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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 -
Andrology Jul 2024One of the most intriguing aspects of male reproductive physiology is the ability of the epididymis to prevent the mounting of immune responses against the onslaught of... (Review)
Review
INTRODUCTION
One of the most intriguing aspects of male reproductive physiology is the ability of the epididymis to prevent the mounting of immune responses against the onslaught of foreign antigens carried by spermatozoa while initiating very efficient immune responses versus stressors. Epithelial clear cells are strategically positioned to work in a concerted manner with region-specific heterogeneous subsets of mononuclear phagocytes to survey the epididymal barrier and regulate the balance between inflammation and immune tolerance in the post-testicular environment.
OBJECTIVE
This review aims to describe how clear cells communicate with mononuclear phagocytes to contribute to the unique immune environment in which sperm mature and are stored in the epididymis.
MATERIALS/METHODS
A comprehensive systematic review was performed. PubMed was searched for articles specific to clear cells, mononuclear phagocytes, and epididymis. Articles that did not specifically address the target material were excluded.
RESULTS
In this review, we discuss the unexpected roles of clear cells, including the transfer of new proteins to spermatozoa via extracellular vesicles and nanotubes as they transit along the epididymal tubule; and we summarize the immune phenotype, morphology, and antigen capturing, processing, and presenting abilities of mononuclear phagocytes. Moreover, we present the current knowledge of immunoregulatory mechanisms by which clear cells and mononuclear phagocytes may contribute to the immune-privileged environment optimal for sperm maturation and storage.
DISCUSSION AND CONCLUSION
Notably, we provide an in-depth characterization of clear cell-mononuclear phagocyte communication networks in the steady-state epididymis and in the presence of injury. This review highlights crucial concepts of mucosal immunology and cellcell interactions, all of which are critical but understudied facets of human male reproductive health.
Topics: Male; Epididymis; Humans; Epithelial Cells; Phagocytes; Animals; Spermatozoa; Immune Tolerance
PubMed: 37572347
DOI: 10.1111/andr.13509 -
American Journal of Surgery Mar 2024The established association between the inflammatory marker, neutrophil-lymphocyte ratio (NLR), and both long-term surgical prognosis and short-term postoperative... (Meta-Analysis)
Meta-Analysis Review
The significance of preoperative neutrophil-to-lymphocyte ratio in predicting short-term complications and survival benefits of pancreaticoduodenectomy: A systematic review and meta-analysis.
BACKGROUND
The established association between the inflammatory marker, neutrophil-lymphocyte ratio (NLR), and both long-term surgical prognosis and short-term postoperative complications is well-recognized. However, its prognostic value in pancreaticoduodenectomy (PD) is yet to be ascertained. This meta-analysis investigates the prognostic relevance of preoperative NLR in PD patients.
METHOD
We systematically searched electronic databases to identify studies exploring the relationship between pre-treatment blood NLR levels and overall survival (OS), disease-free survival (DFS), and immediate postoperative complications in PD patients. Statistical evaluations, using RevMan 5.4 and Stata 12, focused on hazard ratios (HRs) and risk ratios (RRs). Additionally, subgroup analyses, publication bias tests, and sensitivity analyses were performed.
RESULT
Our analysis encompassed 18 retrospective studies, with NLR cutoff values ranging from 2 to 3.8. The meta-analysis revealed that PD patients with elevated NLR had diminished OS and DFS, evidenced by an HR of 1.35 (95% CI: 1.11-1.64, p = 0.003) and 1.62 (95% CI: 1.15-2.27, p = 0.005), respectively. Moreover, NLR emerged as an independent determinant of immediate postoperative complications, indicated by an OR of 1.91 (95% CI: 1.01-3.59, p = 0.013) and an HR of 2.15 (95% CI: 1.23-3.73, p < 0.01).
CONCLUSION
NLR serves as a significant prognostic indicator for both OS and DFS following PD and is a reliable predictor of postoperative complications. Preoperative Neutrophil-to-Lymphocyte Ratio (NLR) is a significant prognostic indicator for overall survival (OS) and disease-free survival (DFS) in patients undergoing pancreaticoduodenectomy (PD).
Topics: Humans; Neutrophils; Lymphocyte Count; Pancreaticoduodenectomy; Retrospective Studies; Lymphocytes; Prognosis; Postoperative Complications
PubMed: 38101977
DOI: 10.1016/j.amjsurg.2023.11.030 -
Cardiology in the Young Aug 2023Kawasaki disease is a vasculitis that can lead to cardiac complications, including coronary artery disease and cardiogenic shock. Various scoring systems have been... (Review)
Review
BACKGROUND
Kawasaki disease is a vasculitis that can lead to cardiac complications, including coronary artery disease and cardiogenic shock. Various scoring systems have been developed to determine those that will be refractory to routine intravenous immunoglobulin therapy or develop coronary artery disease. The objective of this study was to determine if the neutrophil-lymphocyte ratio could predict refractory disease and coronary artery lesions in patients with Kawasaki disease.
METHODS
A systematic review of the literature was performed to identify manuscripts describing comparisons of neutrophil-lymphocyte ratio between those who had refractory disease and those who did not, and between those who developed coronary artery lesions and those who did not. Mean difference was compared between groups. Areas under the curve were utilised to determine the pooled area under the curve.
RESULTS
12 studies with 5593 patients were included in the final analyses of neutrophil-lymphocyte ratio for the prediction of refractory disease. Neutrophil-lymphocyte ratio before therapy was higher in refractory disease with a mean difference of 2.55 (p < 0.01) and pooled area under the curve of 0.724. Neutrophil-lymphocyte ratio after therapy was higher in refractory disease with a mean difference of 1.42 (p < 0.01) and pooled area under the curve for of 0.803. Five studies with 1690 patients were included in the final analyses of neutrophil-lymphocyte ratio for the prediction of coronary artery lesions. Neutrophil-lymphocyte ratio before therapy was higher in coronary artery lesions with a mean difference of 0.65 (p < 0.01).
CONCLUSION
The use of neutrophil-lymphocyte ratio may help physicians in the identification of patients at risk of refractory disease and coronary artery lesions in patients with Kawasaki disease.
Topics: Humans; Infant; Coronary Artery Disease; Immunoglobulins, Intravenous; Lymphocytes; Mucocutaneous Lymph Node Syndrome; Neutrophils; Retrospective Studies
PubMed: 37012661
DOI: 10.1017/S1047951123000653 -
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 -
International Immunopharmacology May 2024The Neutrophil-to-lymphocyte ratio (NLR) holds relevance in cancer immunotherapy outcomes, yet its validation remains limited. Thus, we conducted an umbrella review to...
BACKGROUND
The Neutrophil-to-lymphocyte ratio (NLR) holds relevance in cancer immunotherapy outcomes, yet its validation remains limited. Thus, we conducted an umbrella review to comprehensively assess the association between pretreatment NLR and immunotherapy outcomes, along with evaluating their credibility and strength.
METHODS
Electronic databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane, were systematically searched for eligible systematic reviews and meta-analyses. Quality assessment and evidence grading utilized AMSTAR, GRADE, and additional classification criteria, following PRISMA and PRIOR guidelines.
RESULTS
Thirty unique meta-analyses were included, with 24 associations (80%) exhibiting statistical significance. Notably, associations between pretreatment NLR and the prognosis of renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer garnered highly suggestive or convincing evidence grading.
CONCLUSIONS
Elevated pretreatment NLR correlates with poor outcomes in cancer immunotherapy, suggesting its potential as a biomarker for identifying appropriate treatment populations and predicting clinical outcomes. Nevertheless, further validation through prospective cohort studies is warranted.
Topics: Humans; Immunotherapy; Lymphocytes; Meta-Analysis as Topic; Neoplasms; Neutrophils; Prognosis; Treatment Outcome
PubMed: 38579566
DOI: 10.1016/j.intimp.2024.111936 -
Ratios from full blood count as markers for TB diagnosis, treatment, prognosis: a systematic review.The International Journal of... Nov 2023The monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte (NLR) ratio are calculated from routine full blood counts. The aim of this study was to systematically...
The monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte (NLR) ratio are calculated from routine full blood counts. The aim of this study was to systematically review MLR and NLR as biomarkers for diagnosis, treatment response monitoring and prognostic biomarker for TB infection or disease. A systematic literature search was conducted in Medline, Embase and the Cochrane Library on 12 January 2022. The following search terms were used: tuberculosis AND (monocyte OR neutrophils), AND lymphocytes AND (diagnostic OR prognostic OR treatment). A total of 2,314 studies were identified, of which 41, covering 11,952 individuals, were included in the final analysis. Studies enrolled a median of 154 individuals (IQR 108-301). Increased MLR and NLR were associated with TB disease when compared to healthy controls and individuals with TB infection. MLR was shown to be prognostic for progression to TB disease and to decrease in response to TB treatment. The cut-offs determined in the studies were highly variable for MLR and NLR, making it impractical to conduct a meta-analysis of sensitivity and specificity. Higher MLR and NLR are associated with TB disease and could be used as easy-to-obtain, low-cost additional diagnostic biomarkers. Further studies investigating these biomarkers are needed.
Topics: Humans; Biomarkers; Lymphocytes; Monocytes; Neutrophils; Prognosis; Retrospective Studies; Tuberculosis
PubMed: 37880883
DOI: 10.5588/ijtld.22.0598 -
Journal of Cardiovascular Translational... Apr 2024Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute... (Meta-Analysis)
Meta-Analysis
Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute coronary syndrome (ACS) patients. We conducted a systematic review to examine neutrophil-enriched biomarkers and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS. We identified twenty-seven studies including 17,831 patients with ACS. The most studied biomarkers were neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). Meta-analyses showed that elevated NGAL was associated with higher MACE rates (unadjusted risk ratio (RR) 1.52, 95% CI 1.12-2.06, p = 0.006) as were elevated MPO levels (unadjusted RR 1.61, 95% CI 1.22-2.13, p = 0.01). There was limited data suggesting that increased levels of calprotectin, proteinase-3 and double-stranded DNA were also associated with MACE. These results suggest that higher levels of neutrophil-enriched biomarkers may be predictive of MACE in patients with ACS, although higher-quality studies are needed to confirm these observations.
Topics: Humans; Acute Coronary Syndrome; Biomarkers; Neutrophils; Prognosis; Lipocalin-2; Peroxidase; Predictive Value of Tests; Time Factors; Risk Assessment; Male; Risk Factors; Female; Up-Regulation; Neutrophil Activation; Middle Aged; Aged
PubMed: 37594719
DOI: 10.1007/s12265-023-10425-2 -
Bone Apr 2024This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in... (Review)
Review
PURPOSE
This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in relation to fracture healing.
METHODS
A literature search was performed using the PubMed database. The quality of the articles was evaluated using critical appraisal checklists.
RESULTS
Thirty one studies were included in this review. These studies consistently support that neutrophils exert both beneficial and detrimental effects on bone regeneration, influenced by Tumor Necrosis Factor-α (TNF-α), Interleukin 8 (IL-8), mast cells, and macrophages. The N2 phenotype has recently emerged as one promoter of bone healing. The N1 phenotype has progressively been connected with inflammatory neutrophils during fracture healing.
CONCLUSIONS
This review has pinpointed various aspects and mechanisms of neutrophil influence on bone healing. The recognition of N1 and N2 neutrophil phenotypes potentially shed new light on the dynamic shifts taking place within the Fracture Hematoma (FH).
Topics: Humans; Neutrophils; Bone Regeneration; Fracture Healing; Fractures, Bone; Phenotype
PubMed: 38253189
DOI: 10.1016/j.bone.2024.117021 -
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