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Medicina (Kaunas, Lithuania) Sep 2022Background and objective: Among the broad variety of chemokines, monocyte chemoattractant protein-1 (MCP-1) is considered to be one of the most important chemokines.... (Meta-Analysis)
Meta-Analysis Review
Background and objective: Among the broad variety of chemokines, monocyte chemoattractant protein-1 (MCP-1) is considered to be one of the most important chemokines. Among others, MCP-1 activates monocytes and other immune cells highly involved in inflammation. In the present systematic review and meta-analysis, we evaluated the relationship between serum/plasma MCP-1 levels and the risk of obstructive sleep apnea (OSA) in adults as a disease related to inflammation. Materials and methods: Four databases were systematically investigated until 12 July 2022. We used the Review Manager 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) to extract and calculate the standardized mean difference (SMD) and its 95% confidence interval (CI) of plasma/serum levels of MCP-1 between adults with and without OSA. Results: Eight articles including eleven studies in adults were entered into the meta-analysis. The serum/plasma MCP-1 levels in adults with OSA were higher than that in the controls (SMD = 0.81; p = 0.0007) and as well as for adults with severe OSA compared to those with mild and moderate OSA (SMD = 0.42; p < 0.0001). The subgroup analysis showed that ethnicity was an effective factor in the pooled analysis of blood MCP-1 levels in adults with OSA compared to the controls (Asians: (p < 0.0001), mixed ethnicity: (p = 0.04), and Caucasians: (p = 0.89)). The meta-regression showed increasing serum/plasma MCP-1 levels in adults with OSA versus the controls, publication year, age of controls, body mass index (BMI) of controls, and sample size reduced, and also BMI and the apnea−hypopnea index of adults with OSA increased. Conclusions: The meta-analysis showed that compared to the controls, serum/plasma levels of MCP-1 in adults with OSA were significantly more, as well as adults with severe OSA having more serum/plasma MCP-1 levels compared to the adults with mild to moderate OSA. Therefore, MCP-1 can be used as a diagnostic and therapeutic factor in adults with OSA.
Topics: Adult; Chemokine CCL2; Humans; Inflammation; Monocytes; Sleep Apnea, Obstructive
PubMed: 36143943
DOI: 10.3390/medicina58091266 -
Modern Pathology : An Official Journal... Aug 2020Macrophage polarization is relevant for tumor biology. M2 polarized macrophages favor tumor growth and survival, while M1 macrophages support tumor destruction and... (Meta-Analysis)
Meta-Analysis
Macrophage polarization is relevant for tumor biology. M2 polarized macrophages favor tumor growth and survival, while M1 macrophages support tumor destruction and antigen presentation. Markers identifying M1/M2 polarization are a subject of debate. We conducted a systematic review and meta-analysis to investigate the association of proposed macrophage markers with prognosis across epithelial tumors and melanoma. The Medline search engine was used and 195 articles were recovered for full review. Only articles which measured markers using immunohistochemistry or immunofluorescence and had overall survival (OS) as the primary endpoint were included. One hundred and thirteen articles were finally accepted for analysis. CD68 was associated with worse survival across tumors (hazard ratio (HR) = 1.24, 95% CI = 1.11-1.37). Tumor anatomical location influenced this association. Colorectal tumors showed an inverse association between CD68 and OS in contrast to the rest of cancer types (HR = 0.56 vs. 1.34). The approach taken to measure CD68 had an impact on prognosis; when macrophages were measured at the tumor invasion front prognosis was more favorable than when they were measured intratumorally (HR = 0.94 vs. 1.4). CD163, CD204, and CD206 showed a robust association with worse OS (HR = 1.63, 1.95, 1.65, respectively). Tumors arising in the lung and the liver showed a weaker association between CD163 and OS as compared with other locations (β = -0.5401 for the lung and -0.5940 for the liver compared with other anatomical locations). The counting strategy also had an impact on CD163 association with OS, with hot-spot counting having higher HRs compared with averaging macrophage counts across spots or absolute cell counting (β = -0.4678). In conclusion, proposed M2 markers are associated with worse survival across epithelial tumors and melanoma. The anatomical origin of tumors influences this association. The compartment where the macrophages were scored and counting strategy influenced the association with OS of CD68 and CD163, respectively.
Topics: Biomarkers, Tumor; Humans; Macrophages; Melanoma; Neoplasms, Glandular and Epithelial; Prognosis
PubMed: 32291396
DOI: 10.1038/s41379-020-0534-z -
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 -
The Journal of Infection Oct 2020Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment.
METHODS
We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI).
RESULTS
845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients.
CONCLUSIONS
COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.
Topics: Betacoronavirus; C-Reactive Protein; COVID-19; Coronavirus Infections; Diabetes Mellitus; Female; Humans; Hypertension; L-Lactate Dehydrogenase; Lung Diseases; Male; Middle East Respiratory Syndrome Coronavirus; Neutrophils; Pandemics; Pneumonia, Viral; Risk Factors; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Sex Factors
PubMed: 32634459
DOI: 10.1016/j.jinf.2020.07.002 -
Frontiers in Immunology 2022Tuberculosis (TB), caused by respiratory infection with , remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille... (Review)
Review
Tuberculosis (TB), caused by respiratory infection with , remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille Calmette-Guérin has variable efficacy and often provides poor protection against adult pulmonary TB, the transmissible form of the disease. Thus, the lack of an optimal TB vaccine is one of the key barriers to TB control. Recently, the development of highly efficacious COVID-19 vaccines within one year accelerated the vaccine development process in human use, with the notable example of mRNA vaccines and adenovirus-vectored vaccines, and increased the public acceptance of the concept of the controlled human challenge model. In the TB vaccine field, recent progress also facilitated the deployment of an effective TB vaccine. In this review, we provide an update on the current virus-vectored TB vaccine pipeline and summarize the latest findings that might facilitate TB vaccine development. In detail, on the one hand, we provide a systematic literature review of the virus-vectored TB vaccines are in clinical trials, and other promising candidate vaccines at an earlier stage of development are being evaluated in preclinical animal models. These research sharply increase the likelihood of finding a more effective TB vaccine in the near future. On the other hand, we provide an update on the latest tools and concept that facilitating TB vaccine research development. We propose that a pre-requisite for successful development may be a better understanding of both the lung-resident memory T cell-mediated mucosal immunity and the trained immunity of phagocytic cells. Such knowledge could reveal novel targets and result in the innovative vaccine designs that may be needed for a quantum leap forward in vaccine efficacy. We also summarized the research on controlled human infection and ultra-low-dose aerosol infection murine models, which may provide more realistic assessments of vaccine utility at earlier stages. In addition, we believe that the success in the ongoing efforts to identify correlates of protection would be a game-changer for streamlining the triage of multiple next-generation TB vaccine candidates. Thus, with more advanced knowledge of TB vaccine research, we remain hopeful that a more effective TB vaccine will eventually be developed in the near future.
Topics: Animals; COVID-19; COVID-19 Vaccines; Humans; Mice; Tuberculosis; Tuberculosis Vaccines; Vaccine Development
PubMed: 35812383
DOI: 10.3389/fimmu.2022.895020 -
BioMed Research International 2022The neutrophil to lymphocyte ratio (NLR) reflects a dynamic relationship between the innate (neutrophils) and adaptive (lymphocytes) cellular immune response. This... (Meta-Analysis)
Meta-Analysis Review
The neutrophil to lymphocyte ratio (NLR) reflects a dynamic relationship between the innate (neutrophils) and adaptive (lymphocytes) cellular immune response. This systematic review and meta-analysis was conducted to critically evaluate the literature regarding the use of the NLR as a reliable means to detect several ocular disorders. Our study was registered with the PROSPERO (ID: CRD42022314850). Three databases, including PubMed, Embase, Scopus, and the Web of Science, were searched on September 9, 2022, with no restrictions on the article's language. Finally, 32 articles were recognized as eligible for our meta-analysis. We found that patients with eye diseases had significantly elevated levels of NLR in comparison to healthy controls (SMD =0.53, 95% CI =0.35-0.71, < 0.001). In subgroup analysis, patients with keratoconus (SMD =0.69; 95% CI =0.33-1.05, < 0.001), glaucoma (SMD =0.56, 95% CI =0.25-0.87, < 0.001), pterygium (SMD =0.14; 95% CI =0.01-0.26, < 0.001), and idiopathic epiretinal membrane (SMD =0.14; 95% CI =0.01-0.26, < 0.001) had higher levels of NLR compared to healthy controls. However, NLR levels of patients with dry eye disease were similar to healthy controls (SMD =0.32, 95% CI = -0.49-1.13, = 0.435). It can be said that NLR is a valuable marker of systemic inflammation, which is significantly increased in many eye disorders, suggesting that inflammation plays a key role in the pathophysiology of these diseases.
Topics: Humans; Neutrophils; Lymphocytes; Biomarkers; Eye Diseases; Inflammation; Lymphocyte Count
PubMed: 36281463
DOI: 10.1155/2022/5744008 -
Allergy, Asthma, and Clinical... Aug 2023Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most...
BACKGROUND
Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken.
OBJECTIVES
To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness.
METHODS
For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction.
RESULTS
Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases.
CONCLUSION
Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).
PubMed: 37559153
DOI: 10.1186/s13223-023-00831-1 -
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 -
Scientific Reports Jul 2022The neutrophil-to-lymphocyte ratio (NLR) is used as biomarker in malignant diseases showing significant association with poor oncological outcomes. The main research... (Meta-Analysis)
Meta-Analysis
The neutrophil-to-lymphocyte ratio (NLR) is used as biomarker in malignant diseases showing significant association with poor oncological outcomes. The main research question of the present study was whether NLR has also prognostic value in cholangiocarcinoma patients (CCA). A systematic review was carried out to identify studies related to NLR and clinical outcomes in CCA evaluating the literature from 01/2000 to 09/2021. A random-effects model, pooled hazard ratios (HR) and 95% confidence interval (CI) were used to investigate the statistical association between NLR and overall survival (OS) as well as disease-free survival (DFS). Subgroup analyses, evaluation of sensitivity and risk of bias were further carried out. 32 studies comprising 8572 patients were eligible for this systematic review and meta-analysis. The pooled outcomes revealed that high NLR prior to treatment is prognostic for poor OS (HR 1.28, 95% CI 1.18-1.38, p < 0.01) and DFS (HR 1.39, 95% CI 1.17-1.66, p < 0.01) with meaningful HR values. Subgroup analysis revealed that this association is not significantly affected by the treatment modality (surgical vs. non-surgical), NLR cut-off values, age and sample size of the included studies. Given the likelihood of NLR to be prognostic for reduced OS and DFS, pre-treatment NLR might serve as a useful biomarker for poor prognosis in patients with CCA and therefore facilitate clinical management.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Lymphocytes; Neutrophils; Prognosis
PubMed: 35879385
DOI: 10.1038/s41598-022-16727-w -
Mediators of Inflammation 2022In this study, we conducted a systematic review and meta-analysis regarding the role of the neutrophil to lymphocyte ratio (NLR) in Guillain Barré syndrome (GBS). The... (Meta-Analysis)
Meta-Analysis Review
In this study, we conducted a systematic review and meta-analysis regarding the role of the neutrophil to lymphocyte ratio (NLR) in Guillain Barré syndrome (GBS). The most recent update to the search was on July 18, 2022, through the databases of Web of Science, PubMed, Embase, and Scopus. The Newcastle-Ottawa scale was used for quality assessment of included studies. Finally, 14 studies were included in the review, and among them, ten studies were included in the meta-analysis. Our results showed that NLR levels were significantly increased in the patients with GBS compared with healthy controls (SMD = 1.05; 95%CI = 0.59 to 1.50, < 0.001). After treatment, NLR levels were decreased to the extent that they became similar to healthy controls (SMD = -0.03, 95%CI = -0.29 to 0.22, = 0.204). Moreover, NLR was a stable predictor of outcome or response to treatment in such patients (SMD = 1.01, 95%CI = 0.65 to 1.37, < 0.001); the higher the NLR, the worse the outcome. In addition, patients who underwent mechanical ventilation had higher levels of NLR compared to those who did not (SMD = 0.93, 95%CI = 0.05 to 1.82, = 0.03). However, NLR levels were not different among distinct GBS subtypes, so it could not distinguish among them. In conclusion, our analysis indicates that the NLR levels are highly elevated in patients with GBS. Therefore, the NLR has the potential to be used as a biomarker to inform diagnosis, prognosis, or treatment responses in GBS, and future studies are warranted.
Topics: Biomarkers; Guillain-Barre Syndrome; Humans; Lymphocytes; Neutrophils; Prognosis
PubMed: 36133742
DOI: 10.1155/2022/3390831