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BMC Cardiovascular Disorders May 2024In the current systematic review and meta-analysis, we aim to analyze the existing literature to evaluate the role of inflammatory biomarkers, including... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
In the current systematic review and meta-analysis, we aim to analyze the existing literature to evaluate the role of inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) among individuals with cardiac syndrome X (CSX) compared to healthy controls.
METHODS
We used PubMed, Web of Science, Scopus, Science Direct, and Embase to systematically search relevant publications published before April 2, 2023. We performed the meta-analysis using Stata 11.2 software (Stata Corp, College Station, TX). So, we used standardized mean difference (SMD) with a 95% confidence interval (CI) to compare the biomarker level between patients and healthy controls. The I and Cochran's Q tests were adopted to determine the heterogeneity of the included studies.
RESULTS
Overall, 29 articles with 3480 participants (1855 with CSX and 1625 healthy controls) were included in the analysis. There was a significantly higher level of NLR (SMD = 0.85, 95%CI = 0.55-1.15, I = 89.0 %), CRP (SMD = 0.69, 95%CI = 0.38 to 1.02, p < 0.0001), IL-6 (SMD = 5.70, 95%CI = 1.91 to 9.50, p = 0.003), TNF-a (SMD = 3.78, 95%CI = 0.63 to 6.92, p = 0.019), and PLR (SMD = 1.38, 95%CI = 0.50 to 2.28, p = 0.02) in the CSX group in comparison with healthy controls.
CONCLUSION
The results of this study showed that CSX leads to a significant increase in inflammatory biomarkers, including NLR, CRP, IL-6, TNF-a, and PLR.
Topics: Humans; Biomarkers; Microvascular Angina; Inflammation Mediators; Neutrophils; Female; Male; Middle Aged; Predictive Value of Tests; C-Reactive Protein; Lymphocyte Count; Interleukin-6; Aged; Platelet Count; Adult; Blood Platelets; Tumor Necrosis Factor-alpha; Lymphocytes; Prognosis; Inflammation
PubMed: 38807048
DOI: 10.1186/s12872-024-03939-3 -
The British Journal of Surgery May 2024Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this.
METHODS
A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals.
RESULTS
A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001).
CONCLUSION
The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.
Topics: Female; Humans; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Leukocyte Count; Lymphocyte Count; Neoadjuvant Therapy; Neutrophils; Predictive Value of Tests; Prognosis
PubMed: 38801441
DOI: 10.1093/bjs/znae132 -
Frontiers in Immunology 2024The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is... (Meta-Analysis)
Meta-Analysis
The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio and systemic sclerosis and its complications: a systematic review and meta-analysis.
INTRODUCTION
The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), has not been critically appraised in this patient group.
METHODS
We conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools.
RESULTS
In 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p<0.001; I = 74.5%, p<0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I = 94.1%, p<0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p<0.001; I = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I = 87.6%, p<0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p<0.001; I = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I = 94.1%, p<0.001).
DISCUSSION
Pending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cell-derived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520040.
Topics: Humans; Scleroderma, Systemic; Neutrophils; Lymphocytes; Monocytes; Blood Platelets; Lymphocyte Count; Biomarkers; Platelet Count
PubMed: 38799443
DOI: 10.3389/fimmu.2024.1395993 -
Archives of Dermatological Research May 2024Psoriasis is an immune-mediated disorder which primarily affects skin and has systemic inflammatory involvement. Neutrophil-to-lymphocyte ratio (NLR),... (Meta-Analysis)
Meta-Analysis Review
Psoriasis is an immune-mediated disorder which primarily affects skin and has systemic inflammatory involvement. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR) are novel complete blood count (CBC)-derived markers which can reflect systemic inflammation. This study aimed to systematically investigate the associations of NLR, PLR, SII, and MLR with psoriasis. This study was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A comprehensive search of Pubmed, Embase, Scopus, and Google Scholar was conducted for relevant studies. Observational studies evaluating the correlations of NLR, PLR, SII, or MLR with psoriasis were included. The primary outcomes were the associations of these inflammatory markers with the presence and severity of psoriasis. The random-effect model was applied for meta-analysis. 36 studies comprising 4794 psoriasis patients and 55,121 individuals in total were included in the meta-analysis. All inflammatory markers were significantly increased in psoriasis groups compared to healthy controls (NLR: MD = 0.59, 95% CI: 0.47-0.7; PLR: MD = 15.53, 95% CI: 8.48-22.58; SII: MD = 111.58, 95% CI: 61.49-161.68; MLR: MD = 0.034, 95% CI: 0.021-0.048; all p < 0.001). Between-group mean differences in NLR and PLR were positively correlated with the mean scores of Psoriasis Area Severity Index (NLR: p = 0.041; PLR: p = 0.021). NLR, PLR, SII, and MLR are associated with the presence of psoriasis. NLR and PLR serve as significant indicators of psoriasis severity. These novel CBC-derived markers constitute potential targets in the screening and monitoring of psoriasis.
Topics: Psoriasis; Humans; Biomarkers; Severity of Illness Index; Neutrophils; Inflammation; Lymphocytes; Blood Cell Count; Blood Platelets; Monocytes; Lymphocyte Count
PubMed: 38787437
DOI: 10.1007/s00403-024-02994-2 -
Leukemia Research Jul 2024Umbilical cord blood transplantation (UCBT) has emerged as a promising treatment option for patients with acute leukemia needing hematopoietic stem cell transplantation.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Umbilical cord blood transplantation (UCBT) has emerged as a promising treatment option for patients with acute leukemia needing hematopoietic stem cell transplantation. Both single (sUCBT) and double cord blood units (dUCBT) demonstrate potential benefits, but studies comparing their effectiveness have shown mixed results. This meta-analysis aimed to determine the comparative safety and efficacy of sUCBT versus dUCBT in acute leukemia patients.
METHODS
Electronic databases were systematically examined to identify relevant studies comparing single vs double UCBT published until November 2023. Nine studies involving 3864 acute leukemia patients undergoing UCBT were included. Outcomes analyzed were acute graft-versus-host disease (GVHD), chronic GVHD, relapse, non-relapse mortality, leukemia-free survival and overall survival. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model.
RESULTS
The risk of Grade II-IV acute GVHD (RR 1.55, 95% CI 1.19-2.03) and Grade III-IV acute GVHD (RR 1.25, 95% CI 1.07-1.46) were significantly higher with dUCBT. Relapse risk was lower with dUCBT (RR 0.57, 95% CI 0.38-0.88) while overall survival favored sUCBT (RR 1.25, 95% CI 1.06-1.46). No significant differences were observed for chronic GVHD, non-relapse mortality or leukemia-free survival.
CONCLUSION
Both single and double UCBT have potential as effective treatments for acute leukemia. The choice of treatment should consider various factors, including the risk of GVHD, relapse, and mortality. More research, especially randomized trials, is needed to provide definitive guidance on the optimal use of single and double unit UCBT in patients with acute leukemia.
Topics: Humans; Cord Blood Stem Cell Transplantation; Graft vs Host Disease; Leukemia; Leukemia, Myeloid, Acute; Acute Disease
PubMed: 38761563
DOI: 10.1016/j.leukres.2024.107517 -
British Journal of Anaesthesia Apr 2024Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic... (Review)
Review
INTRODUCTION
Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS.
METHODS
MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale.
RESULTS
Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L; P<0.01), a 4.4 g L lower albumin (95% CI 0.5-8.3 g L; P<0.01), and a 0.36×10 L lower lymphocyte count (95% CI 0.25-0.47×10 L; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly.
CONCLUSIONS
While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions.
CLINICAL TRIAL REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).
PubMed: 38688799
DOI: 10.1016/j.bja.2024.03.038 -
BMC Emergency Medicine Apr 2024The inflammatory response to burn injuries can lead to organ dysfunction that ultimately results in increased mortality and morbidity. This meta-analysis was conducted... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The inflammatory response to burn injuries can lead to organ dysfunction that ultimately results in increased mortality and morbidity. This meta-analysis was conducted to determine the efficacy of inflammatory biomarkers, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), procalcitonin (PCT), and C-reactive protein (CRP) as predictive tools of mortality among burn patients.
MATERIAL AND METHODS
The biomarker levels of survivors and non-survivors were consolidated according to guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Three main databases were searched electronically: PubMed, Web of Science, and Scopus, on December 8, 2022. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate and score the methodological quality of the included studies. The standard mean difference (SMD) with a 95% confidence interval (CI) was utilized.
RESULTS
Twenty-four studies were included in our systematic review and meta-analysis, (3636 total burn patients), of whom 2878 survived. We found that deceased burn patients had elevated levels of NLR (SMD = 0.60, 95% CI; 0.19-1.00, P < 0.001), CRP (SMD = 0.80, 95% CI; 0.02-1.58, P = 0.04), and PCT (SMD = 0.85, 95% CI; 0.45-1.24, P < 0.001), compared to survivors. However, we found no association between PLR and mortality among burn patients (SMD = 0.00, 95% CI; -0.14-0.15, P < 0.001). In addition, CRP was significantly higher in non-survivors (SMD = 0.80, 95% CI; 0.02-1.58, P =0.04). Similar results were also found about PCT (SMD = 0.85, 95% CI; 0.45-1.24, P < 0.001). When we analyzed the PCT data, collected in the first 24-48 hours, we found similar results; the PCT level was significantly higher in non-survivors in the immediate postinjury-period (SMD = 0.67, 95% CI; 0.31-1.02, P < 0.001). There was no publication bias among studies on the role of NLR in burn (Egger's test P = 0.91). The based cut-off values for NLR (13), CRP (71), and PCT (1.77) yielded sensitivities of 69.2%, 100%, and 93.33%, and specificities of 76%, 72.22%, and 72.22% respectively.
DISCUSSION/CONCLUSIONS
PCT is a marker of sepsis, therefore its elevated level is presumably associated with a higher incidence and severity of sepsis among non-survivors. In addition, NLR and CRP are promising biomarkers for predicting and guiding prevention against burn deaths in clinical settings.
Topics: Humans; Burns; Biomarkers; C-Reactive Protein; Procalcitonin; Inflammation; Neutrophils
PubMed: 38684973
DOI: 10.1186/s12873-024-00988-x -
Cancer Treatment Reviews Jun 2024Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their... (Review)
Review
BACKGROUND
Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs.
METHODS
A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria.
RESULTS
In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors.
DISCUSSION AND CONCLUSION
MSI and EBV + GCs are highly Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Tumor Microenvironment; Epstein-Barr Virus Infections; DNA Mismatch Repair; Herpesvirus 4, Human; Microsatellite Instability
PubMed: 38669788
DOI: 10.1016/j.ctrv.2024.102737 -
Medical Oncology (Northwood, London,... Apr 2024Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell... (Review)
Review
Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell (HSC) self-renewal and the generation of specialized cells. Cytokines and chemokines, two important components of the inflammatory process, also influence hematological differentiation. In this scenario, immunological dysregulation plays a pivotal role in the pathogenesis of bone marrow neoplasms. The STING pathway recognizes DNA fragments in the cell cytoplasm and triggers an immune response by type I interferons. The role of STING in cancer has not yet been established; however, both actions, as an oncogene or tumor suppressor, have been documented in other types of cancer. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42023407512) to discuss the role of STING pathway in the advancement of pathogenesis and/or prognosis for different myeloid neoplasms. In brief, scientific evidence supports investigations that primarily use cell lines from myeloid neoplasms, such as leukemia. More high-quality research and clinical trials are needed to understand the role of the STING pathway in the pathology of hematological malignancies. Finally, the STING pathway suggests being a promising therapeutic molecular target, particularly when combined with current drug therapies.
Topics: Humans; Hematologic Neoplasms; Membrane Proteins; Myeloproliferative Disorders; Signal Transduction
PubMed: 38656461
DOI: 10.1007/s12032-024-02376-8 -
Journal of Nanobiotechnology Apr 2024Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on... (Review)
Review
Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.
Topics: Osteogenesis; Endothelial Cells; Bone Regeneration; Osteoclasts; Nanostructures; Cell Differentiation
PubMed: 38627717
DOI: 10.1186/s12951-024-02442-3