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Frontiers in Immunology 2019During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have...
During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
Topics: Animals; Antigens, CD20; B-Lymphocytes; Disease Progression; Humans; Immune System Diseases; Immunotherapy; Lymphocyte Depletion; Rituximab; Treatment Outcome
PubMed: 31555262
DOI: 10.3389/fimmu.2019.01990 -
Biochimica Et Biophysica Acta.... Jan 2023DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and... (Review)
Review
DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.
Topics: Humans; DNA Methylation; Leukocytes, Mononuclear; Biomarkers, Tumor; Circulating Tumor DNA; Neoplasms; Cell-Free Nucleic Acids
PubMed: 36270476
DOI: 10.1016/j.bbadis.2022.166583 -
International Journal of Molecular... Feb 2023Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC).... (Review)
Review
Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC). The identification of biomarkers predicting the response to NAC could be helpful for personalized treatment. This systematic review provides an overview of putative biomarkers at baseline that are predictive for a pCR following NAC. Embase, Medline and Web of Science were searched for articles published between January 2010 and August 2022. The articles had to meet the following criteria: patients with primary invasive TNBC without distant metastases and patients must have received NAC. In total, 2045 articles were screened by two reviewers resulting in the inclusion of 92 articles. Overall, the most frequently reported biomarkers associated with a pCR were a high expression of Ki-67, an expression of PD-L1 and the abundance of tumor-infiltrating lymphocytes, particularly CD8+ T cells, and corresponding immune gene signatures. In addition, our review reveals proteomic, genomic and transcriptomic markers that relate to cancer cells, the tumor microenvironment and the peripheral blood, which also affect chemo-sensitivity. We conclude that a prediction model based on a combination of tumor and immune markers is likely to better stratify TNBC patients with respect to NAC response.
Topics: Humans; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Proteomics; Lymphocytes, Tumor-Infiltrating; Biomarkers; Tumor Microenvironment
PubMed: 36769287
DOI: 10.3390/ijms24032969 -
The Journal of Allergy and Clinical... Feb 2018The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the...
The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the broad field of allergy and immunology. This particular assignment was to cover the topic of eosinophils. In an attempt to highlight major ideas, themes, trends, and advances relevant to basic and clinical aspects of eosinophil biology, a search of articles published since 2015 in the Journal of Allergy and Clinical Immunology and other high-impact journals was performed. Articles were then reviewed and organized, and then key findings were summarized. Given space limitations, many outstanding articles could not be included, but the hope is that what follows provides a succinct overview of recently published work that has significantly added to our knowledge of eosinophils and eosinophil-associated diseases.
Topics: Eosinophils; Humans; Immune System Diseases
PubMed: 29045815
DOI: 10.1016/j.jaci.2017.09.022 -
BMC Medicine Nov 2020Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis.
METHODS
We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria.
RESULTS
A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence.
CONCLUSION
In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility.
TRIAL REGISTRATION
PROSPERO CRD42017069131 .
Topics: Female; Humans; Lymphocytes; Male; Neoplasms; Neutrophils; Prognosis; Survival Analysis
PubMed: 33213430
DOI: 10.1186/s12916-020-01817-1 -
Annals of Internal Medicine Jul 2012Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American... (Review)
Review
DESCRIPTION
Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
METHODS
These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).
Topics: Acute Coronary Syndrome; Adult; Blood Banks; Child; Decision Support Techniques; Erythrocyte Transfusion; Guideline Adherence; Hemoglobin A; Hospitalization; Humans; Randomized Controlled Trials as Topic; United States
PubMed: 22751760
DOI: 10.7326/0003-4819-157-1-201206190-00429 -
PloS One 2016Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment... (Review)
Review
BACKGROUND AND OBJECTIVE
Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to evaluate the presence of biomarkers in pulpitis.
METHODS
The electronic databases of MEDLINE, EMBASE, Scopus and other sources were searched for English and non-English articles published through February 2015. Two independent reviewers extracted information regarding study design, tissue or analyte used, outcome measures, results and conclusions for each article. The quality of the included studies was assessed using a modification of the Newcastle-Ottawa-Scale.
RESULTS AND CONCLUSIONS
From the initial 847 publications evaluated, a total of 57 articles were included in this review. In general, irreversible pulpitis was associated with different expression of various biomarkers compared to normal controls. These biomarkers were significantly expressed not only in pulp tissue, but also in gingival crevicular fluid that can be collected non-invasively, and in dentin fluid that can be analyzed without extirpating the entire pulpal tissue. Such data may then be used to accurately differentiate diseased from healthy pulp tissue. The interplay of pulpal biomarkers and their potential use for a more accurate and biologically based diagnostic tool in endodontics is envisaged.
Topics: Antimicrobial Cationic Peptides; Biomarkers; Cytokines; Databases, Factual; Dental Pulp; Enzymes; Humans; Inflammation; Leukocytes; Peptide Hydrolases
PubMed: 27898727
DOI: 10.1371/journal.pone.0167289 -
Pharmacological Research Apr 2023Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell... (Meta-Analysis)
Meta-Analysis Review
Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.
Topics: Humans; Adult; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Chronic Disease; Multiple Myeloma; Recurrence; Cell- and Tissue-Based Therapy
PubMed: 36963592
DOI: 10.1016/j.phrs.2023.106742 -
Experimental Hematology Jan 2021Periodontitis is a chronic inflammatory disease with local and systemic implications. Evidence suggests consistent hematologic changes associated with periodontitis. Our... (Meta-Analysis)
Meta-Analysis
Periodontitis is a chronic inflammatory disease with local and systemic implications. Evidence suggests consistent hematologic changes associated with periodontitis. Our aim was to critically appraise the available evidence on hemogram, leukogram, and thrombogram alterations in otherwise healthy patients suffering from periodontitis when compared with controls. For this systematic review (SR), we searched MEDLINE, Web of Science, EMBASE, and the Cochrane Library (CENTRAL) for studies published up to June 2020. Both observational and interventional studies with baseline standard hematologic levels were included. Outcomes of interest were baseline hemogram, leukogram, and thrombogram values and the impact of periodontitis treatment on these outcomes. Upon risk of bias assessment, data extraction and both qualitative and quantitative (standardized mean differences) analyses were performed. Random-effects meta-analyses were performed to provide pooled estimates. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed (PROSPERO Reg. No. CRD42020164531). A total of 45 studies, eight intervention and 37 case-control studies, were identified after the final search of 3,012 titles. Following quality assessment, 43 articles were deemed to have low risk of bias, and two articles moderate risk. Meta-analyses confirmed that periodontitis was associated with both white and red cell lineages. Severe chronic periodontitis was associated with greater white blood cell counts (mean difference [MD] = 0.53, 95% confidence interval [CI]: 0.26-0.79) when compared with controls. Periodontitis was associated with a larger number of neutrophils (MD = 7.16%, 95% CI: 5.96-8.37) and lower mean platelet volume (MD = 0.30 fL, 95% CI: 0.49 to -0.10) compared with healthy participants. Nonsurgical periodontal treatment was associated with a decrease in white blood cell (WBC) levels (MD = 0.28 10/L, 95% CI: -0.47 to -0.08) in patients with chronic periodontitis. Periodontitis is associated with hematologic changes (Strength of Recommendation Taxonomy [SORT] A recommendation). Higher WBC levels, higher neutrophil levels, higher erythrocyte sedimentation rate, and lower mean platelet volumes are the most common blood count findings. The association between periodontitis and WBC could be causal in nature. Further assessment to determine whether periodontitis causes changes in circulating blood cells and to identify the molecular mechanisms underlying these associations is warranted.
Topics: Blood Cell Count; Blood Cells; Blood Sedimentation; Humans; Mean Platelet Volume; Periodontitis
PubMed: 33068648
DOI: 10.1016/j.exphem.2020.10.001 -
Neonatology 2021The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related...
BACKGROUND
The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded.
METHODS
A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded.
RESULTS
We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively.
CONCLUSION
The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.
Topics: Aged; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Reference Values; Retrospective Studies; Spinal Puncture
PubMed: 34818234
DOI: 10.1159/000517630