgG and IgA concentrations are before the start of the treatment, the greater is the likelihood of severe radiation-induced mucositis degree during special therapy. The results of the study of humoral state of the immune system in patients with oral cavity and oropharynx cancer before the beginning of chemoradiation therapy can be used as prognostic risk factors for the development of severe gamma-irradiation-induced mucositis of the oropharyngeal area, as well as an indication for the use of immunotherapeutic agents (in particular, alpha/beta defensins) that are able to polarize the immune response towards type 1 T-helpers through their immunomodulatory action.
Assuntos
Quimiorradioterapia , Neoplasias Bucais , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/terapia , Masculino , Feminino , Quimiorradioterapia/efeitos adversos , Neoplasias Bucais/radioterapia , Neoplasias Bucais/tratamento farmacológico , Fatores de Risco , Lesões por Radiação/etiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Mucosite/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Idoso , Estomatite/etiologiaRESUMO
Chemotherapy-induced mucositis (CIM) is the typical side effect of chemotherapy. This study investigates the potential of alginate oligosaccharide (AOS) in ameliorating CIM induced by 5-fluorouracil (5-FU) in a murine model and its underlying mechanisms. AOS effectively mitigated body weight loss and histopathological damage, modulated inflammatory cytokines and attenuated the oxidative stress. AOS restored intestinal barrier integrity through enhancing expression of tight junction proteins via MLCK signaling pathway. AOS alleviated intestinal mucosal damage by inhibiting TLR4/MyD88/NF-κB signaling pathway, downregulating the pro-apoptotic protein Bax and upregulating the anti-apoptotic protein Bcl-2. Moreover, AOS significantly enriched intestinal Akkermansiaceae and increased the production of short-chain fatty acids (SCFAs), most notably butyrate and isovalerate. Pre-treatment with butyrate and isovalerate also alleviated 5-FU-induced CIM. In conclusion, AOS effectively mitigated CIM through strenghthening intestinal barrier, attenuating inflammation, and modulating gut microbiota and intestianl levels of butyrate and isovalerate. These finding indicate that AOS could be potentially utilized as a supplemental strategy for prevention or mitigation of CIM.
Assuntos
Alginatos , Butiratos , Fluoruracila , Mucosa Intestinal , Mucosite , Oligossacarídeos , Fluoruracila/efeitos adversos , Animais , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/metabolismo , Mucosite/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Oligossacarídeos/farmacologia , Oligossacarídeos/química , Butiratos/farmacologia , Butiratos/metabolismo , Alginatos/farmacologia , Alginatos/química , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Citocinas/metabolismoRESUMO
High-dose methotrexate (HD-MTX) is used in the treatment of children with central nervous system (CNS) tumors; however, toxicity information is limited. We characterized toxicities following 102 administrations of HD-MTX (4.6-13.5 g/m2) infused over 4 or 24 h in 38 children with a CNS tumor before 6 years of age (2010-2020). Delayed clearance of methotrexate occurred following 24% of infusions. Common Terminology Criteria for Adverse Events v5 grade 2-3 mucositis was observed in 47% of individuals, Grade 4 neutropenia in 76%, and grade 3-4 thrombocytopenia in 58%. No neurotoxicity was observed. HD-MTX can be safely used with supportive care and monitoring.
Assuntos
Antimetabólitos Antineoplásicos , Neoplasias do Sistema Nervoso Central , Metotrexato , Humanos , Metotrexato/efeitos adversos , Metotrexato/administração & dosagem , Feminino , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Masculino , Pré-Escolar , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Lactente , Criança , Seguimentos , Estudos Retrospectivos , Prognóstico , Mucosite/induzido quimicamente , Neutropenia/induzido quimicamenteRESUMO
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.
Assuntos
Alimentos Fermentados , Peri-Implantite , Probióticos , Humanos , Probióticos/uso terapêutico , Estudos Transversais , Peri-Implantite/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Implantes Dentários/efeitos adversos , Mucosite/prevenção & controle , Inquéritos e Questionários , Estomatite/prevenção & controle , Estomatite/etiologiaRESUMO
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.
Assuntos
Antineoplásicos , Microbioma Gastrointestinal , Mucosite , Humanos , Microbioma Gastrointestinal/fisiologia , Antineoplásicos/efeitos adversos , Mucosite/microbiologia , Mucosite/etiologia , Neoplasias/complicações , Microbiota , Estomatite/microbiologia , Estomatite/etiologia , Progressão da DoençaRESUMO
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.
Assuntos
Mucosa Bucal , Humanos , Mucosa Bucal/efeitos da radiação , Raios X/efeitos adversos , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Masculino , Mucosite/etiologia , Mucosite/patologia , Feminino , Relação Dose-Resposta à Radiação , Estomatite/etiologia , Estomatite/patologia , Adulto , Pessoa de Meia-IdadeRESUMO
Chemotherapy has allowed an increase in cancer survivorship, but it causes important adverse effects. Mucositis affecting the gastrointestinal tract is one of the main problems acutely caused by many antineoplastic drugs, such as 5-fluorouracil or methotrexate. Mucositis may cause pain, diarrhea, anorexia, weight loss, systemic infections and even death. This narrative review focuses on intestinal mucositis and the role that some nutraceuticals, namely vitamins (both lipid- and water-soluble) as well as fatty acids (FAs) and lipid-based products, can have in it. In preclinical (cell cultures, animal models) and/or human studies, vitamins A, D, E, B2, B9 and C, omega-3 long-chain FAs (eicosapentaenoic, docosahexaenoic, conjugated linoleic acid), short-chain FAs (mainly butyrate), medium-chain FAs (capric acid), and different lipid-based products (emu oil, extra-virgin olive oil, lipid replacement therapy), enriched in beneficial FAs and natural antioxidants, were shown to exert beneficial effects (both preventative and palliative) against chemotherapy-induced intestinal mucositis. Although the exact mechanisms of action involved in these effects are not yet well known, our review highlights the interest of investigating on diet and nutrition to implement scientifically robust strategies to improve protection of cancer patients against chemotherapy-induced adverse effects.
Assuntos
Antineoplásicos , Ácidos Graxos , Mucosite , Vitaminas , Humanos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Ácidos Graxos/metabolismo , Vitaminas/uso terapêutico , Vitaminas/farmacologia , Suplementos NutricionaisRESUMO
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.
Assuntos
Bactérias , Implantes Dentários , Disbiose , Microbiota , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Implantes Dentários/microbiologia , Implantes Dentários/efeitos adversos , Adulto , Disbiose/microbiologia , Índice de Gravidade de Doença , Idoso , Gengivite/microbiologia , Peri-Implantite/microbiologia , Mucosite/microbiologia , Estomatite/microbiologia , Estomatite/etiologia , Metagenoma , Biofilmes/crescimento & desenvolvimentoRESUMO
PURPOSE: This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases. METHODS: A cohort of 29 patients with a total of 76 implants was included in this study and subsequently divided into three groups based on peri-implant clinical parameters and radiographic examination: healthy (peri-implant health) (n = 29), mucositis (n = 22), and peri-implantitis (n = 25) groups. The levels of ET-1 (ρg/site) and interleukin (IL)-1ß (ρg/site) in peri-implant sulcus fluid (PISF) samples were determined using enzyme immunoassay. Statistical analyses were conducted using Kruskal-Wallis and Steel-Dwass tests. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of the biomarkers. RESULTS: ET-1 levels were significantly elevated in the peri-implantitis group compared to those in the healthy group, and were highest in the peri-implant mucositis group. Additionally, IL-1ß levels were significantly higher in the peri-implantitis group than those in the healthy group. ROC curve analysis indicated that ET-1 exhibited superior area under the curve values, sensitivity, and specificity compared to those of IL-1ß. CONCLUSIONS: Our findings suggest that the presence of ET-1 in PISF plays a role in peri-implant diseases. Its significantly increased expression in peri-implant mucositis indicates its potential for enabling earlier and more accurate assessments of peri-implant inflammation when combined with conventional examination methods.
Assuntos
Biomarcadores , Endotelina-1 , Interleucina-1beta , Peri-Implantite , Humanos , Endotelina-1/metabolismo , Endotelina-1/análise , Peri-Implantite/diagnóstico , Peri-Implantite/metabolismo , Estudos Transversais , Masculino , Feminino , Biomarcadores/metabolismo , Biomarcadores/análise , Pessoa de Meia-Idade , Interleucina-1beta/metabolismo , Interleucina-1beta/análise , Implantes Dentários/efeitos adversos , Adulto , Mucosite/diagnóstico , Mucosite/metabolismo , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/metabolismo , Idoso , Curva ROCRESUMO
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.
Assuntos
COVID-19 , Diarreia , Microbioma Gastrointestinal , Neoplasias , Probióticos , Qualidade de Vida , Humanos , Probióticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias/tratamento farmacológico , Microbioma Gastrointestinal/fisiologia , Idoso , Diarreia/microbiologia , Estudos de Coortes , Adulto , Fezes/microbiologia , Mucosite , Antineoplásicos/efeitos adversosRESUMO
Chemotherapy is a common and effective treatment for cancer, but these drugs are also associated with significant side effects affecting patients' well-being. One such debilitating side effect is mucositis, characterized by inflammation, ulcerations, and altered physiological functions of the gastrointestinal (GI) tract's mucosal lining. Understanding the mechanisms of chemotherapy-induced intestinal mucositis (CIM) is crucial for developing effective preventive measures and supportive care. Chemotherapeutics not only target cancer cells but also rapidly dividing cells in the GI tract. These drugs disrupt endoplasmic reticulum (ER) homeostasis, leading to ER-stress and activation of the unfolded protein response (UPR) in various intestinal epithelial cell types. The UPR triggers signaling pathways that exacerbate tissue inflammation and damage, influence the differentiation and fate of intestinal epithelial cells, and compromise the integrity of the intestinal mucosal barrier. These factors contribute significantly to mucositis development and progression. In this review, we aim to give an in-depth overview of the role of ER-stress in mucositis and its impact on GI function. This will provide valuable insights into the underlying mechanisms and highlighting potential therapeutic interventions that could improve treatment-outcomes and the quality of life of cancer patients.
Assuntos
Antineoplásicos , Estresse do Retículo Endoplasmático , Mucosite , Humanos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Mucosite/induzido quimicamente , Mucosite/metabolismo , Antineoplásicos/efeitos adversos , Animais , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologiaRESUMO
BACKGROUND: The aim of this study was to investigate the association between peri-implant diseases and systemic inflammation assessed by serum C-reactive protein (CRP) levels in a sample of patients with hypertension. METHODS: A total of 151 participants with hypertension were included in a cross-sectional study. The population was divided into six groups according to their peri-implant and periodontal status (healthy controls, mucositis, peri-implantitis, periodontitis, periodontitis and mucositis, periodontitis, and peri-implantitis). Linear, logistic regression, and correlation analyses were performed. RESULTS: CRP levels were statistically significantly higher in participants with periodontitis alone (median 3.2 mg/L, interquartile range [IQR] 1.8, p = 0.012), combined with mucositis (3.10 mg/L, IQR 2.35, p < 0.001) or peri-implantitis (2.7 mg/L, IQR 2.53, p = 0.002) when compared to the healthy controls (1 mg/L, IQR 1.2). This association was independent of age, sex, smoking status, and adiposity differences. Participants with periodontitis with and without peri-implant diseases had the greatest odds of exhibiting CRP > 3 mg/L (odds ratio = 7.3, 95% confidence interval 1.6-33.9). CONCLUSIONS: Peri-implant diseases are associated with systemic inflammation, but the nature of the association should be further investigated.
Assuntos
Proteína C-Reativa , Hipertensão , Inflamação , Mucosite , Peri-Implantite , Periodontite , Estomatite , Humanos , Estudos Transversais , Feminino , Masculino , Proteína C-Reativa/análise , Hipertensão/complicações , Pessoa de Meia-Idade , Peri-Implantite/sangue , Periodontite/sangue , Periodontite/complicações , Idoso , Inflamação/sangue , Estomatite/sangue , Estomatite/etiologia , Mucosite/etiologia , Mucosite/sangue , Fumar , Adulto , Implantes Dentários , Fatores Sexuais , Fatores EtáriosRESUMO
Gastrointestinal mucositis (GIM) continues to be a significant issue in the management of abdominal cancer radiation treatments and chemotherapy, causing significant patient discomfort and therapy interruption or even cessation. This review will first focus on radiotherapy induced GIM, providing an understanding of its clinical landscape. Subsequently, the aetiology of GIM will be reviewed, highlighting diverse contributing factors. The cellular and tissue damage and associated molecular responses in GIM will be summarised in the context of the underlying complex biological processes. Finally, available drugs and pharmaceutical therapies will be evaluated, underscoring their insufficiency, and highlighting the need for further research and innovation. This review will emphasize the urgent need for improved pharmacologic therapeutics for GIM, which is a key research priority in oncology.
Assuntos
Mucosite , Lesões por Radiação , Humanos , Mucosite/tratamento farmacológico , Mucosite/etiologia , Lesões por Radiação/tratamento farmacológico , Animais , Radioterapia/efeitos adversos , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/etiologiaRESUMO
Methotrexate (MTX)-induced gastrointestinal mucositis is a common adverse effect characterized by redox imbalance and overproduction of inflammatory mediators that perturb intestinal integrity. Currently, there is no definitive treatment for this condition and its prevention is still far beyond comprehension. Because of its pleiotropic pharmacological actions, we aimed to explore the potential mechanisms through which cilostazol (CILO) can protect against MTX-induced intestinal mucositis. Wistar rats were allocated into 4 groups, control, CILO (100 mg/kg, p.o for 14 days), MTX (7.5 mg/kg for 4 successive days), and CILO + MTX. The improving effect of CILO on the morphological structure was confirmed by an upturn in the histopathological and transition electron microscope examinations evidenced by the increased jejunal villus height/width and the crypt depth besides the maintenance of tight junctions. These findings were verified biochemically; on the molecular level, CILO reduced the MTX-induced lipid peroxidation, cleaved caspase-3, p53, and the inflammatory parameters (TLR-2, NF-κB, IL-23, TNF-α, IL-1ß), while increasing the anti-inflammatory marker IL-10 and the antioxidant enzyme SOD. Moreover, CILO decreased the injurious axis AKT/GSK-3ß/cyclin-D1, and CD44+, but increased the immunoexpression of the cell proliferating marker PCNA. CILO also upheld the intestinal barrier by enhancing the tight junction molecules (ZO-1, claudin-4) and the E-cadherin/ß-catenin complex while abating the mesenchymal marker vimentin. In conclusion, CILO protected gut integrity by reducing the epithelial-mesenchymal transition process, the MTX-induced oxidative, apoptotic, and inflammatory mediators, and turning off the CD44/AKT/GSK-3ß/cyclin D1 trajectory and intensifying the expression of PCNA.
Assuntos
Ciclina D1 , Glicogênio Sintase Quinase 3 beta , Metotrexato , Mucosite , NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Ratos Wistar , Receptor 2 Toll-Like , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , NF-kappa B/metabolismo , Metotrexato/toxicidade , Metotrexato/farmacologia , Ratos , Receptor 2 Toll-Like/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Mucosite/induzido quimicamente , Mucosite/patologia , Mucosite/metabolismo , Masculino , Ciclina D1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Modelos Animais de DoençasRESUMO
Peri-implant diseases are frequent complications that occur around osseointegrated endosseous implants and are the result of an imbalance between the bacterial challenge and host response. Peri-implant diseases may affect the peri-implant mucosa only (peri-implant mucositis) or also involve the supporting bone (peri-implantitis). Early detection of peri-implant diseases and timely treatment is important for the success of dental implant treatment. Peri-implant probing is essential to assess the peri-implant health status and should be done at each recall visit. Dental practitioners should be familiar with the clinical and radiological features of both conditions in order to make an accurate diagnosis and determine the appropriate treatment required. This article aims to provide clinicians with an understanding of the key differences between peri-implant health, peri-implant mucositis and peri-implantitis.