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Cells Apr 2023With the development of new technologies capable of detecting low concentrations of Alzheimer's disease (AD) relevant biomarkers, the idea of a blood-based diagnosis of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
With the development of new technologies capable of detecting low concentrations of Alzheimer's disease (AD) relevant biomarkers, the idea of a blood-based diagnosis of AD is nearing reality. This study aims to consider the evidence of total and phosphorylated tau as blood-based biomarkers for mild cognitive impairment (MCI) and AD when compared to healthy controls.
METHODS
Studies published between 1 January 2012 and 1 May 2021 (Embase and MEDLINE databases) measuring plasma/serum levels of tau in AD, MCI, and control cohorts were screened for eligibility, including quality and bias assessment via a modified QUADAS. The meta-analyses comprised 48 studies assessing total tau (t-tau), tau phosphorylated at threonine 181 (p-tau181), and tau phosphorylated at threonine 217 (p-tau217), comparing the ratio of biomarker concentrations in MCI, AD, and cognitively unimpaired (CU) controls.
RESULTS
Plasma/serum p-tau181 (mean effect size, 95% CI, 2.02 (1.76-2.27)) and t-tau (mean effect size, 95% CI, 1.77 (1.49-2.04)) were elevated in AD study participants compared to controls. Plasma/serum p-tau181 (mean effect size, 95% CI, 1.34 (1.20-1.49)) and t-tau (mean effect size, 95% CI, 1.47 (1.26-1.67)) were also elevated with moderate effect size in MCI study participants compared to controls. p-tau217 was also assessed, albeit in a small number of eligible studies, for AD vs. CU (mean effect size, 95% CI, 1.89 (1.86-1.92)) and for MCI vs. CU groups (mean effect size, 95% CI, 4.16 (3.61-4.71)).
CONCLUSIONS
This paper highlights the growing evidence that blood-based tau biomarkers have early diagnostic utility for Alzheimer's disease.
REGISTRATION
PROSPERO No. CRD42020209482.
Topics: Humans; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; tau Proteins
PubMed: 37190093
DOI: 10.3390/cells12081184 -
Frontiers in Physiology 2022Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of...
Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of overtraining. Hormonal alterations associated with intensified training, such as blunted cortisol, may impair the immune response. Cortisol promotes the maturation and migration of dendritic cells which subsequently stimulate the T cell response. However, there are currently no clear reliable biomarkers to highlight the overtraining syndrome. This systematic review and meta-analysis examined the effect of intensified training on immune cells. Outcomes from this could provide insight into whether these markers may be used as an indicator of negative states of overtraining. SPORTDiscus, PUBMED, Academic Search Complete, Scopus and Web of Science were searched until June 2022. Included articles reported on immune biomarkers relating to lymphocytes, dendritic cells, and cytokines before and after a period of intensified training, in humans and rodents, at rest and in response to exercise. 164 full texts were screened for eligibility. Across 57 eligible studies, 16 immune biomarkers were assessed. 7 were assessed at rest and in response to a bout of exercise, and 9 assessed at rest only. Included lymphocyte markers were CD3, CD4 and CD8 T cell count, NK cell count, NK Cytolytic activity, lymphocyte proliferation and CD4/CD8 ratio. Dendritic cell markers examined were CD80, CD86, and MHC II expression. Cytokines included IL-1β, IL-2, IL-10, TNF-α and IFN-γ. A period of intensified training significantly decreased resting total lymphocyte (0.57, 95% CI 0.30) and CD8 T cell counts (0.37, 95% CI 0.04), and unstimulated plasma IL-1β levels (0.63, 95% CI 0.17). Resting dendritic cell CD86 expression significantly increased ( 2.18, 95% CI 4.07). All other biomarkers remained unchanged. Although some biomarkers alter after a period of intensified training, definitive immune biomarkers are limited. Specifically, due to low study numbers, further investigation into the dendritic cell response in human models is required.
PubMed: 36439269
DOI: 10.3389/fphys.2022.998925 -
Molecular Diagnosis & Therapy May 2023MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains uncertain because of insufficient data.
METHODS
We conducted a literature search in PubMed, Embase, and Web of Science databases to obtain relevant articles and extract data to evaluate the role of microRNA-155 in cancer diagnosis and prognosis.
RESULTS
The pooled results showed that microRNA-155 presented a remarkable diagnostic value in cancers (area under the curve = 0.90, 95% confidence interval (CI 0.87-0.92; sensitivity = 0.83, 95% CI 0.79-0.87; specificity = 0.83, 95% CI 0.80-0.86), which was maintained in the subgroups stratified by ethnicity (Asian and Caucasian), cancer types (breast cancer, lung cancer, hepatocellular carcinoma, leukemia, and pancreatic ductal adenocarcinoma), sample types (plasma, serum, tissue), and sample size (n >100 and n <100). In prognosis, a combined hazard ratio (HR) showed that microRNA-155 was significantly associated with poor overall survival (HR = 1.38, 95% CI 1.25-1.54) and recurrence-free survival (HR = 2.13, 95% CI 1.65-2.76), and was boundary significant with poor progression-free survival (HR = 1.20, 95% CI 1.00-1.44), but not significant with disease-free survival (HR = 1.14, 95% CI 0.70-1.85). Subgroup analyses in overall survival showed that microRNA-155 was associated with poor overall survival in the subgroups stratified by ethnicity and sample size. However, the significant association was maintained in cancer types subgroups of leukemia, lung cancer, and oral squamous cell carcinoma, but not in colorectal cancer, hepatocellular carcinoma, and breast cancer, and was maintained in sample types subgroups of bone marrow and tissue, but not in plasma and serum.
CONCLUSIONS
Results from this meta-analysis demonstrated that microRNA-155 was a valuable biomarker in cancer diagnosis and prognosis.
Topics: Humans; Female; MicroRNAs; Carcinoma, Hepatocellular; Prognosis; Carcinoma, Squamous Cell; Mouth Neoplasms; Pancreatic Neoplasms; Lung Neoplasms; Breast Neoplasms; Leukemia; Liver Neoplasms; Biomarkers, Tumor
PubMed: 36939982
DOI: 10.1007/s40291-023-00641-6 -
Heliyon Feb 2024Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated...
BACKGROUND
Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications.
METHODS
In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464).
RESULTS
Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels.
CONCLUSION
These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.
PubMed: 38356516
DOI: 10.1016/j.heliyon.2024.e25537 -
Seminars in Thrombosis and Hemostasis Jul 2021Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic...
Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic review, we provide an overview and discussion of the current literature in regards to clinical manifestations, diagnosis, and treatment of altered fibrinolysis in patients suffering from hematological malignancies, beyond acute promyelocytic leukemia. We performed a systematic literature search employing the databases Pubmed, Embase, and Web of Science to identify original studies investigating fibrinolysis in hematological malignancies. Studies investigating fibrinolysis in acute promyelocytic leukemia or disseminated intravascular coagulation were excluded. We identified 32 studies fulfilling the inclusion criteria. A majority of the studies were published more than two decades ago, and none of the studies examined all available markers of fibrinolysis or used dynamic clot lysis assays. In acute leukemia L-asparaginase treatment induced a hypofibrinolytic state, and prior to chemotherapy there seemed to be little to no change in fibrinolysis. In studies examining fibrinolysis during chemotherapy results were ambiguous. Two studies examining multiple myeloma indicated hypofibrinolysis prior to chemotherapy, and in another plasma cell disease, amyloid light chain-amyloidosis, clear signs of hyperfibrinolysis were demonstrated. In myeloproliferative neoplasms, the studies reported signs of hypofibrinolysis, in line with the increased risk of thrombosis in this disease. Only one study regarding lymphoma was identified, which indicated no alterations in fibrinolysis. In conclusion, this systematic review demonstrated that only sparse, and mainly old, evidence exists on fibrinolysis in hematological malignancy. However, the published studies showed a tendency toward hypofibrinolysis in myeloproliferative disorders, an increased risk of hyperfibrinolysis, and bleeding in patients with AL-amyloidosis, whereas studies regarding acute leukemias were inconclusive except with regard to L-asparaginase treatment, which induced a hypofibrinolytic state.
Topics: Amyloidosis; Asparaginase; Blood Coagulation Disorders; Fibrinolysis; Hematologic Neoplasms; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Thrombosis
PubMed: 34058766
DOI: 10.1055/s-0041-1725099 -
Translational Cancer Research Mar 2022Multiple myeloma (MM) is a malignant tumor originating from plasma cells in the bone marrow. The existing treatment methods can prolong the survival time of patients,...
Efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy in the treatment of relapsed and refractory multiple myeloma: a systematic-review and meta-analysis of clinical trials.
BACKGROUND
Multiple myeloma (MM) is a malignant tumor originating from plasma cells in the bone marrow. The existing treatment methods can prolong the survival time of patients, but they still face the problems of myeloma relapse and refractory disease. Chimeric antigen receptor (CAR)-T cell therapy is a new cellular immunotherapy that can target and recognize antigens and kill tumor cells but the efficacy and safety data varied in different studies. We performed this systematic review and meta-analysis to understand its efficacy and safety.
METHODS
Literature published from January 2015 to November 2021 was obtained by searching the keywords "CAR-T", "CAR-T Cell", and "Multiple Myeloma" by computer using the Embase, PubMed, Web of Science, and Cochrane library databases according to the PICOS (Participants, Interventions, Comparisons, Outcomes, Study type) criteria. The quality of the literature was assessed by the Joanna Briggs Institute (JBI) Critical Appraisal Tool for prevalence studies. The complete response rate, the incidence of cytokine release syndrome (CRS) above grade 3, and the overall incidence of adverse reactions were used as the outcome indicators. The pooled rates were performed and analyzed using the R language toolkit.
RESULTS
A total of 10 studies including 353 study cases were included. Meta-analysis showed that the pooled complete response rate of CAR-T therapy in the treatment of MM was 0.55, 95% confidence interval (CI): (0.50, 0.60), the pooled incidence of CRS was 0.55, 95% CI: (0.50, 0.60), and the pooled incidence of serious adverse reactions was 0.92, 95% CI: (0.88, 0.95). Subgroup analysis was performed based on antigen types or costimulatory molecules, and there was no significant difference in the efficacy of CAR-T and the incidence of CRS between the two subgroups (P>0.05).
CONCLUSIONS
As a new immunotherapy strategy with great potential, CAR-T has a significant effect in the treatment of MM, but its safety needs to be further improved. The types of costimulatory molecules and CAR-T antigens can affect its efficacy and safety.
PubMed: 35402175
DOI: 10.21037/tcr-22-344 -
Critical Care (London, England) Nov 2012Early diagnosis of sepsis is vital to the clinical course and outcome of septic patients. Recently, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Early diagnosis of sepsis is vital to the clinical course and outcome of septic patients. Recently, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) appears to be a potential marker of infection. The objective of this systematic review and meta-analysis was to evaluate the accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients.
METHODS
A systematic literature search of PubMed, Embase and Cochrane Central Register of Controlled Trials was performed using specific search terms (up to 15 October 2012). Studies were included if they assessed the accuracy of plasma sTREM-1 for sepsis diagnosis in adult patients with systemic inflammatory response syndrome (SIRS) and provided sufficient information to construct a 2 X 2 contingency table.
RESULTS
Eleven studies with a total of 1,795 patients were included. The pooled sensitivity and specificity was 79% (95% confidence interval (CI), 65 to 89) and 80% (95% CI, 69 to 88), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 4.0 (95% CI, 2.4 to 6.9), 0.26 (95% CI, 0.14 to 0.48), and 16 (95% CI, 5 to 46), respectively. The area under the curve of the summary receiver operator characteristic was 0.87 (95% CI, 0.84 to 0.89). Meta-regression analysis suggested that patient sample size and assay method were the main sources of heterogeneity. Publication bias was suggested by an asymmetrical funnel plot (P = 0.02).
CONCLUSIONS
The present meta-analysis showed that plasma sTREM-1 had a moderate diagnostic performance in differentiating sepsis from SIRS. Accordingly, plasma sTREM-1 as a single marker was not sufficient for sepsis diagnosis in systemic inflammatory patients.
Topics: Adult; Biomarkers; Humans; Membrane Glycoproteins; Receptors, Immunologic; Reproducibility of Results; Sensitivity and Specificity; Systemic Inflammatory Response Syndrome; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 23194114
DOI: 10.1186/cc11884 -
Pediatric Emergency Care Aug 2018Balanced resuscitation of plasma, platelets, and red blood cells is now recognized as improving outcomes in traumatic bleeding in adults. The correct approach in... (Review)
Review
INTRODUCTION
Balanced resuscitation of plasma, platelets, and red blood cells is now recognized as improving outcomes in traumatic bleeding in adults. The correct approach in children has yet to be determined.
METHODS
We performed a systematic review of the literature into transfusion protocols in traumatic hemorrhage in children by conducting an article search of significant databases to identify relevant articles. Studies of interest included interventional trials with comparisons relating to the transfusion of blood including blood component therapy. The search identified 422 articles of interest, the abstracts of which were independently reviewed by 2 authors for inclusion in the trial. This revealed 35 articles, the full texts of which were reviewed. There were no randomized controlled trials and 4 nonrandomized trials with a further 21 articles that were deemed relevant. The data were insufficient for meta-analysis, and so a descriptive analysis was performed.
RESULTS
There were 4 main trials. Two trials were small (approximately 100 patients) nonrandomized trials into pediatric hemorrhage managed as per a massive transfusion protocol or at physician discretion. One was a retrospective analysis of pediatric trauma patients who received red blood cell transfusion with differing platelet ratios, and one was a trauma database review of component ratios in hemorrhaging children. All 4 trials found increased ratios had no effect on mortality.
DISCUSSION
As well as blood component therapy, adjunctive therapies used in the management of bleeding children are discussed. These include tranexamic acid, viscoelastic hemostatic assays, factor VIIa, and fibrinogen use.
CONCLUSIONS
There is little evidence for improved outcomes using component-based transfusion in a rigid 1:1:1 strategy in children. A goal-directed approach using viscoelastic hemostatic assay-guided treatment with early institution of tranexamic acid and fibrinogen replacement is considered the way forward.
Topics: Adult; Blood Transfusion; Child; Hemorrhage; Humans; Survival Rate; Wounds and Injuries
PubMed: 30080793
DOI: 10.1097/PEC.0000000000001570 -
Movement Disorders : Official Journal... Sep 2023Parkinson's disease (PD) biomarkers are needed by both clinicians and researchers (for diagnosis, identifying study populations, and monitoring therapeutic response).... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) biomarkers are needed by both clinicians and researchers (for diagnosis, identifying study populations, and monitoring therapeutic response). Imaging, genetic, and biochemical biomarkers have been widely studied. In recent years, extracellular vesicles (EVs) have become a promising material for biomarker development. Proteins and molecular material from any organ, including the central nervous system, can be packed into EVs and transported to the periphery into easily obtainable biological specimens like blood, urine, and saliva. We performed a systematic review and meta-analysis of articles (published before November 15, 2022) reporting biomarker assessment in EVs in PD patients and healthy controls (HCs). Biomarkers were analyzed using random effects meta-analysis and the calculated standardized mean difference (Std.MD). Several proteins and ribonucleic acids have been identified in EVs in PD patients, but only α-synuclein (aSyn) and leucine-rich repeat kinase 2 (LRRK2) were reported in sufficient studies (n = 24 and 6, respectively) to perform a meta-analysis. EV aSyn was significantly increased in neuronal L1 cell adhesion molecule (L1CAM)-positive blood EVs in PD patients compared to HCs (Std.MD = 1.84, 95% confidence interval = 0.76-2.93, P = 0.0009). Further analysis of the biological sample and EV isolation method indicated that L1CAM-IP (immunoprecipitation) directly from plasma was the best isolation method for assessing aSyn in PD patients. Upcoming neuroprotective clinical trials immediately need peripheral biomarkers for identifying individuals at risk of developing PD. Overall, the improved sensitivity of assays means they can identify biomarkers in blood that reflect changes in the brain. CNS-derived EVs in blood will likely play a major role in biomarker development in the coming years. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; alpha-Synuclein; Biomarkers; Extracellular Vesicles; Neural Cell Adhesion Molecule L1; Parkinson Disease
PubMed: 37449706
DOI: 10.1002/mds.29497 -
Medicine May 2015Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of... (Meta-Analysis)
Meta-Analysis Review
Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of patients with nonsmall cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. MEDLINE, EMBASE, and the Cochrane Library were searched for studies that provided data to estimate the accuracy of blood testing against tissue testing in NSCLC patients and/or those directly compared the efficacy of EGFR TKIs in EGFR mutant and wild-type patients according to sources of specimens. Sensitivity, specificity, and concordance rate were used as measures of the accuracy. Risk ratio (RR) for objective response and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were used as measures for treatment efficacy. We combined the effects by using the fixed-effects model unless there was evidence of heterogeneity, in which case a random-effects mode was used. This systematic review included 25 studies with 2605 patients. The pooled overall sensitivity, specificity, and concordance rate were 0.61, 0.90, and 0.79, respectively. Serum showed lower sensitivity (0.56 vs 0.65) but higher specificity (0.95 vs 0.85) and higher concordance (0.86 vs 0.74) than plasma. EGFR mutations (exon 19 or 21) in blood were significantly associated with objective response (RR: 4.08; 95% confidence interval [CI] 2.48-6.70), PFS (HR: 0.72; 95% CI 0.64-0.80), and OS (HR: 0.71; 95% CI 0.50-0.99). Importantly, the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma. Blood, in particular serum, is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the absence of blood positivity should not necessarily be construed with confirmed negativity.
Topics: Blood; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Genes, erbB-1; Hematologic Tests; Humans; Lung Neoplasms; Mutation; Plasma; Prognosis; Protein-Tyrosine Kinases; Sensitivity and Specificity
PubMed: 26020382
DOI: 10.1097/MD.0000000000000775