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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 -
Frontiers in Immunology 2023Whether neutrophil-lymphocyte ratio (NLR) is an applicative predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) remains controversial. In... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Whether neutrophil-lymphocyte ratio (NLR) is an applicative predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) remains controversial. In response to the current conflicting data, this meta-analysis was conducted to gain a comprehensive and systematic understanding of prognostic value of NLR in HCC.
METHODS
Several English databases, including PubMed, EMBASE, and the Cochrane Library, with an update date of February 25, 2023, were systematically searched. We set the inclusion criteria to include randomized controlled trial (RCT) studies that reported the prognostic value of serum NLR levels in patients with HCC receiving treatment. Both the combined ratio (OR) and the diagnosis ratio (DOR) were used to assess the prognostic performance of NLR. Additionally, we completed the risk of bias assessment by Cochrane Risk of Bias Assessment Tool.
RESULTS
This meta-analysis ultimately included 16 studies with a total of 4654 patients with HCC. The results showed that high baseline NLR was significantly associated with poor prognosis or recurrence of HCC. The sensitivity of 0.67 (95% confidence interval [CI]. 0.59-0.73); specificity of 0.723 (95% CI: 0.64-0.78) and DOR of 5.0 (95% CI: 4.0-7.0) were pooled estimated from patient-based analyses. Subsequently, the combined positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were calculated with the results of 2.4 (95% CI: 1.9-3.0) and 0.46 (95% CI: 0.39-0.56), respectively. In addition, area under the curve (AUC) of the summary receiver operating characteristic (SROC) reflecting prognostic accuracy was calculated to be 0.75 (95% CI: 0.71-0.78). The results of subgroup analysis suggested that high NLR was an effective predictive factor of poor prognosis in HCC in mainland China as well as in the northern region.
CONCLUSION
Our findings suggest that high baseline NLR is an excellent predictor of poor prognosis or relapse in patients with HCC, especially those from high-incidence East Asian populations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023440640.
Topics: Humans; Carcinoma, Hepatocellular; Neutrophils; Liver Neoplasms; Neoplasm Recurrence, Local; Lymphocytes; Prognosis
PubMed: 37809083
DOI: 10.3389/fimmu.2023.1211399 -
BMC Cardiovascular Disorders Nov 2023Neutrophil to lymphocyte ratio (NLR), as a recent inflammatory index, has been reported to be a prognostic tool in different diseases. However, implication of this ratio... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neutrophil to lymphocyte ratio (NLR), as a recent inflammatory index, has been reported to be a prognostic tool in different diseases. However, implication of this ratio in heart failure (HF) is less investigated. In this systematic review and meta-analysis, we aimed to assess the potential impact of NLR on HF clinical outcomes.
METHODS
Relevant English published records in PubMed, Scopus, Embase, and Web of Science were screened up to July 2023. Articles reporting clinical outcomes (follow-up or in-hospital mortality, readmission, HF prediction, extended hospital stay length, pulmonary vascular resistance, atrial fibrillation, renal disease and functional capacity) in HF sufferers were collected for further analysis with addition of NLR difference stratified by death/survived and HF status.
RESULTS
Thirty-six articles (n = 18231) were finally selected which reported NLR in HF sufferers (mean: 4.38, 95% confidence interval (CI): 4.02-4.73). We found 25 articles reported NLR and total mortality (either follow-up death (N = 19): 4.52 (95% CI: 4.03-5.01) or in-hospital death (N = 10): 5.33 (95% CI: 4.08-6.57)) with mean NLR of 4.74 (95% CI: 4.28-5.20). NLR was higher among deceased patients compared to survived ones (standard mean difference: 0.67 (95% CI: 0.48-0.87), P < 0.001)). NLR was found to be related with higher mortality risk (continuous variable: hazard ratio (HR): 1.12, 95% CI: 1.02-1.23, P = 0.013), categorical variable: HR: 1.77, 95% CI: 1.27-2.46, P = 0.001, T2 vs. T1: HR:1.56, 95%CI: 1.21-2.00, P = 0.001, T3 vs. T1: HR:2.49, 95%CI: 1.85-3.35, P < 0.001). Other aforementioned variables were not feasible to analyze due to presence of few studies.
CONCLUSIONS
NLR is a simple and acceptable prognostic tool for risk stratification and prioritizing high risk patients in clinical settings, especially in resource limited nations.
Topics: Humans; Neutrophils; Prognosis; Hospital Mortality; Lymphocytes; Heart Failure
PubMed: 37957565
DOI: 10.1186/s12872-023-03572-6 -
Frontiers in Immunology 2023Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint inhibitor (ICI) therapy. Nevertheless, the existing findings remain contentious.
METHODS
A comprehensive search of literature was conducted in databases including PubMed, Embase, Web of Science, and the Cochrane Library, spanning from the inception of each database to August 30, 2023 to collect studies exploring the interplay between LMR and clinical outcomes. Eligible studies were selected following predefined inclusion and exclusion criteria. Primary outcomes encompassed progression-free survival (PFS) and overall survival (OS), which were estimated using hazard ratios (HR) and corresponding 95% confidence intervals (CI).
RESULTS
Our analysis incorporated eight cohort studies, involving 815 patients. Aggregate data revealed associations between an elevated LMR at baseline and prolonged PFS (HR=0.58; 95% CI: 0.47-0.71, p<0.00001) and improved OS (HR=0.51, 95% CI: 0.33-0.79; p=0.003). Furthermore, LMR exhibited a favorable association with PFS after treatment (HR=0.48; 95% CI: 0.29-0.79; p= 0.004), while such a correlation was not evident in the OS analysis. Importantly, a high level of LMR was associated with prolonged PFS across varying sample sizes, follow-up duration, treatment combinations, line of therapy, and cut-off values.
CONCLUSION
A high pre-treatment LMR is associated with improved OS and PFS in GC patients treated with ICIs. LMR emerges as a potent biomarker for prognostic assessment in these patients, offering valuable insights for informed treatment decisions within the domain of GC immunotherapy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42021228512.
Topics: Humans; Prognosis; Monocytes; Immune Checkpoint Inhibitors; Stomach Neoplasms; Lymphocytes
PubMed: 38090560
DOI: 10.3389/fimmu.2023.1321584 -
Frontiers in Immunology 2023Gestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In addition, GDM has been linked to chronic low-grade inflammation with recent research indicating a potential immune dysregulation in pathophysiology and a disparity in regulatory T cells.
OBJECTIVE
This systematic review and meta-analysis aimed to determine whether there is an association between GDM and the level of Tregs in the peripheral blood.
METHODS
Literature searches were conducted in PubMed, Embase, and Ovid between the 7th and 14th of February 2022. The inclusion criteria were any original studies published in the English language, measuring differentiated Tregs in women with GDM compared with glucose-tolerant pregnant women. Meta-analysis was performed between comparable Treg markers. Statistical tests were used to quantify heterogeneity: , , and . Study quality was assessed using a modified version of the Newcastle-Ottawa scale.
RESULTS
The search yielded 223 results: eight studies were included in the review and seven in the meta-analysis (GDM = 228, control = 286). Analysis of Tregs across all trimesters showed significantly lower Treg numbers in women with GDM (SMD, -0.76; 95% CI, -1.37, -0.15; = 90%). This was reflected in the analysis by specific Treg markers (SMD -0.55; 95% CI, -1.04, -0.07; = 83%; third trimester, five studies). Non-significant differences were found within subgroups (differentiated by CD4FoxP3, CD4CD127, and CD4CD127FoxP3) of both analyses.
CONCLUSION
GDM is associated with lower Treg numbers in the peripheral maternal blood. In early pregnancy, there is clinical potential to use Treg levels as a predictive tool for the subsequent development of GDM. There is also a potential therapeutic intervention to prevent the development of GDM by increasing Treg populations. However, the precise mechanism by which Tregs mediate GDM remains unclear.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022309796.
Topics: Female; Humans; Pregnancy; Diabetes, Gestational; Forkhead Transcription Factors; Inflammation; Pregnancy Trimester, Third; T-Lymphocytes, Regulatory; Infant, Newborn
PubMed: 38111588
DOI: 10.3389/fimmu.2023.1226617 -
Journal of Sport and Health Science May 2024B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise...
BACKGROUND
B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, MEDLINE, Web of Science, and Embase were searched on March 8, 2023. Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions, immunoglobulin levels, salivary flow rate, or secretory immunoglobulin A secretion rate were included. Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise. Study characteristics, outcome measures, and statistically significant changes were summarized tabularly.
RESULTS
Of the 67 eligible studies, 22 applied acute exercise and 45 applied exercise training. All included outcomes revealed significant alterations over time in acute exercise and exercise training context, but only a few investigations showed significant differences compared to control conditions. Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.
CONCLUSION
B cell-related outcomes are altered by acute exercise and exercise training, but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities. Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.
Topics: Humans; Adaptive Immunity; B-Lymphocytes; Biomarkers; Exercise; Immunoglobulin A, Secretory; Saliva
PubMed: 37832643
DOI: 10.1016/j.jshs.2023.10.002 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups.
METHODS
We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias.
RESULTS
Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group.
CONCLUSIONS
Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.
Topics: Humans; Aged; Antilymphocyte Serum; Immunosuppressive Agents; Kidney Transplantation; Alemtuzumab; Antibodies; Graft Rejection; Lymphocytes; Transplant Recipients; Graft Survival
PubMed: 37774445
DOI: 10.1016/j.trre.2023.100795 -
Nutrients Mar 2024The evidence suggests that diet can modulate endogenous microRNA (miRNA) expression. Changes in miRNA expression may affect metabolic processes and consequently be... (Review)
Review
The evidence suggests that diet can modulate endogenous microRNA (miRNA) expression. Changes in miRNA expression may affect metabolic processes and consequently be involved in health status and disease development. The aim of this systematic review was to summarize the evidence of the role of diet and specific food components in the regulation of miRNA expression and discuss its implications for human health and disease development. The PubMed, Embase and Web of Science databases were searched in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for relevant studies. A total of 32 interventional and 5 observational studies performed in adults and evaluating dietary modulation of miRNA expression were included. Energy- and fat-controlled diets along with plant-based foods show substantial evidence of modulating endogenous miRNA levels. Plasma, serum and peripheral blood mononuclear cells (PBMCs) are the main sources used to measure miRNAs. A total of 108 miRNAs modulated by diet were identified. We confirmed that dietary habits are closely associated with the modulation of endogenous miRNAs. Particularly, energy content and fat intake appeared to be key factors influencing miRNA levels. Furthermore, since miRNAs are involved in the regulation of several biological processes, this modulatory process may affect health status and lead to metabolic disorders.
Topics: Adult; Humans; MicroRNAs; Leukocytes, Mononuclear; Diet
PubMed: 38542682
DOI: 10.3390/nu16060770 -
Frontiers in Immunology 2024The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple... (Review)
Review
The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of "mechanistic granularity" chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others - as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.
Topics: Humans; Autoimmune Diseases; Models, Theoretical; Multiple Sclerosis; Immunity; T-Lymphocytes
PubMed: 38550585
DOI: 10.3389/fimmu.2024.1371620 -
Frontiers in Immunology 2023The use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in immune-related adverse events (irAEs), which can cause treatment... (Meta-Analysis)
Meta-Analysis
Neutrophil to Lymphocyte ratio as a predictor for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
BACKGROUND
The use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in immune-related adverse events (irAEs), which can cause treatment discontinuation and even fatal reactions. The purpose of this study was to evaluate the usefulness of the peripheral biomarker neutrophil to lymphocyte ratio (NLR) in predicting irAEs.
METHODS
A systematic search of databases was conducted to identify studies on the predictive value of NLR for irAEs. The standardized mean difference (SMD) was used to compare continuous NLR, while crude odds ratios (ORs) were calculated for categorized NLR if adjusted ORs and 95% confidence intervals (CIs) were not provided in the original study.
RESULTS
The meta-analysis included 47 studies with a total of 11,491 cancer patients treated with ICIs. The baseline continuous NLR was significantly lower in patients with irAEs compared to those without (SMD=-1.55, 95%CI=-2.64 to -0.46, P=0.006). Similarly, categorized NLR showed that lower baseline NLR was associated with increased irAEs (OR=0.55, 95%CI=0.41-0.73, P<0.001). Subgroup analysis revealed that the OR for predicting irAEs with NLR cut-off values of 3 and 5 was 0.4 and 0.59, respectively. Interestingly, increased baseline NLR was associated with a higher incidence of immune-related liver injury (OR=2.44, 95%CI=1.23-4.84, I2 = 0%, P=0.010).
CONCLUSION
Our study suggests that lower baseline NLR is associated with a higher risk of overall irAEs. However, further studies are needed to determine the best cut-off value and explore the efficacy of NLR in predicting specific types of irAEs.
Topics: Humans; Databases, Factual; Immune Checkpoint Inhibitors; Lymphocytes; Neoplasms; Neutrophils; Odds Ratio
PubMed: 37622124
DOI: 10.3389/fimmu.2023.1234142