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Life Sciences Nov 2023A diverse and stable microbiota promotes a healthy state, nevertheless, an imbalance in gut or oral bacterial composition, called dysbiosis, can cause gastrointestinal... (Review)
Review
A diverse and stable microbiota promotes a healthy state, nevertheless, an imbalance in gut or oral bacterial composition, called dysbiosis, can cause gastrointestinal disorders, systemic inflammatory states and oxidative stress, among others. Recently, gut and oral dysbiosis has been linked to Alzheimer's disease (AD), which is considered the most common form of dementia and a public health priority due to its high prevalence and incidence. The aim of this review is to highlight the implications of gut and oral microbiota in the neuroinflammation characteristic of AD pathology and the subsequent cognitive impairment. It is a systematic review of the current literature obtained by searching the PubMed, Web of Science and Scopus databases. The characteristic intestinal dysbiosis in AD patients leads to increased permeability of the intestinal barrier and activates immune cells in the central nervous system due to translocation of microbiota-derived metabolites and/or bacteria into the circulation leading to increased neuroinflammation and neuronal loss, thus generating the cognitive impairment characteristic of AD. The presence in the central nervous system of Porphyromonas gingivalis can cause an increased neuroinflammation and beta-amyloid peptide accumulation.
Topics: Humans; Alzheimer Disease; Gastrointestinal Microbiome; Neuroinflammatory Diseases; Dysbiosis; Microbiota; Inflammation; Bacteria; Brain
PubMed: 37793482
DOI: 10.1016/j.lfs.2023.122132 -
Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025 -
BJOG : An International Journal of... Apr 2023High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.
OBJECTIVES
To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.
SEARCH STRATEGY
MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.
SELECTION CRITERIA
Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%.
CONCLUSIONS
High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Hydatidiform Mole; Retrospective Studies
PubMed: 36648416
DOI: 10.1111/1471-0528.17374 -
Clinical Oral Investigations Aug 2023This review aimed at evaluating the possible benefits that caloric restriction (CR) may provide to periodontal disease progression and response to treatment. (Review)
Review
OBJECTIVE
This review aimed at evaluating the possible benefits that caloric restriction (CR) may provide to periodontal disease progression and response to treatment.
MATERIAL AND METHODS
Electronic search on Medline, Embase and Cochrane, and manual search were performed to identify pre-clinical and on human studies reporting the consequences of CR on clinical and inflammatory parameters related to periodontitis. Newcastle Ottawa System and SYRCLE scale were used to assess the risk of bias.
RESULTS
Four thousand nine hundred eighty articles were initially screened, and a total of 6 articles were finally included, consisting of 4 animal studies and 2 studies in humans. Due to the limited number of studies and heterogeneity of the data, results were presented in descriptive analyses. All studies showed that, compared to the normal (ad libitum) diet, CR might have the potential to reduce the local and systemic hyper-inflammatory state as well as disease progression in periodontal patients.
CONCLUSIONS
Within the existing limitations, this review highlights that CR showed some improvements in the periodontal condition by reducing the local and systemic inflammation related to the periodontitis and by improving clinical parameters. However, the results should be interpreted with caution since robust research such as randomized clinical trials is still missing.
CLINICAL RELEVANCE
This review shows that some dietary/caloric restrictions approaches may have the potential to improve periodontal conditions and, in addition, highlights a need for human studies with a robust methodology in order to draw stronger evidence-based conclusions.
Topics: Animals; Humans; Periodontal Diseases; Periodontitis; Gingival Diseases; Disease Progression
PubMed: 37199773
DOI: 10.1007/s00784-023-05052-9 -
Current Developments in Nutrition Oct 2023Cannabidiol (CBD) is a non-intoxicating cannabinoid extracted from the cannabis plant that is used for medicinal purposes. Ingestion of CBD is claimed to address several... (Review)
Review
Cannabidiol (CBD) is a non-intoxicating cannabinoid extracted from the cannabis plant that is used for medicinal purposes. Ingestion of CBD is claimed to address several pathologies, including gastrointestinal disorders, although limited evidence has been generated thus far to substantiate many of its health claims. Nevertheless, CBD usage as an over-the-counter treatment for gastrointestinal disorders is likely to expand in response to increasing commercial availability, permissive legal status, and acceptance by consumers. This systematic review critically evaluates the knowledge boundaries of the published research on CBD, intestinal motility, and intestinal motility disorders. Research on CBD and intestinal motility is currently limited but does support the safety and efficacy of CBD for several therapeutic applications, including seizure disorders, inflammatory responses, and upper gastrointestinal dysfunction (i.e., nausea and vomiting). CBD, therefore, may have therapeutic potential for addressing functional gastrointestinal disorders. The results of this review show promising and preclinical data supporting a role of CBD in intestinal motility. This includes improved gastrointestinal-related outcomes in murine models of colitis. These studies, however, vary by dose, delivery method, and CBD-extract composition. Clinical trials have yet to find a conclusive benefit of CBD on intestinal motility disorders, but these trials have been limited in scope. In addition, critical factors such as CBD dosing parameters have not yet been established. Further research will establish the efficacy of CBD in applications to address intestinal motility.
PubMed: 37786751
DOI: 10.1016/j.cdnut.2023.101972 -
Brain, Behavior, & Immunity - Health May 2022Dysregulated immune response arising in the periphery can induce depressive symptoms through neuroimmune interactions. Inflammatory oral pathology can be a potent... (Review)
Review
BACKGROUND
Dysregulated immune response arising in the periphery can induce depressive symptoms through neuroimmune interactions. Inflammatory oral pathology can be a potent inducer of chronic neuroimmune response relevant to depression. We aimed to synthesize available evidence for the association between inflammatory periodontal diseases (IPD) and major depression (MD) in relation to a broad range of biomarkers.
METHODS
Medline, Embase, PsycInfo, Cochrane Library, Web of Science and Scopus databases were searched from inception until January 27, 2022. Search terms included subject headings and synonyms for inflammatory periodontal disease and depression. Studies that reported data on both depression and inflammatory periodontal disease as categories along with measurement of a biomarker were considered. Two reviewers independently selected the articles for inclusion, extracted data and assessed the quality of each study. The protocol for this study was registered with PROSPERO, CRD42021215524.
RESULTS
Twenty-eight studies were included in the final review-eleven cross-sectional studies, seven case-control studies, and six prospective cohort studies conducted in humans; the remaining four were experimental animal studies. Eighteen studies including all animal studies reported a positive association between depression and periodontal disease; one study reported a negative association and another nine studies found no such associations. Twenty studies reported mixed associations between IPD and biomarkers (i.e, salivary, serum, urine or gingival crevicular fluid cortisol, C reactive protein, cytokines, etc.). Biomarkers related to depression were gingival crevicular fluid cortisol, interleukin 6 (IL-6), Il-1β, immunoglobulin G against Bacterioides forsythus; root canal lipopolysaccharides; blood IL-6, IL-1β, cortisol, advanced oxidation protein products, nitric oxide metabolites, lipid hydroperoxides and trapping antioxidant parameter; whereas five studies found no associations between depression and a biomarker. Although animal studies showed interaction of immune, inflammatory and neurotrophic biomarkers in the relationship between depression and periodontal disease, human studies showed mixed findings. In most studies, there were risks of bias due to the sample selection and assessment protocol. Study heterogeneity and limited number of comparable studies reporting on shared biomarkers precluded a meta-analysis.
CONCLUSION
Immune-inflammatory contribution to depression was evident in the context of inflammatory periodontal diseases, but whether biomarkers mediate the associations between IPD and MD needs to be tested through methodologically rigorous studies aiming specifically at this hypothesis.
PubMed: 35330865
DOI: 10.1016/j.bbih.2022.100450 -
European Journal of Epidemiology May 2023To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients... (Meta-Analysis)
Meta-Analysis Review
AIMS
To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations.
METHODS AND RESULTS
We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI ) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01-1.18, I: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04-1.34, I: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11-1.58, I: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10-1.43, I: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13-5.64, I: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (P > 0.05).
CONCLUSION
This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person's lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality.
Topics: Adult; Humans; Lipoprotein(a); Cause of Death; Prospective Studies; Cardiovascular Diseases; Risk Factors
PubMed: 36708412
DOI: 10.1007/s10654-022-00956-4 -
Brain Sciences Mar 2023Although the distinction between vascular parkinsonism (VP) and idiopathic Parkinson's disease (IPD) is widely described, it is not uncommon to find parkinsonisms with... (Review)
Review
BACKGROUND AND AIMS
Although the distinction between vascular parkinsonism (VP) and idiopathic Parkinson's disease (IPD) is widely described, it is not uncommon to find parkinsonisms with overlapping clinical and neuroimaging features even in response to levodopa treatment. In addition, several treatments have been described as possible adjuvants in VP. This study aims to update and analyze the different treatments and their efficacy in VP.
METHODS
A literature search was performed in PubMed, Scopus and Web of Science for studies published in the last 15 years until April 2022. A systematic review was performed. No meta-analysis was performed as no new studies on response to levodopa in VP were found since the last systematic review and meta-analysis in 2017, and insufficient studies on other treatments were located to conduct it in another treatment subgroup.
RESULTS
Databases and other sources yielded 59 publications after eliminating duplicates, and a total of 12 original studies were finally included in the systematic review. The treatments evaluated included levodopa, vitamin D, repetitive transcranial magnetic stimulation (rTMS) and intracerebral transcatheter laser photobiomodulation therapy (PBMT). The response to levodopa was lower in patients with VP with respect to IPD. Despite this, there has been described a subgroup of patients with good response, it being possible to identify them by means of neuroimaging techniques and the olfactory identification test. Other therapies showed encouraging results in studies with some risk of bias.
CONCLUSIONS
The response of VP to different therapeutic strategies is modest. However, there is evidence that a subgroup of patients can be identified as more responsive to L-dopa based on clinical and neuroimaging criteria. This subgroup should be treated with L-dopa at appropriate doses. New therapies such as vitamin D, rTMS and PBMT warrant further studies to demonstrate their efficacy.
PubMed: 36979299
DOI: 10.3390/brainsci13030489 -
Frontiers in Immunology 2019Despite the large number of performed studies, the etiology and pathogenesis of sarcoidosis still remain unknown. Most researchers allude to the possible autoimmune or...
Despite the large number of performed studies, the etiology and pathogenesis of sarcoidosis still remain unknown. Most researchers allude to the possible autoimmune or immune-mediated genesis of the disease. This review attempts an integral analysis of currently available information suggesting an autoimmune genesis of sarcoidosis and is divided into four categories: the evaluation of clinical signs described both in patients with sarcoidosis and "classic" autoimmune diseases, the role of triggering factors in the development of sarcoidosis, the presence of immunogenic susceptibility in the development of the disease, and the analysis of cellular and humoral immune responses in sarcoidosis. Studying the etiology and pathogenesis of sarcoidosis will improve diagnostic procedures as well as the prognosis and patients' quality of life.
Topics: Animals; Autoimmune Diseases; Humans; Immunity, Cellular; Immunity, Humoral; Sarcoidosis
PubMed: 31969879
DOI: 10.3389/fimmu.2019.02933 -
BMC Oral Health Jun 2023Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases.
METHODS
The focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained.
RESULTS
Twenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1β, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls.
CONCLUSIONS
The results showed that the levels of IL-1β, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.
Topics: Humans; Cytokines; Peri-Implantitis; Dental Implants; Interleukin-6; Osteogenesis; Gingival Crevicular Fluid
PubMed: 37355561
DOI: 10.1186/s12903-023-03072-1