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Medicina (Kaunas, Lithuania) Aug 2022Background and Objectives: Advanced non-small-cell lung cancer (NSCLC) has led to a high number of mortalities. Immunotherapy, as a first-line treatment in advanced... (Meta-Analysis)
Meta-Analysis Review
Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Markers for Advanced Non-Small-Cell Lung Cancer Treated with Immunotherapy: A Systematic Review and Meta-Analysis.
Background and Objectives: Advanced non-small-cell lung cancer (NSCLC) has led to a high number of mortalities. Immunotherapy, as a first-line treatment in advanced NSCLC, currently has no clarity regarding its prognostic markers to assess the treatment outcome. This systematic review aimed to evaluate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in advanced NSCLC patients treated with immunotherapy. Materials and Methods: This systematic review was conducted using the PRISMA guidelines, starting from screening for relevant studies from several databases. Each included cohort study was further assessed by using the Newcastle−Ottawa Quality Assessment Scale, and the available data were extracted for qualitative and quantitative synthesis in pooled and subgroup analysis. Results: A total of 1719 patients were included in this meta-analysis. Hazard ratio (HR) outcomes for progression-free survival (PFS) and overall survival (OS) for NLR and PLR showed significant results, supporting NLR and PLR as prognostic markers (NLR: HR PFS 2.21 [95% CI: 1.50−3.24; p < 0.0001] and HR OS 2.68 [95% CI: 2.24−3.6; p < 0.0001]; PLR: HR PFS 1.57 [95% CI: 1.33−1.84; p < 0.00001] and HR OS 2.14 [95% CI: 1.72−2.67; p < 0.00001]). Subgroup analysis with a cut-off value of 5 for NLR and 200 for PLR also demonstrated notable outcomes. Higher NLR and PLR levels are associated with poor prognostic. Conclusions: There is considerable evidence regarding both markers as prognostic markers in NSCLC patients treated with immunotherapy. However, further studies with more homogeneous baseline characteristics are required to confirm these findings.
Topics: Carcinoma, Non-Small-Cell Lung; Cohort Studies; Humans; Immunotherapy; Lung Neoplasms; Lymphocytes; Neutrophils; Prognosis; Retrospective Studies
PubMed: 36013536
DOI: 10.3390/medicina58081069 -
Journal of Diabetes Research 2023Glycated hemoglobin (HbA1c) is a commonly used clinical marker to monitor the control of type 2 diabetes mellitus patients (T2DM). However, it is unable to identify the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glycated hemoglobin (HbA1c) is a commonly used clinical marker to monitor the control of type 2 diabetes mellitus patients (T2DM). However, it is unable to identify the ongoing inflammatory changes in the body. These factors could be easily identified and monitored by the neutrophil-to-lymphocyte ratio (NLR). Therefore, this study is aimed at investigating the relationship between NLR and glycemic control in T2DM.
METHOD
A comprehensive search of eligible studies was performed in various databases published until July 2021. A random effect model was used to estimate the standardized mean difference (SMD). A metaregression, subgroup, and sensitivity analysis were conducted to search for potential sources of heterogeneity.
RESULT
A total of 13 studies were included in this study. Accordingly, the SMD of the NLR values between the poor and good glycemic control groups was 0.79 (95% CI, 0.46-1.12). Our study also showed that high NLR was significantly associated with poor glycemic control in T2DM patients (OR = 1.50, 95% CI: 1.30-1.93).
CONCLUSION
The results of this study suggest an association between high NLR values and an elevated HbA1C in T2DM patients. Therefore, NLR should be considered a marker of glycemic control in addition to HbA1c in T2DM patients.
Topics: Humans; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Neutrophils; Lymphocytes
PubMed: 37305430
DOI: 10.1155/2023/3117396 -
Frontiers in Immunology 2022Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this... (Review)
Review
Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this malignant disease. More and more attention has been paid to the roles of macrophages in the TME. This article briefly summarizes the origin of macrophages, the mutual regulation between anti-tumoral immunity and pro-tumoral statuses derived from macrophage polarization, and the therapeutic opportunities targeting alternately activated macrophages (AAM)-type macrophage polarization. Among them, cellular components including T cells, as well as acellular components represented by IL-4 and IL-13 are key regulators driving the polarization of AAM macrophages. Novel treatments targeting macrophage-associated mechanisms are mainly divided into small molecule inhibitors, monoclonal antibodies, and other therapies to re-acclimate AMM macrophages. Finally, we paid special attention to an immunosuppressive subgroup of macrophages with T cell immunoglobulin and mucin domain-3 (TIM-3) expression. Based on cellular interactions with cancer cells, TIM3+ macrophages facilitate the proliferation and progression of cancer cells, yet this process exposes targets blocking the ligand-receptor recognition. To sum up, this is a systematic review on the mechanism of tumor-associated macrophages (TAM) polarization, therapeutic strategies and the biological functions of Tim-3 positive macrophages that aims to provide new insights into the pathogenesis and treatment of lung cancer.
Topics: Humans; Hepatitis A Virus Cellular Receptor 2; Lung Neoplasms; Macrophages; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 36439090
DOI: 10.3389/fimmu.2022.1007812 -
The Journal of Investigative Dermatology Nov 2022Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to... (Meta-Analysis)
Meta-Analysis
Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.
Topics: Rats; Animals; Burns; Neutrophils; Macrophages; Anti-Bacterial Agents; Inflammation Mediators
PubMed: 35623415
DOI: 10.1016/j.jid.2022.05.004 -
BMC Women's Health Nov 2023The purpose of this systematic review and meta-analysis was to compile existing evidence on the significance of the NLR in predicting endometriosis in order to aid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this systematic review and meta-analysis was to compile existing evidence on the significance of the NLR in predicting endometriosis in order to aid clinical decision-making and outcomes.
METHODS
We searched ProQuest, Web of Science, and PubMed for related studies published before January 2, 2023. Standardized mean difference (SMD) with a 95% confidence interval (CI) was reported for each outcome. Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used Newcastle-Ottawa Scale (NOS) for quality assessment.
RESULTS
Overall, 18 article with were included in the analysis. A random-effect model revealed that patients with endometriosis had elevated levels of NLR compared to healthy controls (SMD = 0.79, 95% CI = 0.33 to 1.25, P < 0.001). Patients with endometriosis had elevated levels of NLR compared to those with other benign tumors (SMD = 0.85, 95% CI = 0.17 to 1.53, P = 0.014). In addition, NLR level of patients with stage III and IV endometriosis was not different from that of patients with stage I and II endometrioma (SMD = 0.30, 95% CI = -0.14 to 0.74, P = 0.18). However, NLR level was not different between endometriosis patients with and without peritoneal lesions (SMD = -0.12, 95% CI = -0.34to 0.10, P = 0.28), between patients with and without endometrioma (SMD = 0.20, 95% CI = -0.15 to 0.55, P = 0.26) and between endometriosis patients with and without deep lesions (SMD = 0.04, 95% CI = -0.20 to 0.28, P = 0.72). The pooled sensitivity of NLR was 0.67 (95% CI = 0.60-0.73), and the pooled specificity was 0.68 (95% CI, 0.62-0.73).
CONCLUSIONS
NLR might be utilized in clinics as a possible predictor to help clinicians diagnose endometriosis in affected women.
Topics: Humans; Female; Endometriosis; Neutrophils; Lymphocytes; Peritoneal Diseases
PubMed: 37936116
DOI: 10.1186/s12905-023-02692-7 -
Experimental & Molecular Medicine Mar 2024Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections,... (Review)
Review
Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Macrophages
PubMed: 38448692
DOI: 10.1038/s12276-024-01182-6 -
Mediators of Inflammation 2022This study was conducted to summarize the results of studies investigating the role of neutrophil to lymphocyte ratio (NLR) in epilepsy. The search was conducted on... (Review)
Review
This study was conducted to summarize the results of studies investigating the role of neutrophil to lymphocyte ratio (NLR) in epilepsy. The search was conducted on PubMed, Scopus, and Web of Science up to December 25, 2021. Finally, a total of seven studies were included in the review. The NLR in patients who were in the acute phase was higher than that of healthy. NLR in the patients who were in either acute or subacute phase was higher than in healthy controls. A significant difference in NLR levels between the acute and subacute phases was also noted. Epilepsy is one of the most important neurological diseases in the world, and millions of people around the world suffer from it, and a cheap and fast biomarker is needed for it. The interesting thing is that inflammation plays a role in epilepsy, and elevated NLR value can be a good biomarker of inflammation and, as a result, for epilepsy.
Topics: Biomarkers; Epilepsy; Humans; Inflammation; Lymphocytes; Neutrophils
PubMed: 36081651
DOI: 10.1155/2022/4973996 -
International Journal of Molecular... Aug 2022Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to... (Review)
Review
Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.
Topics: Gene Expression Regulation; Humans; Macrophages; MicroRNAs; Multiple Organ Failure; Sepsis
PubMed: 36012630
DOI: 10.3390/ijms23169354 -
Clinical and Experimental Dental... Aug 2022This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces. (Review)
Review
OBJECTIVES
This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces.
MATERIAL AND METHODS
An electronic search for literature was conducted on PubMed, Embase, Scopus, and Web of Science and a total of 14 studies were included. Neutrophil responses were assessed based on adhesion, cell number, surface coverage, cell structure, cytokine secretion, reactive oxygen species (ROS) production, neutrophil activation, receptor expression, and neutrophil extracellular traps (NETs) release. The method of assessing the risk of bias was done using the toxicological data reliability assessment tool (TOXRTOOL).
RESULTS
Ten studies have identified a significant increase in neutrophil functions, such as surface coverage, cell adhesion, ROS production, and NETs released when interacting with rough titanium surfaces. Moreover, neutrophil interaction with rough-hydrophilic surfaces seems to produce less proinflammatory cytokines and ROS when compared to naive smooth and rough titanium surfaces. Regarding membrane receptor expression, two studies have reported that the FcγIII receptor (CD16) is responsible for initial neutrophil adhesion to hydrophilic titanium surfaces. Only one study compared neutrophil interaction with titanium alloy and zirconia toughened alumina surfaces and reported no significant differences in neutrophil cell count, activation, receptor expression, and death.
CONCLUSIONS
There are not enough studies to conclude neutrophil interactions with titanium and zirconia surfaces. However, different topographic modifications such as roughness and hydrophilicity might influence neutrophil interactions with titanium implant surfaces.
Topics: Dental Implants; Neutrophils; Reactive Oxygen Species; Reproducibility of Results; Surface Properties; Titanium; Zirconium
PubMed: 35535662
DOI: 10.1002/cre2.582 -
Frontiers in Immunology 2023Ageing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Ageing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations, a plethora of data exist and the power of scientific conclusions can vary substantially. This meta-analysis by information content (MAIC) and systematic literature review (SLR) aims to determine overall changes in macrophage gene and protein expression, as well as function, with age.
METHODS
PubMed was utilized to collate peer-reviewed literature relating to macrophage ageing. Primary studies comparing macrophages in at least two age groups were included. Data pertaining to gene or protein expression alongside method used were extracted for MAIC analysis. For SLR analysis, data included all macrophage-specific changes with age, as well as species, ontogeny and age of groups assessed.
RESULTS
A total of 240 studies were included; 122 of which qualified for MAIC. The majority of papers focussed on changes in macrophage count/infiltration as a function of age, followed by gene and protein expression. The MAIC found iNOS and TNF to be the most commonly investigated entities, with 328 genes and 175 proteins showing consistent dysregulation with age across the literature. Overall findings indicate that cytokine secretion and phagocytosis are reduced and reactive oxygen species production is increased in the ageing macrophage.
DISCUSSION
Collectively, our analysis identifies critical regulators in macrophage ageing that are consistently dysregulated, highlighting a plethora of targets for further investigation. Consistent functional changes with age found here can be used to confirm an ageing macrophage phenotype in specific studies and experimental models.
Topics: Macrophages; Phagocytosis
PubMed: 37520567
DOI: 10.3389/fimmu.2023.1222308