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Alzheimer's Research & Therapy Oct 2023Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years... (Review)
Review
Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years from the initial diagnosis. Diagnosis of cognitive impairment in dementia is typically based on clinical evaluation, neuropsychological assessments, cerebrospinal fluid (CSF) biomarkers, and neuroimaging. The main goal of diagnosing MCI is to determine its cause, particularly whether it is due to Alzheimer's disease (AD). However, only a limited percentage of the population has access to etiological confirmation, which has led to the emergence of peripheral fluid biomarkers as a diagnostic tool for dementias, including MCI due to AD. Recent advances in biofluid assays have enabled the use of sophisticated statistical models and multimodal machine learning (ML) algorithms for the diagnosis of MCI based on fluid biomarkers from CSF, peripheral blood, and saliva, among others. This approach has shown promise for identifying specific causes of MCI, including AD. After a PRISMA analysis, 29 articles revealed a trend towards using multimodal algorithms that incorporate additional biomarkers such as neuroimaging, neuropsychological tests, and genetic information. Particularly, neuroimaging is commonly used in conjunction with fluid biomarkers for both cross-sectional and longitudinal studies. Our systematic review suggests that cost-effective longitudinal multimodal monitoring data, representative of diverse cultural populations and utilizing white-box ML algorithms, could be a valuable contribution to the development of diagnostic models for AD due to MCI. Clinical assessment and biomarkers, together with ML techniques, could prove pivotal in improving diagnostic tools for MCI due to AD.
Topics: Humans; Alzheimer Disease; Cross-Sectional Studies; Disease Progression; Cognitive Dysfunction; Biomarkers; Machine Learning; Amyloid beta-Peptides; tau Proteins
PubMed: 37838690
DOI: 10.1186/s13195-023-01304-8 -
Arquivos Brasileiros de Cardiologia Mar 2023Central blood pressure (cBP) is considered an independent predictor of organ damage, cardiovascular events and all-cause mortality. Evidence has shown that high... (Meta-Analysis)
Meta-Analysis
Central blood pressure (cBP) is considered an independent predictor of organ damage, cardiovascular events and all-cause mortality. Evidence has shown that high intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness and vascular function. However, the effects of these aerobic training modalities on cBP have not yet been properly reviewed.This meta-analysis aims to investigate to effects of HIIT versus MICT on cBP.We conducted a meta-analysis of randomized controlled trials that compared HIIT versus MICT on cBP. Primary outcomes were measures of central systolic blood pressure (cSBP) and central diastolic blood pressure (cDBP). Peripheral systolic blood pressure (pSBP) and diastolic blood pressure (pDBP), pulse wave velocity (PWV) and maximal oxygen uptake (VO2max) were analyzed as second outcomes. Meta-analysis of mean differences (MD) was conducted using the random effects model.Our study included 163 patients enrolled in six trials. We found that HIIT was superior to MICT in reducing the cSBP (MD = -3.12 mmHg, 95% CI: -4.75 to -1.50, p = 0.0002) and SBP (MD = -2.67 mmHg, 95% CI: -5.18 to -0.16, p = 0.04), and increasing VO2max(MD = 2.49 mL/kg/min, 95% CI: 1.25 to 3.73, p = 0.001). However, no significant differences were reported for cDBP, DBP and PWV.HIIT was superior to MICT in reducing the cSBP, which suggests its potential role as a non-pharmacological therapy for high blood pressure.
Topics: Humans; Blood Pressure; High-Intensity Interval Training; Pulse Wave Analysis; Hypertension; Cardiorespiratory Fitness
PubMed: 37098987
DOI: 10.36660/abc.20220398 -
Psychiatry Investigation Dec 2022Immune system dysregulation is hypothesised to be central to the aetiopathogenesis of schizophrenia; however, the role of sterile inflammation remains unclear. Damage...
OBJECTIVE
Immune system dysregulation is hypothesised to be central to the aetiopathogenesis of schizophrenia; however, the role of sterile inflammation remains unclear. Damage associated molecular patterns are key initiators of sterile inflammation and are detectable in peripheral blood.
METHODS
A defined systematic search of the Web of Science, PubMed, and Scopus was performed to identify adult case-control studies published between January 1990 and June 2022. Three studies consisting of 242 cases and 83 controls met inclusion for the systematic review and meta-analysis of HMGB1 while twenty-eight studies consisting of 1,544 cases and 1,248 healthy controls were included for S100B.
RESULTS
A significant standardised mean difference in peripheral S100B and HMGB1 concentrations was detected between cases and controls. S100B subgroup analysis determined the largest significant effect size for unmedicated individuals diagnosed with schizophrenia.
CONCLUSION
This study provides evidence that peripheral S100B and HMGB1 concentrations are elevated in individuals diagnosed with schizophrenia when compared with healthy controls. These results should be interpreted with caution as significant heterogeneity was present during meta-analysis of S100B in the entire sample and in sub-group analysis. The persistence of significant heterogeneity throughout subgroup analysis indicates that the current diagnostic groupings may be a barrier to understanding human behaviours and emotions.
PubMed: 36588432
DOI: 10.30773/pi.2022.0173 -
Sports Medicine - Open Sep 2022The implementation of blood flow restriction (BFR) during exercise is becoming an increasingly useful adjunct method in both athletic and rehabilitative settings....
BACKGROUND
The implementation of blood flow restriction (BFR) during exercise is becoming an increasingly useful adjunct method in both athletic and rehabilitative settings. Advantages in pairing BFR with training can be observed in two scenarios: (1) training at lower absolute intensities (e.g. walking) elicits adaptations akin to high-intensity sessions (e.g. running intervals); (2) when performing exercise at moderate to high intensities, higher physiological stimulus may be attained, leading to larger improvements in aerobic, anaerobic, and muscular parameters. The former has been well documented in recent systematic reviews, but consensus on BFR (concomitant or post-exercise) combined with high-intensity interval training (HIIT) protocols is not well established. Therefore, this systematic review evaluates the acute and chronic effects of BFR + HIIT.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify relevant studies. A systematic search on 1 February 2022, was conducted on four key databases: ScienceDirect, PubMed, Scopus and SPORTDiscus. Quality of each individual study was assessed using the Physiotherapy Evidence Database (PEDro) scale. Extraction of data from included studies was conducted using an adapted version of the 'Population, Intervention, Comparison, Outcome' (PICO) framework.
RESULTS
A total of 208 articles were identified, 18 of which met inclusion criteria. Of the 18 BFR + HIIT studies (244 subjects), 1 reported both acute and chronic effects, 5 examined acute responses and 12 investigated chronic effects. Acutely, BFR challenges the metabolic processes (vascular and oxygenation responses) during high-intensity repeated sprint exercise-which accelerates central and peripheral neuromuscular fatigue mechanisms resulting in performance impairments. Analysis of the literature exploring the chronic effects of BFR + HIIT suggests that BFR does provide an additive physiological training stimulus to HIIT protocols, especially for measured aerobic, muscular, and, to some extent, anaerobic parameters.
CONCLUSION
Presently, it appears that the addition of BFR into HIIT enhances physiological improvements in aerobic, muscular, and, to some extent, anaerobic performance. However due to large variability in permutations of BFR + HIIT methodologies, it is necessary for future research to explore and recommend standardised BFR guidelines for each HIIT exercise type.
PubMed: 36178530
DOI: 10.1186/s40798-022-00506-y -
Frontiers in Neurology 2020Within the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from...
Within the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings.
PubMed: 33613412
DOI: 10.3389/fneur.2020.577312 -
The Journal of Headache and Pain Apr 2023The role of inflammation and cytokines in the pathophysiology of primary headache disorders is uncertain. We performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of inflammation and cytokines in the pathophysiology of primary headache disorders is uncertain. We performed a systematic review and meta-analysis to synthesise the results of studies comparing peripheral blood cytokine levels between patients with migraine, tension-type headache, cluster headache, or new daily persistent headache (NDPH), and healthy controls; and in migraine between the ictal and interictal stages.
METHODS
We searched PubMed/Medline and Embase from inception until July 2022. We included original research studies which measured unstimulated levels of any cytokines in peripheral blood using enzyme-linked immunosorbent assay or similar assay. We assessed risk of bias using the Newcastle-Ottawa Quality Assessment Scale. We used random effects meta-analysis with inverse variance weighted average to calculate standardised mean difference (SMD), 95% confidence intervals, and heterogeneity for each comparison. This study is registered with PROSPERO (registration number CRD42023393363). No funding was received for this study.
RESULTS
Thirty-eight studies, including 1335 patients with migraine (32 studies), 302 with tension-type headache (nine studies), 42 with cluster headache (two studies), and 1225 healthy controls met inclusion criteria. Meta-analysis showed significantly higher interleukin (IL)-6 (SMD 1.07, 95% CI 0.40-1.73, p = 0.002), tumour necrosis factor (TNF)-α (SMD 0.61, 95% CI 0.14-1.09, p = 0.01), and IL-8 (SMD 1.56, 95% CI 0.03-3.09, p = 0.04), in patients with migraine compared to healthy controls, and significantly higher interleukin-1β (IL-1β) (SMD 0.34, 95% CI 0.06-0.62, p = 0.02) during the ictal phase of migraine compared to the interictal phase. Transforming growth factor (TGF)-β (SMD 0.52, 95% CI 0.18-0.86, p = 0.003) and TNF-α (SMD 0.64, 95% CI 0.33-0.96, p = 0.0001) were both higher in patients with tension-type headache than controls.
CONCLUSIONS
The higher levels of the proinflammatory cytokines IL-6, IL-8 and TNF-α in migraine compared to controls, and IL-1β during the ictal stage, suggest a role for inflammation in the pathophysiology of migraine, however prospective studies are required to confirm causality and investigate the mechanisms for the increase in cytokine levels identified. Cytokines may also have a role in tension-type headache. Due a lack of data, no conclusions can be made regarding cluster headache or NDPH.
Topics: Humans; Cytokines; Tension-Type Headache; Tumor Necrosis Factor-alpha; Cluster Headache; Interleukin-8; Migraine Disorders; Inflammation
PubMed: 37016284
DOI: 10.1186/s10194-023-01572-7 -
European Respiratory Review : An... Sep 2023Peripheral blood monocyte counts have been associated with poor outcomes in interstitial lung disease (ILD). However, studies are limited by variable biomarker... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral blood monocyte counts have been associated with poor outcomes in interstitial lung disease (ILD). However, studies are limited by variable biomarker thresholds, analytic approaches and heterogenous populations. This systematic review and meta-analysis characterised the relationship between monocytes and clinical outcomes in ILD.
METHODS
Electronic database searches were performed. Two reviewers screened abstracts and extracted data. Pooled estimates (hazard ratios (HRs)) of monocyte count thresholds were calculated for their association with mortality using ≥0.6×10 and >0.9×10 cells·L for unadjusted models and ≥0.95×10 cells·L for adjusted models, using random effects, with heterogeneity and bias assessed. Disease progression associated with monocytes >0.9×10cells·L was also calculated.
RESULTS
Of 3279 abstracts, 13 were included in the systematic review and eight in the meta-analysis. The pooled unadjusted HR for mortality for monocyte counts ≥0.6×10 cells·L was 1.71 (95% CI 1.34-2.19, p<0.001, I=0%) and for monocyte counts >0.90×10 cells·L it was 2.44 (95% CI 1.53-3.87, p=0.0002, I=52%). The pooled adjusted HR for mortality for monocyte counts ≥0.95×10 cells·L was 1.93 (95% CI 1.24-3.01, p=0.0038 I=69%). The pooled HR for disease progression associated with increased monocyte counts was 1.83 (95% CI 1.40-2.39, p<0.0001, I=28%).
CONCLUSIONS
Peripheral blood monocyte counts were associated with an increased risk of mortality and disease progression in patients with ILD.
Topics: Humans; Monocytes; Lung Diseases, Interstitial; Patients; Disease Progression
PubMed: 37673424
DOI: 10.1183/16000617.0072-2023 -
Mutation Research. Genetic Toxicology... Oct 2023Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and... (Meta-Analysis)
Meta-Analysis Review
Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and PubChem databases to identify publications relevant to this question. Micronucleus formation was the genotoxicity endpoint. Three publications comparing exposed vs. non-exposed individuals are included in this analysis; the exposures were to ethylene oxide or ionising radiation (atomic bomb, thorotrast, or radioiodine therapy). Information was extracted on the types of exposure, the numbers of participants, and the micronucleus frequencies. Relative differences (odds ratios) and absolute differences (risk differences) in the numbers of micronuclei between exposed and non-exposed persons were calculated separately for individual cell types (peripheral blood and bone marrow). Random effects meta-analyses for the relative differences in cell abnormalities were performed. The results showed very small differences in the frequencies of micronuclei between exposed and non-exposed individuals, as measured in either peripheral blood or bone marrow cell populations, on both absolute and relative scales. No definite conclusion concerning the relative sensitivities of bone marrow and peripheral blood cells can be made, based on these publications.
Topics: Humans; Bone Marrow; Iodine Radioisotopes; Micronucleus Tests; Blood Cells; Bone Marrow Cells; DNA Damage; Micronuclei, Chromosome-Defective
PubMed: 37770146
DOI: 10.1016/j.mrgentox.2023.503689 -
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 -
European Journal of Vascular and... Nov 2022The role of antithrombotic therapy in the management of aortic and peripheral aneurysms is unclear. This systematic review and meta-analysis aimed to assess the impact... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The role of antithrombotic therapy in the management of aortic and peripheral aneurysms is unclear. This systematic review and meta-analysis aimed to assess the impact of antithrombotics on clinical outcomes for aortic and peripheral aneurysms.
METHODS
Medline, Embase, and CENTRAL databases were searched. Randomised controlled trials and observational studies investigating the effect of antithrombotic therapy on clinical outcomes for patients with any aortic or peripheral artery aneurysm were included.
RESULTS
Fifty-nine studies (28 with antiplatelet agents, 12 anticoagulants, two intra-operative heparin, and 16 any antithrombotic agent) involving 122 102 patients were included. Abdominal aortic aneurysm (AAA) growth rate was not significantly associated with the use of antiplatelet therapy (SMD -0.36 mm/year; 95% CI -0.75 - 0.02; p = .060; GRADE certainty: very low). Antithrombotics were associated with increased 30 day mortality for patients with AAAs undergoing intervention (OR 2.30; 95% CI 1.51 - 3.51; p < .001; GRADE certainty: low). Following intervention, antiplatelet therapy was associated with reduced long term all cause mortality (HR 0.84; 95% CI 0.76 - 0.92; p < .001; GRADE certainty: moderate), whilst anticoagulants were associated with increased all cause mortality (HR 1.64; 95% CI 1.14 - 2.37; p = .008; GRADE certainty: very low), endoleak within three years (OR 1.99; 95% CI 1.10 - 3.60; p = .020; I = 60%; GRADE certainty: very low), and an increased re-intervention rate at one year (OR 3.25; 95% CI 1.82 - 5.82; p < .001; I = 35%; GRADE certainty: moderate). Five studies examined antithrombotic therapy for popliteal aneurysms. Meta-analysis was not possible due to heterogeneity.
CONCLUSIONS
There was a lack of high quality data examining antithrombotic therapy for patients with aneurysms. Antiplatelet therapy was associated with a reduction in post-intervention all cause mortality for AAA, whilst anticoagulants were associated with an increased risk of all cause mortality, endoleak, and re-intervention. Large, well designed trials are still required to determine the therapeutic benefits of antithrombotic agents in this setting.
Topics: Humans; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Endoleak; Aortic Aneurysm, Abdominal; Anticoagulants
PubMed: 35853579
DOI: 10.1016/j.ejvs.2022.07.008