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Journal of Leukocyte Biology May 2022Inflammation is a key driver of common noncommunicable diseases. Among common triggers of inflammation, chronic gingival inflammation (periodontitis) triggers a... (Meta-Analysis)
Meta-Analysis Review
Inflammation is a key driver of common noncommunicable diseases. Among common triggers of inflammation, chronic gingival inflammation (periodontitis) triggers a consistent humoral host inflammatory response, but little is known on its impact on circulating inflammatory cell profiles. We aimed to systematically appraise all the evidence linking periodontitis and its treatment to circulating inflammatory cell profiles. From 6 databases, 157 studies were eligible for qualitative synthesis and 29 studies for meta-analysis. Our meta-analysis showed that participants with periodontitis exhibited a significant mean increase in circulating CD4 , CD4 CD45RO , IFNγ-expressing CD4 and CD8 T cells, CD19 CD27 and CD5 B cells, CD14 CD16 monocytes, and CD16 neutrophils but decrease in CD8 T and CD14 CD16 monocytes. Our qualitative synthesis revealed that peripheral blood neutrophils of patients with periodontitis consistently showed elevated production of reactive oxygen species (ROS) when compared with those of healthy controls. Some evidence suggested that the treatment of periodontitis reversed the exaggerated ROS production, but limited and inconclusive data were found on several circulating inflammatory cell profiling. We conclude that periodontitis and its treatment are associated with minor but consistent alterations in circulating inflammatory cell profiles. These changes could represent key mechanisms explaining the association of periodontitis with other comorbidities such as cardiovascular disease, diabetes, and rheumatoid arthritis.
Topics: CD8-Positive T-Lymphocytes; Humans; Inflammation; Monocytes; Periodontitis; Reactive Oxygen Species
PubMed: 35199874
DOI: 10.1002/JLB.5RU1021-524R -
Progress in Neuro-psychopharmacology &... Jul 2023Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with cognitive, social, and academic impairment. Neurotrophins, particularly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with cognitive, social, and academic impairment. Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), have been implicated in the pathophysiology of ADHD and response to stimulant treatment. This review aims to investigate the relationship between BDNF levels in ADHD before and after treatment with stimulants in childhood.
METHODS
This systematic review followed PRISMA-P guidelines and included 19 studies from PubMed, EMBASE, Cochrane, Capes Periodic, and Lilacs databases. The studies were evaluated for risk of bias and level of evidence.
RESULTS
There was no significant difference in peripheral BDNF levels in ADHD children before or after methylphenidate treatment. Additionally, there was no statistically significant difference in BDNF levels between children with ADHD and controls.
DISCUSSION
Understanding the role of BDNF in ADHD may provide insight into the disorder's pathophysiology and facilitate the development of biological markers for clinical use.
CONCLUSION
Our findings suggest that BDNF levels are not significantly affected by methylphenidate treatment in ADHD children and do not differ from controls.
SYSTEMATIC REVIEW REGISTRATION
"Brain-derived neurotrophic factor (BDNF) levels in children and adolescents before and after stimulant use: a systematic review". Number CRD42021261519.
Topics: Adolescent; Child; Humans; Attention Deficit Disorder with Hyperactivity; Brain-Derived Neurotrophic Factor; Central Nervous System Stimulants; Methylphenidate
PubMed: 37044279
DOI: 10.1016/j.pnpbp.2023.110761 -
Journal of Applied Physiology... May 2024Peripheral vascular dysfunction, measured as flow-mediated dilation (FMD), is present across all phases of stroke recovery and elevates the risk for recurrent... (Meta-Analysis)
Meta-Analysis
Peripheral vascular dysfunction, measured as flow-mediated dilation (FMD), is present across all phases of stroke recovery and elevates the risk for recurrent cardiovascular events. The objective of this systematic review and meta-analysis was to characterize baseline FMD in individuals' poststroke, with consideration for each phase of stroke recovery. Three databases (PubMed, CINAHL, and Embase) were searched between January 1, 2000 and October 12, 2023 for studies that examined baseline FMD in stroke. Three reviewers conducted abstract and full-text screening, data extraction, and quality assessment. A random effects model was used to estimate FMD across studies. Meta-regression was used to examine the impact of age and time since stroke (acute, subacute, chronic) on FMD. Twenty-eight studies with ischemic and hemorrhagic stroke were included. Descriptive statistics for the demographics and FMD values of each study are presented. For the meta-analysis, average estimate FMD was 3.9% (95% CI: 2.5-5.3%). We report a large amount of heterogeneity (Cochrane's Q value <0.001, and = 99.6%). Differences in average age and the time poststroke between studies were not significantly associated with differences in FMD values. Despite the large heterogeneity for FMD values across studies, our primary finding suggests that FMD remains impaired across all phases of stroke. This systematic review and meta-analysis offers invaluable insight into poststroke vascular function. Despite the inherent heterogeneity among the 28 studies analyzed, we report that peripheral vascular dysfunction, as quantified by flow-mediated dilation, exists across all stages of stroke recovery. This finding underscores the importance for interventions that focus on improving vascular health and secondary stroke prevention.
Topics: Humans; Endothelium, Vascular; Stroke; Vasodilation
PubMed: 38482571
DOI: 10.1152/japplphysiol.00601.2023 -
Frontiers in Oncology 2023The overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients....
BACKGROUND
The overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients.
METHODS
The prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes.
RESULTS
For untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% , 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% , 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients ( = 0.02). In addition, the pooled CR rate was 17% (95% , 13-22%), 10% (95% , 5-15%), and 10% (95% , 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% , 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively.
CONCLUSION
This meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.
PubMed: 37384289
DOI: 10.3389/fonc.2023.1127112 -
Frontiers in Immunology 2021Disturbances in the kynurenine pathway have been implicated in the pathophysiology of psychotic and mood disorders, as well as several other psychiatric illnesses. It...
OBJECTIVE
Disturbances in the kynurenine pathway have been implicated in the pathophysiology of psychotic and mood disorders, as well as several other psychiatric illnesses. It remains uncertain however to what extent metabolite levels detectable in plasma or serum reflect brain kynurenine metabolism and other disease-specific pathophysiological changes. The primary objective of this systematic review was to investigate the concordance between peripheral and central (CSF or brain tissue) kynurenine metabolites. As secondary aims we describe their correlation with illness course, treatment response, and neuroanatomical abnormalities in psychiatric diseases.
METHODS
We performed a systematic literature search until February 2021 in PubMed. We included 27 original research articles describing a correlation between peripheral and central kynurenine metabolite measures in preclinical studies and human samples from patients suffering from neuropsychiatric disorders and other conditions. We also included 32 articles reporting associations between peripheral KP markers and symptom severity, CNS pathology or treatment response in schizophrenia, bipolar disorder or major depressive disorder.
RESULTS
For kynurenine and 3-hydroxykynurenine, moderate to strong concordance was found between peripheral and central concentrations not only in psychiatric disorders, but also in other (patho)physiological conditions. Despite discordant findings for other metabolites (mainly tryptophan and kynurenic acid), blood metabolite levels were associated with clinical symptoms and treatment response in psychiatric patients, as well as with observed neuroanatomical abnormalities and glial activity.
CONCLUSION
Only kynurenine and 3-hydroxykynurenine demonstrated a consistent and reliable concordance between peripheral and central measures. Evidence from psychiatric studies on kynurenine pathway concordance is scarce, and more research is needed to determine the validity of peripheral kynurenine metabolite assessment as proxy markers for CNS processes. Peripheral kynurenine and 3-hydroxykynurenine may nonetheless represent valuable predictive and prognostic biomarker candidates for psychiatric disorders.
Topics: Animals; Biomarkers; Blood-Brain Barrier; Brain; Disease Models, Animal; Disease Susceptibility; Humans; Kynurenine; Mental Disorders; Metabolic Networks and Pathways; Phenotype; Prognosis; Research; Tryptophan
PubMed: 34630391
DOI: 10.3389/fimmu.2021.716980 -
Critical Reviews in Oncology/hematology Feb 2024Cancer-related fatigue (CRF) is a distressing side effect of cancer and treatment, affecting both patients during active treatment and survivors, negatively impacting... (Review)
Review
Cancer-related fatigue (CRF) is a distressing side effect of cancer and treatment, affecting both patients during active treatment and survivors, negatively impacting quality of life. While its exact cause remains uncertain, various mechanisms such as immune dysfunction, HPA-axis dysfunction, and treatment toxicity are proposed. Inflammatory biomarkers of CRF have been explored in previous research, but non-inflammatory markers have not been comprehensively studied. This systematic review analysed 33 studies to identify non-inflammatory peripheral blood biomarkers associated with CRF. Promising markers included Hb, blood coagulation factors, BDNF, tryptophan, GAA, mtDNA, platinum, CA125, and cystatin-C. Inconsistent findings were observed for other markers like VEGF, leptin, and stress hormones. Most studies focused on adults. Research in pediatrics is limited. This review showed partial evidence for the inflammaging hypothesis (neurotoxicity due to neuro-inflammation) laying at the basis of CRF. Further research, especially in pediatrics, is needed to confirm this hypothesis and guide future biomarker studies.
Topics: Adult; Humans; Child; Quality of Life; Neoplasms; Biomarkers; Survivors; Fatigue
PubMed: 38141868
DOI: 10.1016/j.critrevonc.2023.104245 -
The Cochrane Database of Systematic... Jul 2022The main complications of elevated systemic blood pressure (BP), coronary heart disease, ischaemic stroke, and peripheral vascular disease, are related to thrombosis... (Review)
Review
BACKGROUND
The main complications of elevated systemic blood pressure (BP), coronary heart disease, ischaemic stroke, and peripheral vascular disease, are related to thrombosis rather than haemorrhage. Therefore, it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated BP.
OBJECTIVES
To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with elevated BP, including elevations in systolic or diastolic BP alone or together. To assess the effects of antiplatelet agents on total deaths or major thrombotic events or both in these patients versus placebo or other active treatment. To assess the effects of oral anticoagulants on total deaths or major thromboembolic events or both in these patients versus placebo or other active treatment.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to January 2021: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 12), Ovid MEDLINE (from 1946), and Ovid Embase (from 1974). The World Health Organization International Clinical Trials Registry Platform and the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) were searched for ongoing trials. SELECTION CRITERIA: RCTs in patients with elevated BP were included if they were ≥ 3 months in duration and compared antithrombotic therapy with control or other active treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data for inclusion criteria, our prespecified outcomes, and sources of bias. They assessed the risks and benefits of antiplatelet agents and anticoagulants by calculating odds ratios (OR), accompanied by the 95% confidence intervals (CI). They assessed risks of bias and applied GRADE criteria. MAIN RESULTS: Six trials (61,015 patients) met the inclusion criteria and were included in this review. Four trials were primary prevention (41,695 patients; HOT, JPAD, JPPP, and TPT), and two secondary prevention (19,320 patients, CAPRIE and Huynh). Four trials (HOT, JPAD, JPPP, and TPT) were placebo-controlled and two studies (CAPRIE and Huynh) included active comparators. Four studies compared acetylsalicylic acid (ASA) versus placebo and found no evidence of a difference for all-cause mortality (OR 0.97, 95% CI 0.87 to 1.08; 3 studies, 35,794 participants; low-certainty evidence). We found no evidence of a difference for cardiovascular mortality (OR 0.98, 95% CI 0.82 to 1.17; 3 studies, 35,794 participants; low-certainty evidence). ASA reduced the risk of all non-fatal cardiovascular events (OR 0.63, 95% CI 0.45 to 0.87; 1 study (missing data in 3 studies), 2540 participants; low-certainty evidence) and the risk of all cardiovascular events (OR 0.86, 95% CI 0.77 to 0.96; 3 studies, 35,794 participants; low-certainty evidence). ASA increased the risk of major bleeding events (OR 1.77, 95% CI 1.34 to 2.32; 2 studies, 21,330 participants; high-certainty evidence). One study (CAPRIE; ASA versus clopidogrel) included patients diagnosed with hypertension (mean age 62.5 years, 72% males, 95% Caucasians, mean follow-up: 1.91 years). It showed no evidence of a difference for all-cause mortality (OR 1.02, 95% CI 0.91 to 1.15; 1 study, 19,143 participants; high-certainty evidence) and for cardiovascular mortality (OR 1.08, 95% CI 0.94 to 1.26; 1 study, 19,143 participants; high-certainty evidence). ASA probably reduced the risk of non-fatal cardiovascular events (OR 1.10, 95% CI 1.00 to 1.22; 1 study, 19,143 participants; high-certainty evidence) and the risk of all cardiovascular events (OR 1.08, 95% CI 1.00 to 1.17; 1 study, 19,143 participants; high-certainty evidence) when compared to clopidogrel. Clopidogrel increased the risk of major bleeding events when compared to ASA (OR 1.35, 95% CI 1.14 to 1.61; 1 study, 19,143 participants; high-certainty evidence). In one study (Huynh; ASA verus warfarin) patients with unstable angina or non-ST-segment elevation myocardial infarction, with prior coronary artery bypass grafting (CABG) were included (mean age 68 years, 79.8% males, mean follow-up: 1.1 year). There was no evidence of a difference for all-cause mortality (OR 0.98, 95% CI 0.06 to 16.12; 1 study, 91 participants; low-certainty evidence). Cardiovascular mortality, non-fatal cardiovascular events, and all cardiovascular events were not available. There was no evidence of a difference for major bleeding events (OR 0.13, 95% CI 0.01 to 2.60; 1 study, 91 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence that antiplatelet therapy modifies mortality in patients with elevated BP for primary prevention. ASA reduced the risk of cardiovascular events and increased the risk of major bleeding events. Antiplatelet therapy with ASA probably reduces the risk of non-fatal and all cardiovascular events when compared to clopidogrel. Clopidogrel increases the risk of major bleeding events compared to ASA in patients with elevated BP for secondary prevention. There is no evidence that warfarin modifies mortality in patients with elevated BP for secondary prevention. The benefits and harms of the newer drugs glycoprotein IIb/IIIa inhibitors, clopidogrel, prasugrel, ticagrelor, and non-vitamin K antagonist oral anticoagulants for patients with high BP have not been studied in clinical trials. Further RCTs of antithrombotic therapy including newer agents and complete documentation of all benefits and harms are required in patients with elevated BP.
Topics: Aged; Humans; Middle Aged; Anticoagulants; Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Hypertension; Platelet Aggregation Inhibitors; Thromboembolism; Thrombosis; Warfarin
PubMed: 35900898
DOI: 10.1002/14651858.CD003186.pub4 -
Annals of Vascular Surgery Feb 2021Patients with peripheral arterial disease (PAD) who suffer from claudication have a low exercise capacity, poor quality of life, and often severe disability. Exercise...
BACKGROUND
Patients with peripheral arterial disease (PAD) who suffer from claudication have a low exercise capacity, poor quality of life, and often severe disability. Exercise and healthy nutrition have been shown to be important factors to prevent disease progression. This systematic review aims to assess the evidence supporting the use of combined nutrition and structured exercise in patients with intermittent claudication.
METHODS
Publications that included a combination of structured exercise (SE) and a nutritional intervention and that reported quality of life, exercise capacity, pain-free walking distance, limb blood flow hemodynamics, need for revascularization surgery, or surgical outcomes were systematically searched. Publications were screened, selected, and reviewed by 2 independent reviewers.
RESULTS
Four publications were found reporting the effects of combined SE and nutrition programs. Pooled statistical analysis across trials was not performed because of the heterogeneity of study designs and type of interventions. Only 2 randomized controlled trials were found, reporting conflicting results with regard to the effects of combined SE and nutrition on exercise capacity. Only one trial reported quality of life measures. Blood flow was increased in the intervention involving inorganic nitrate in addition to SE.
CONCLUSIONS
There are conflicting results and lack of quality data proving the benefit of nutrition and SE programs on patient-centered outcomes and limb blood flow. There are no data on the effects of combined nutrition and exercise on the need for revascularization surgery or postrevascularization outcomes. More randomized controlled trials are needed to assess the effects of multimodal interventions on patient-centered outcomes and clinical outcomes of PAD.
Topics: Aged; Combined Modality Therapy; Diet, Healthy; Exercise; Exercise Therapy; Exercise Tolerance; Female; Functional Status; Humans; Intermittent Claudication; Male; Middle Aged; Nutritive Value; Peripheral Arterial Disease; Quality of Life; Recovery of Function; Regional Blood Flow; Treatment Outcome
PubMed: 33160056
DOI: 10.1016/j.avsg.2020.09.048 -
Frontiers in Immunology 2022Tic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more persistent tic symptoms. The etiological mechanism of TS concerning immune dysfunction remains unclear due to limited evidence, especially for pediatric TS patients.
METHOD
In the present study, a meta-analysis was performed to confirm the identified changes in proinflammatory cytokines and T cells of pediatric TS patients. A total of five databases, including PubMed, Web of Science, PsycINFO, Google Scholar and the China National Knowledge Infrastructure (CNKI), were used for the literature search. The standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval (CI) were used to present the effect size of each type of proinflammatory cytokine and T cell. Sensitivity analysis, subgroup analysis and meta-regression analysis were used to explore the heterogeneity of the meta-analysis. This meta-analysis was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021110079).
RESULTS
In the 25 studies included in this meta-analysis, thirteen studies focused on the levels of T cells, and twelve studies focused on the levels of proinflammatory cytokines. Based on the random-effects model, the pooled MDs are -1.45 (95% CI: -3.44, 0.54) for CD3 cells, -4.44 (95% CI: -6.80, -2.08) for CD4 cells, and 1.94 (95% CI: -0.08, 3.97) for CD8 cells. The pooled SMDs are1.36 for IL-6 (95% CI: 0.00, 2.72) and 2.39 for tumor necrosis factor alpha (TNF-α) (95% CI: 0.93, 3.84).
CONCLUSION
We provided evidence of immune dysfunction in pediatric TS patients, with elevated levels of particular proinflammatory cytokines and disproportionate changes in T-cell subpopulations. Small to large effect sizes were identified for increased IL-6 levels as well as a reduced number of T helper cells, while a large effect size was identified for increased TNF-α levels. These results indicate a close association between peripheral immune activation and TS. However, the most direct and meaningful interaction between peripheral immune status and microglial activation in the central nervous system in TS patients requires further exploration.
Topics: Child; Cytokines; Humans; Interleukin-6; T-Lymphocytes; Tourette Syndrome; Tumor Necrosis Factor-alpha
PubMed: 35693824
DOI: 10.3389/fimmu.2022.843247 -
Frontiers in Neuroscience 2019Guillain Barré Syndrome (GBS) is an autoimmune disorder caused by the immune-mediated damage of the peripheral nervous system. Increasing evidence suggests that...
Guillain Barré Syndrome (GBS) is an autoimmune disorder caused by the immune-mediated damage of the peripheral nervous system. Increasing evidence suggests that inflammatory cytokines are important mediators for the onset and progression of GBS. A number of clinical studies have demonstrated elevated levels of T helper-1 (Th1-), Th2-, and Th17-related cytokines in patients with GBS; however, the results were inconsistent across studies. We performed a systematic review and a meta-analysis of studies comparing the levels of inflammatory cytokines in the cerebrospinal fluid and peripheral blood between patients with GBS and healthy individuals, using Comprehensive Meta-Analysis Version 2 software. A database search identified 30 studies comprising 1,302 patients with GBS and 1,073 healthy controls. The random-effects meta-analysis demonstrated that peripheral blood tumor necrosis factor-α (Hedges g, 1.544; 95% confidence interval (CI), 0.923-2.165; < 0.001), interleukin-1β (IL-1β; Hedges g, 0.678; 95% CI, 0.183-1.172; = 0.007), IL-6 (Hedges g, 0.630; 95% CI, 0.100-1.160; = 0.02), IL-4 (Hedges g, 0.822; 95% CI, 0.220-1.423; = 0.007), IL-17 (Hedges g, 1.452; 95% CI, 0.331-2.573; = 0.011), interferon-γ (Hedges g, 1.104; 95% CI, 0.490-1.719; < 0.001), and C-reactive protein (Hedges g, 0.909; 95% CI, 0.453-1.365; < 0.001) levels were significantly increased in patients with GBS when compared with healthy controls. Contrastingly, the blood IL-10 and transforming growth factor-β levels were not significantly associated with GBS. Furthermore, the meta-analysis found that cerebrospinal fluid IL-17 levels were significantly associated with GBS (Hedges g, 1.882; 95% CI, 0.104-3.661; = 0.038). Altogether, our results clarified the circulating inflammatory cytokine profile in patients with GBS, and revealed that Th1-, Th2-, and Th17-related cytokines were highly elevated in the GBS patients, suggesting the potential use of these cytokines as biomarkers for GBS.
PubMed: 31379477
DOI: 10.3389/fnins.2019.00717