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Frontiers in Immunology 2021The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation,...
BACKGROUND
The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components , and including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy.
METHODS
We systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications.
RESULTS
Although several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages and showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway.
CONCLUSIONS
This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones crystal phagocytosis.
Topics: Animals; Calcium Oxalate; Humans; Kidney Calculi; Macrophages; Nephrolithiasis
PubMed: 34108970
DOI: 10.3389/fimmu.2021.673690 -
PloS One 2021Numerous studies have demonstrated that a variety of systemic inflammatory markers were associated with the survival of different tumors. However, the association... (Meta-Analysis)
Meta-Analysis
PURPOSE
Numerous studies have demonstrated that a variety of systemic inflammatory markers were associated with the survival of different tumors. However, the association between elevated postoperative neutrophil-lymphocyte ratio (postNLR) and long-term outcomes, including overall survival (OS), disease-free survival (DFS), in patients with solid tumors remains controversial. A systematic review was conducted to explore the association between the postNLR and long-term outcomes in solid tumors.
MATERIALS AND METHODS
Relevant literature was identified using PubMed, Embase, Web of Science, and the Cochrane Library from the initiation of the databases to October 2020. Data were extracted from included studies reporting hazard ratio (HR) and 95% confidence intervals (CI), and were pooled using generic inverse-variance and random-effects modeling. 25 studies reporting on7539 patients were included in the analysis.
RESULTS
Elevated postNLR was associated with poor OS (HR 1.87, 95% CI = 1.53-2.28; P < 0.00001), and worse DFS (HR 1.69, 95% CI = 1.28-2.22; P = 0.0002). Subgroup analyses showed that the trend of the pooled HR for most of the subgroups was not changed, and the heterogeneity of the same tumor type was not obvious. However, there was no correlation between high postNLR obtained within 7days and poor DFS (n = 3, HR 1.25, 95CI% = 0.54-2.88; P = 0.60).
CONCLUSIONS
Elevated postNLR might be a readily available and inexpensive biomarker for long-term outcomes in solid tumors. Multicenter and prospective studies are needed to explore the impact of the postNLR on the prognosis of solid tumors.
Topics: Biomarkers; Disease-Free Survival; Humans; Lymphocytes; Neoplasms; Neutrophils; Postoperative Period; Prognosis; Progression-Free Survival; Proportional Hazards Models; Survival Analysis; Treatment Outcome
PubMed: 33872342
DOI: 10.1371/journal.pone.0250091 -
Frontiers in Immunology 2024Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH...
BACKGROUND
Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied.
OBJECTIVE
This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management.
METHODS
A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria.
RESULTS
A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups.
CONCLUSION
A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.
Topics: Child; Humans; Disease Susceptibility; Homeostasis; Lymphohistiocytosis, Hemophagocytic; Immune System Diseases
PubMed: 38415256
DOI: 10.3389/fimmu.2024.1282804 -
BMJ Open Dec 2022The purpose of this study was systematically and quantitatively to assess the value of the neutrophil-to-lymphocyte ratio (NLR) for the diagnosis of neonatal sepsis by... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The purpose of this study was systematically and quantitatively to assess the value of the neutrophil-to-lymphocyte ratio (NLR) for the diagnosis of neonatal sepsis by systematic review and meta-analysis.
DESIGN
Systematic review and meta-analysis.
METHODS
Eight major databases, including The Cochrane, PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature Database and VIP Database, were systematically searched for NLR diagnoses of neonatal sepsis from inception to June 2022. Two investigators independently conducted the literature search, screening, data extraction and quality evaluation with the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Statistical analysis was performed using Review Manager V.5.3, Stata V.16.0, R (V.3.6.0) and Meta-DISC V.1.4.
RESULTS
A total of 14 studies comprising 1499 newborns were included in this meta-analysis. With a cut-off value ranging from 0.1 to 9.4, the pooled sensitivity of the NLR in the diagnosis of neonatal sepsis was 0.74 (95% CI: 0.61 to 0.83), the pooled specificity was 0.88 (95% CI: 0.73 to 0.95), the positive likelihood ratio (LR) was 6.35 (95% CI: 2.6 to 15.47), the negative likelihood ratio (LR) was 0.30 (95% CI: 0.19 to 0.46), the diagnostic OR (DOR) was 12.88 (95% CI: 4.47 to 37.08), area under the curve (AUC) was 0.87 (95% CI: 0.84 to 0.89). In the subgroup analysis of early-onset neonatal sepsis, the pooled sensitivity was 0.75 (95% CI: 0.47 to 0.91), the pooled specificity was 0.99 (95% CI: 0.88 to 1.00), the LR was 63.3 (95% CI: 5.7 to 696.8), the LR was 0.26 (95% CI: 0.10 to 0.63), the DOR was 247 (95% CI: 16 to 3785) and the AUC was 0.97 (95% CI: 0.95 to 0.98).
CONCLUSIONS
Our findings suggest that the NLR is a helpful indicator for the diagnosis of early neonatal sepsis, but it still needs to be combined with other laboratory tests and specific clinical manifestations.
Topics: Infant, Newborn; Humans; Neonatal Sepsis; Neutrophils; Biomarkers; Area Under Curve; Lymphocytes; Sensitivity and Specificity; Sepsis
PubMed: 36517090
DOI: 10.1136/bmjopen-2021-060391 -
Clinical and Applied... 2022The neutrophil-lymphocyte ratio(NLR) has been used for diagnosing venous thromboembolism (VTE). We aimed to assess the accuracy of NLR to diagnose VTE by meta-analysis.... (Meta-Analysis)
Meta-Analysis
The neutrophil-lymphocyte ratio(NLR) has been used for diagnosing venous thromboembolism (VTE). We aimed to assess the accuracy of NLR to diagnose VTE by meta-analysis. Systematic electronic searches were conducted June 2, 2021 in PubMed, Embase(Ovid), and Cochrane Library. The search did not have any language or time restriction applied. Our search strategy was based on keywords in combination with both medical subject headings (MeSH) terms and text words. The diagnostic odds ratio, summary receiver operating characteristics, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were estimated. 10 articles with 1513 VTE participants and 2593 control participants were included for quantitative synthesis. The pooled values were as follows: sensitivity = 0.68(95% CI 0.45-0.84), specificity = 0.73(95% CI 0.6-0.83), positive likelihood ratio = 2.5(95% CI 1.8-3.4), negative likelihood ratio = 0.44(95% CI 0.26-0.75), diagnostic odds ratio = 6(95% CI 3-11), and SROC = 0.76(95% CI: 0.73-0.8). NLR could be diagnostic factor for the detection of potential VTE, the accuracy thereof in the current meta-analysis exhibited moderate accuracy for diagnosing VTE. Furthermore, further large cohort studies are needed to determine optimal cut-off values of NLR.
Topics: Humans; Lymphocytes; Neutrophils; Odds Ratio; ROC Curve; Venous Thromboembolism
PubMed: 36189877
DOI: 10.1177/10760296221130061 -
Frontiers in Pharmacology 2022Diarrhea is one of the leading causes of death worldwide and is associated with immune dysfunction. The modulatory effects of Shenling Baizhu powder (SLBZS) on immune...
Diarrhea is one of the leading causes of death worldwide and is associated with immune dysfunction. The modulatory effects of Shenling Baizhu powder (SLBZS) on immune function in diarrheal disease have been validated in various animal models. However, the results of these studies have not been systematically evaluated. This study aimed to evaluate the preclinical data on SLBZS for the treatment of diarrhea from an immunological perspective. PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, VIP, and Chinese Medicine Database were searched for all animal trials on SLBZS for the treatment of diarrhea published up to April 2022. Standardized mean differences (SMD) were used as effect sizes in the meta-analysis of continuous variables, including immune organs, immune cells, and immune cytokines. Subgroup analysis was performed according to animal species and disease models. The GRADE was used to assess the quality of evidence. A total of 26 studies were included. Meta-analysis showed that compared to those in the model group, SLBZS significantly increased body weight [SMD = 1.54, 95% confidence interval (CI) (1.06, 2.02)], spleen mass [SMD = 1.42, 95% CI (0.98, 1.87)], thymus mass [SMD = 1.11, 95% CI (0.69, 1.53)], macrophage phagocytic capacity (SMD = 1.07, 95% CI [0.59, 1.54]), sIgA [SMD = 1.04, 95% CI (0.33, 1.74)], RBC-C3b-RR [SMD = 1.16, 95% CI (0.65, 1.67)], IL-2 [SMD = 1.52, 95% CI (0.89, 2.14)] and decreased diarrhea scores [SMD = -1.40, 95% CI (-2.03, -0.87)], RBC-IC-RR [SMD = -1.40, 95% CI (-1.94, -0.87)], and IL-8 [SMD = -2.80, 95% CI (-3.54, -2.07)]. Subgroup analysis showed that SLBZS regulated TNF-α, IL-1β, and IL-10 in rats and mice, and improved IL-6 and IL-10 in different diseases, with differences between subgroups ( < 0.05). Owing to heterogeneity, the reliability of the results remains to be verified. The quality of evidence was "very low". SLBZS improve diarrhea symptoms by enhancing immune function. It has curative effects with differences between different species and diseases, however, because the reporting in the original studies was too unclear to be assessed, the analysis was inconclusive. For higher quality evidences, future research should pay attention to the scientific rigor of the experimental design and the completeness of the reported results.
PubMed: 36188567
DOI: 10.3389/fphar.2022.938932 -
Clinical and Applied... 2023The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are emerging tools that can be used in the diagnosis of deep venous thrombosis (DVT).... (Meta-Analysis)
Meta-Analysis
The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are emerging tools that can be used in the diagnosis of deep venous thrombosis (DVT). This study aims to evaluate the diagnostic value of NLR and PLR for patients with DVT. Our meta-analysis included 11 eligible studies and extracted relevant diagnostic indicators. Of these studies, 4 focused on the NLR, 1 on the PLR, while 6 evaluated both. For the 10 studies on NLR, the pooled sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio were 74%, 66%, 2.16, and 0.4, respectively. The estimated diagnostic odds ratio (DOR) was 5.3, and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves was 0.74. For the 7 studies on the PLR, the pooled sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio were 0.65, 0.77, 2.89, and 0.45, respectively. The estimated DOR was 6.64, and the SROC-AUC was 0.79. Our findings showed that the NLR and PLR exhibit moderate diagnostic accuracy and may be helpful biomarkers for the diagnosis of DVT. Future prospective, well-designed studies with large sample sizes will be required to provide additional evidence to establish cutoff values and clinical value of these indicators.
Topics: Humans; Neutrophils; Lymphocytes; Blood Platelets; Biomarkers; ROC Curve; Venous Thrombosis; Retrospective Studies
PubMed: 37487186
DOI: 10.1177/10760296231187392 -
Expert Review of Molecular Diagnostics May 2021The world urgently requires surrogate markers to diagnose COVID-19 and predict its progression. The severity is not easily predicted via currently used biomarkers.... (Meta-Analysis)
Meta-Analysis
The world urgently requires surrogate markers to diagnose COVID-19 and predict its progression. The severity is not easily predicted via currently used biomarkers. Critical COVID-19 patients need to be screened for hyperinflammation to improve mortality but expensive cytokine measurement is not routinely conducted in most laboratories. The neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker in patients with various diseases. We evaluated the diagnostic and prognostic accuracy of the NLR in COVID-19 patients. We searched for relevant articles in seven databases. The quantitative analysis was conducted if at least two studies were evaluating the NLR role in COVID-19. We included 8,120 individuals, including 7,482 COVID-19 patients, from 32 articles. Patients with COVID-19 had significantly higher levels of NLR compared to negative individuals. Advanced COVID-19 stages had significantly higher levels of NLR than earlier stages. We found significantly higher levels of NLR in advanced stages compared to earlier stages of COVID-19 with good accuracy to diagnose and predict the disease outcome, especially mortality prediction. A close evaluation of critical SARS-CoV-2 patients and efficient early management are essential measures to decrease mortality. NLR could help in assessing the resource allocation in severe COVID-19 patients even in restricted settings.
Topics: Adult; Aged; COVID-19; Female; Humans; Leukocyte Count; Lymphocyte Count; Male; Middle Aged; Neutrophils; Prognosis; Sensitivity and Specificity; Severity of Illness Index
PubMed: 33840351
DOI: 10.1080/14737159.2021.1915773 -
Archives of Gynecology and Obstetrics Jan 2020Elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been identified as poor predictors of survival... (Meta-Analysis)
Meta-Analysis
PURPOSE
Elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been identified as poor predictors of survival in several malignancies. This meta-analysis was performed to quantify the effect of pretreatment NLR and PLR on the survival of patients with endometrial cancer (EC).
METHODS
This review systematically searched for relevant publications in databases of PubMed, Embase, and the Cochrane Library. Pooled hazard ratios (pHRs) with 95% confidence intervals (95% CIs) were determined and used to explore the association between inflammatory markers and overall survival (OS) and disease-free survival (DFS) in a random-effects model. Subgroup analysis, sensitivity analysis, and publication bias were also conducted in this meta-analysis.
RESULTS
Nine articles comprising 3390 patients were included. NLR higher than the cutoff was associated with a shorter OS (pHR = 2.22, 95% CI 1.77-2.78) and poorer PFS (pHR = 1.81, 95% CI 1.35-2.41). Patients with elevated PLR had high risk of decreased OS (pHR = 1.99, 95% CI = 1.51-2.61) and unfavorable PFS (pHR = 2.02, 95% CI 1.45-2.80).
CONCLUSIONS
Elevated NLR and PLR during pretreatment are biomarkers of poor prognosis in patients with EC.
Topics: Endometrial Neoplasms; Female; Humans; Lymphocytes; Neutrophils; Prognosis; Survival Analysis
PubMed: 31768743
DOI: 10.1007/s00404-019-05372-w -
Medicine Aug 2022Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed... (Meta-Analysis)
Meta-Analysis
Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs.
METHODS
A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity.
RESULTS
A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries.
CONCLUSION
Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; L-Lactate Dehydrogenase; Lymphocytes; Melanoma; Neutrophils; Prognosis
PubMed: 35960066
DOI: 10.1097/MD.0000000000029536