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Therapeutic Advances in Gastroenterology 2023Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need.... (Review)
Review
BACKGROUND
Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages.
OBJECTIVE
To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD.
DESIGN
Systematic scoping review.
DATA SOURCES AND METHODS
We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included.
RESULTS
From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn's disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase-associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior.
CONCLUSION
Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker.
REGISTRATION
https://osf.io/kes9a.
PubMed: 36923488
DOI: 10.1177/17562848231155987 -
Canadian Journal of Gastroenterology &... 2022Nonalcoholic steatohepatitis (NASH) and liver fibrosis are the most common complications of nonalcoholic fatty liver disease (NAFLD). In this systematic review and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Nonalcoholic steatohepatitis (NASH) and liver fibrosis are the most common complications of nonalcoholic fatty liver disease (NAFLD). In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the association of neutrophil to lymphocyte ratio (NLR) with NASH and fibrosis in patients with NAFLD.
METHODS
PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment.
RESULTS
Thirteen studies were included in our study. The pooled results showed that NAFLD patients with significant NASH had elevated levels of NLR compared to those with nonsignificant or without NASH (SMD = 0.97, 95% CI = 0.59-1.39, < 0.001). The pooled sensitivity and specificity of NLR were 78.16% (95% CI = 73.70%-82.04%), and 76.93% (95% CI = 70.22%-82.50%), respectively. In addition, NAFLD patients with significant liver fibrosis had elevated levels of NLR compared to those with nonsignificant or without fibrosis (SMD = 1.59, 95% CI = 0.76-2.43, < 0.001). The pooled sensitivity and specificity of NLR were 82.62% (95% CI = 70.235%-90.55%) and 81.22% (95% CI = 75.62%-85.78%), respectively.
CONCLUSION
Our findings support NLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of NASH and fibrosis among patients with NAFLD.
Topics: Humans; Prognosis; Non-alcoholic Fatty Liver Disease; Neutrophils; Liver Cirrhosis; Lymphocytes
PubMed: 37601979
DOI: 10.1155/2022/1554079 -
Clinical Orthopaedics and Related... May 2017In the assessment of possible periprosthetic knee infection, various imaging modalities are used without consensus regarding the most accurate technique. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the assessment of possible periprosthetic knee infection, various imaging modalities are used without consensus regarding the most accurate technique.
QUESTIONS/PURPOSES
To perform a meta-analysis to compare the accuracy of various applied imaging modalities in the assessment of periprosthetic knee infection.
METHODS
A systematic review and meta-analysis was conducted with a comprehensive search of MEDLINE and Embase in accordance with the PRISMA and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) recommendations to identify clinical studies in which periprosthetic knee infection was investigated with different imaging modalities. The sensitivity and specificity of each imaging technique were determined and compared with the results of microbiologic and histologic analyses, intraoperative findings, and clinical followup of more than 6 months. A total of 23 studies, published between 1990 and 2015, were included for meta-analysis, representing 1027 diagnostic images of symptomatic knee prostheses. Quality of the included studies showed low concerns regarding external validity, whereas internal validity indicated more concerns regarding the risk of bias. The most important concerns were found in the lack of uniform criteria for the diagnosis of a periprosthetic infection and the flow and timing of the included studies. Differences among techniques were tested at a probability less than 0.05 level. Where there was slight overlap of confidence intervals for two means, it is possible for the point estimates to be statistically different from one another at a probability less than 0.05. The z-test was used to statistically analyze differences in these situations.
RESULTS
Bone scintigraphy was less specific than all other modalities tested (56%; 95% CI, 0.47-0.64; p < 0.001), and leukocyte scintigraphy (77%; 95% CI, 0.69-0.85) was less specific than antigranulocyte scintigraphy (95%; 95% CI, 0.88-0.98; p < 0.001) or combined leukocyte and bone marrow scintigraphy (93%; 95% CI, 0.86-0.97; p < 0.001). Fluorodeoxyglucose positron emission tomography (FDG-PET) (84%; 95% CI, 0.76-0.90) was more specific than bone scintigraphy (56%; 95% CI, 0.47-0.64; p < 0.001), and less specific than antigranulocyte scintigraphy (95%; 95% CI, 0.88-0.98; p = 0.02) and combined leukocyte and bone marrow scintigraphy (93%; 95% CI, 0.86-0.97; p < 0.001). Leukocyte scintigraphy (88%; 95% CI, 0.81-0.93; p = 0.01) and antigranulocyte scintigraphy (90%; 95% CI, 0.78-0.96; p = 0.02) were more sensitive than FGD-PET (70%; 95% CI, 0.56-0.81). However, because of broad overlapping of confidence intervals, no differences in sensitivity were observed among the other modalities, including combined bone scintigraphy (93%; 95% CI, 0.85-0.98) or combined leukocyte and bone marrow scintigraphy (80%; 95% CI, 0.66-0.91; p > 0.05 for all paired comparisons).
CONCLUSIONS
Based on current evidence, antigranulocyte scintigraphy and combined leukocyte and bone marrow scintigraphy appear to be highly specific imaging modalities in confirming periprosthetic knee infection. Bone scintigraphy was a highly sensitive imaging technique but lacks the specificity needed to differentiate among various conditions that cause painful knee prostheses. FDG-PET may not be the preferred imaging modality because it is more expensive and not more effective in confirming periprosthetic knee infection.
LEVEL OF EVIDENCE
Level III, diagnostic study.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Bone Marrow; Child; Child, Preschool; Female; Fluorodeoxyglucose F18; Granulocytes; Humans; Knee Joint; Knee Prosthesis; Leukocytes; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prosthesis-Related Infections; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Treatment Outcome; Young Adult
PubMed: 28050818
DOI: 10.1007/s11999-016-5218-0 -
Frontiers in Immunology 2021The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may...
The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may be associated with these antibodies. In this review we analyze clinicopathological, immunologic and outcome features of anti-Dsc autoimmune blistering diseases patients, to improve their diagnosis and management. We conducted a systematic search of PubMed and Embase (1990-present) for studies reporting cases of autoimmune blistering diseases with anti-Dsc antibodies. We classified the selected patients as patients with exclusively anti-Dsc autoantibodies, and patients with anti-Dsc and other autoantibodies. Of 93 cases with anti-Dsc autoantibodies included, 38 (41%) had exclusively these antibodies. Only 18% of patients presented with the typical clinicopathological phenotype of pemphigus vulgaris or pemphigus foliaceous. Mucosal involvement was seen in approximately half of the patients. Up to 18% of cases were associated with neoplasms. Acantholysis was described in 54% of cases with histopathological information. Treatments and outcomes vary in the different clinical phenotypes. The presence of anti-Dsc antibodies must be suspected mainly in those patients with either atypical pemphigus, in special with clinical pustules, or in cases showing intraepithelial or dermal neutrophilic/eosinophilic infiltrate on histological examination and dual pattern by direct immunofluorescence examination.
Topics: Acantholysis; Animals; Autoantibodies; Autoimmunity; Desmocollins; Desmogleins; Eosinophils; Humans; Neutrophils; Pemphigus; Phenotype; Skin
PubMed: 34567003
DOI: 10.3389/fimmu.2021.740820 -
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 -
Journal of Alzheimer's Disease : JAD 2019TREM2 (triggering receptor expressed on myeloid cells 2) gene variants were reported to increase the risk of Alzheimer's disease (AD) and even other neurodegenerative... (Meta-Analysis)
Meta-Analysis
TREM2 (triggering receptor expressed on myeloid cells 2) gene variants were reported to increase the risk of Alzheimer's disease (AD) and even other neurodegenerative diseases (frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS)), but so far, no definite conclusion has been drawn. The aim of our systematic review and meta-analysis was to investigate the role of TREM2 variants in neurodegenerative diseases. A total of 39 papers (including 26 case-control studies and 13 case reports) were retrieved from PubMed, MEDLINE, EMBASE, and the Cochrane library in this study. A fixed effect model was used to pool results in the analysis. Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven. Rs75932628 also increased risk of PD in North Americans and FTD, but not PD in Europeans or ALS. In the systematic review, 12 biallelic TREM2 mutations (e.g., rs104894002, rs201258663 (T66M), and rs386834144, etc.) have been described to cause Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) in 14 families. And homozygous mutations also have been reported to cause FTD without typical bone phenotypes in 7 families. This study demonstrates that multiple variants in TREM2 have association with the onset of AD, FTD, and PD in North Americans and also play a key role in the phenotypes of the rare familial genetic disorder.
Topics: Alzheimer Disease; Frontotemporal Dementia; Genetic Predisposition to Disease; Genetic Variation; Humans; Lipodystrophy; Membrane Glycoproteins; Neurodegenerative Diseases; Osteochondrodysplasias; Parkinson Disease; Polymorphism, Single Nucleotide; Receptors, Immunologic; Subacute Sclerosing Panencephalitis
PubMed: 30883352
DOI: 10.3233/JAD-181038 -
Allergy Mar 2016Chronic spontaneous urticaria (CSU) is defined as persistent wheals, angioedema, or both lasting for >6 weeks due to known or unknown causes. Some epidemiological... (Meta-Analysis)
Meta-Analysis Review
Chronic spontaneous urticaria (CSU) is defined as persistent wheals, angioedema, or both lasting for >6 weeks due to known or unknown causes. Some epidemiological studies and case reports suggest that internal parasite infections (PI) can cause CSU. Here, we provide a systematic overview of published findings on the prevalence and relevance of PI in CSU and we discuss possible pathomechanisms. The prevalence of PI in CSU was investigated by 39 independent studies and comorbidity reportedly ranged from 0 to 75.4% (two-thirds of these studies reported infection rates of 10% or less). The prevalence of PI in adult and pediatric CSU patients ranged from 0% to 75.4% and from 0% to 37.8%, respectively. CSU patients were more often diagnosed with protozoa and had a significantly higher risk of toxocariasis seropositivity and Anisakis simplex sensitization when compared to healthy controls. Patients with chronic urticaria more frequently had seropositivity of fasciolosis, Anisakis simplex sensitization, and the presence of Blastocystis hominis allele 34 (ST3) as compared with control subjects. In 21 studies, efficacy of treatment with antiparasitic drugs ranged from 0 to 100% (35.7% of 269 CSU patients benefitted). In 9 (42.8%) of 21 studies, more than 50% of efficacy was observed. The reported rate of urticaria comorbidity in PI patients in 18 independent studies is 1-66.7%. Urticaria including CSU might be a quite common symptom of strongyloidiasis and blastocystosis. Pathogenic mechanisms in CSU due to PI may include specific IgE, Th2 cytokine skewing, eosinophils, activation of the complement, and the coagulation systems.
Topics: Adult; Age Factors; Animals; Antigen-Antibody Complex; Case-Control Studies; Child; Child, Preschool; Chronic Disease; Complement System Proteins; Cytokines; Eosinophils; Host-Pathogen Interactions; Humans; Immunoglobulin E; Parasitic Diseases; Prevalence; Risk Factors; Th2 Cells; Urticaria
PubMed: 26648083
DOI: 10.1111/all.12818 -
Oral Oncology Dec 2022Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment... (Meta-Analysis)
Meta-Analysis Review
Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment (TME). In this systematic review and meta-analysis, studies assessing tumor infiltration with CD68+, iNOS+, HLA-DR+, CD11b+, CD163+, CD206+, and CD204+TAMs were included, and correlation to survival hazard was studied. A low number of CD68+TAMs correlated to better overall survival (OS) in multivariate analysis (HR 1.36 95 %CI (1.07-1.72) P = .01). CD68+TAMs did not correlate to disease free survival (DFS), disease specific survival (DSS), progression free survival (PFS), or recurrence free survival (RFS). A low number of CD163+TAMs correlated to better OS in uni- and multivariate analysis (resp. HR 2.65 95 %CI (1.57-4.46) P = .01 and HR 2.42 95 %CI (1.72-3.41) P < .001). A low number of CD163+TAMs also correlated to better DFS and PFS, whereas a low number of CD204+TAMs only correlated to PFS. While IHC analysis of pan macrophage marker CD68 and M2-like marker CD163 both show prognostic utility in OS, CD163 is a stronger prognosticator, as indicated by multivariate meta-analysis. CD163+TAMs also correlate to DFS and PFS; outcomes that are more relevant to patients, thus showing promising results for future clinical implementation.
Topics: Humans; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tumor-Associated Macrophages; Antigens, Differentiation, Myelomonocytic; Tumor Microenvironment; Head and Neck Neoplasms
PubMed: 36335818
DOI: 10.1016/j.oraloncology.2022.106227 -
Transfusion Sep 2015Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound... (Review)
Review
BACKGROUND
Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia.
STUDY DESIGN AND METHODS
We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated donors.
RESULTS
Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean "same-day" neutrophil increments of 3.35 × 10(9) ± 1.24 × 10(9) /L and mean overall posttransfusion neutrophil increments of 2.46 × 10(9) ± 0.85 × 10(9) /L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT-related HLA alloimmunization.
CONCLUSION
In patients with IF, donor-stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable.
Topics: Female; Fusariosis; Granulocytes; Humans; Leukocyte Transfusion; Male
PubMed: 25857209
DOI: 10.1111/trf.13099 -
Head & Neck Feb 2023Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also... (Meta-Analysis)
Meta-Analysis Review
Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14-2.82; PFS, HR = 1.88, 95CI%, 1.26-2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer.
Topics: Humans; Hypopharyngeal Neoplasms; Lymphocyte Count; Lymphocytes; Neutrophils; Prognosis
PubMed: 36367335
DOI: 10.1002/hed.27246