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Inflammation Research : Official... Mar 2024The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We investigated this issue by conducting a systematic review and meta-analysis of cell adhesion molecules in RA patients.
METHODS
We searched electronic databases from inception to 31 July 2023 for case-control studies assessing the circulating concentrations of immunoglobulin-like adhesion molecules (vascular cell, VCAM-1, intercellular, ICAM-1, and platelet endothelial cell, PECAM-1, adhesion molecule-1) and selectins (E, L, and P selectin) in RA patients and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively.
RESULTS
In 39 studies, compared to controls, RA patients had significantly higher concentrations of ICAM-1 (standard mean difference, SMD = 0.81, 95% CI 0.62-1.00, p < 0.001; I = 83.0%, p < 0.001), VCAM-1 (SMD = 1.17, 95% CI 0.73-1.61, p < 0.001; I = 95.8%, p < 0.001), PECAM-1 (SMD = 0.82, 95% CI 0.57-1.08, p < 0.001; I = 0.0%, p = 0.90), E-selectin (SMD = 0.64, 95% CI 0.42-0.86, p < 0.001; I = 75.0%, p < 0.001), and P-selectin (SMD = 1.06, 95% CI 0.50-1.60, p < 0.001; I = 84.8%, p < 0.001), but not L-selectin. In meta-regression and subgroup analysis, significant associations were observed between the effect size and use of glucocorticoids (ICAM-1), erythrocyte sedimentation rate (VCAM-1), study continent (VCAM-1, E-selectin, and P-selectin), and matrix assessed (P-selectin).
CONCLUSIONS
The results of our study support a significant role of cell adhesion molecules in mediating the interplay between RA and atherosclerosis. Further studies are warranted to determine whether the routine use of these biomarkers can facilitate the detection and management of early atherosclerosis in this patient group. PROSPERO Registration Number: CRD42023466662.
Topics: Humans; Intercellular Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1; Platelet Endothelial Cell Adhesion Molecule-1; E-Selectin; P-Selectin; Cell Adhesion Molecules; Arthritis, Rheumatoid; Biomarkers; Atherosclerosis
PubMed: 38240792
DOI: 10.1007/s00011-023-01837-6 -
Frontiers in Immunology 2023PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC.
AIM
To systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC.
METHODS
As of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4.
RESULTS
A total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I= 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P<0.05, I= 0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P<0.05, I= 18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P < 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P < 0.05).
CONCLUSION
ICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Triple Negative Breast Neoplasms; B7-H1 Antigen; Control Groups
PubMed: 37377959
DOI: 10.3389/fimmu.2023.1206689 -
International Journal of Molecular... Mar 2023This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular... (Meta-Analysis)
Meta-Analysis Review
Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment.
This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30-4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45-3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75-4.75; and DFS: HR 2.74; 95% CI, 2.09-3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1SOCS3 is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.
Topics: Humans; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Hepatocellular; Immunotherapy; Ligands; Liver Neoplasms; Tumor Microenvironment; Programmed Cell Death 1 Receptor
PubMed: 37047482
DOI: 10.3390/ijms24076495 -
Journal of Clinical Immunology Dec 2023Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have...
PURPOSE
Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have provided a detailed description of CD40L deficiency, reports of CD40 deficiency are scarce. Herein, we describe the characteristics of all reported patients with CD40 deficiency.
METHODS
The PubMed, Embase and Web of Science databases were searched for relevant literature published till 7th August 2023. Study deduplication and identification of relevant reports was performed using the online PICO Portal. The data were extracted using a pre-designed data extraction form and the SPSS software was used for analysis.
RESULTS
Systematic literature review revealed 40 unique patients with CD40 deficiency. Respiratory tract and gastrointestinal infections were the predominant clinical manifestations (observed in 93% and 57% patients, respectively). Sclerosing cholangitis has been reported in nearly one-third of patients. Cryptosporidium sp. (29%) and Pneumocystis jirovecii (21%) were the most common microbes identified. Very low to undetectable IgG levels and severely reduced/absent switch memory B cells were observed in all patients tested/reported. Elevated IgM levels were observed in 69% patients. Overall, splice-site and missense variants were the most common (36% and 32%, respectively) molecular defects identified. All patients were managed with immunoglobulin replacement therapy and antimicrobial prophylaxis was utilized in a subset. Hematopoietic stem cell transplantation (HSCT) has been performed in 45% patients (curative outcome observed in 73% of these patients). Overall, a fatal outcome was reported in 21% patients.
CONCLUSIONS
We provide a comprehensive description of all important aspects of CD40 deficiency. HSCT is a promising curative treatment option for CD40 deficiency.
Topics: Humans; CD40 Ligand; Cryptosporidiosis; Cryptosporidium; Hyper-IgM Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; CD40 Antigens; Immunoglobulin M; Lymphopenia
PubMed: 38129705
DOI: 10.1007/s10875-023-01633-1 -
Expert Review of Anti-infective Therapy Nov 2022Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma. Underlying and treatment-related variables may contribute to the development of infectious complications.
RESEARCH DESIGN AND METHODS
We conducted a systematic review and meta-analysis on the incidence of overall and severe (grade ≥3) infection in patients with hematological malignancies receiving CAR T-cells. Secondary outcomes included the specific rates of bacterial, viral and invasive fungal infection (IFI), and infection-related mortality. PubMed, Embase and Web of Science databases were searched from inception to 27 May 2022. Sensitivity analysis were performed according to the type of malignancy and study design (randomized clinical trials [RCTs] or observational studies).
RESULTS
Forty-five studies (34 RCTs) comprising 3,591 patients were included. The pooled incidence rates of overall and severe infection were 33.8% (I = 96.31%) and 16.2% (I = 74.41%). The respiratory tract was the most common site of infection. Most events were bacterial or viral, whereas the occurrence of IFI was rare. The pooled attributable mortality was 1.8% (I = 43.44%).
CONCLUSIONS
Infection is a frequent adverse event in patients receiving CAR T-cell therapy. Further research should address specific risk factors in this population.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Antigens, CD19; Hematologic Neoplasms; Neoplasms
PubMed: 36148506
DOI: 10.1080/14787210.2022.2128762 -
International Journal of Environmental... Apr 2023The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group... (Meta-Analysis)
Meta-Analysis Review
The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), = 0.65). Additionally, we found a significant increase in CD8CD38HLA-DR T-cells (SMD (1.10, 95% CI: (0.93, 1.28), < 0.00001) and CD4CD38HLA-DR T-cells (SMD (0.92, 95% CI: (0.32, 1.52), = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.
Topics: Humans; HIV Infections; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quality of Life; HIV-1; HLA-DR Antigens; CD4 Lymphocyte Count; Cardiovascular Diseases; Cholesterol; Viral Load
PubMed: 37174188
DOI: 10.3390/ijerph20095668 -
Alimentary Pharmacology & Therapeutics Aug 2015Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti-CTLA-4 agents, such as ipilimumab and... (Review)
Review
BACKGROUND
Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti-CTLA-4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune-related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common.
AIMS
To discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti-CTLA-4-associated colitis, and to present a management algorithm for it.
METHODS
We searched PubMed for studies published through October 2014 using the terms 'anti-CTLA,' 'ipilimumab,' 'tremelimumab,' 'colitis,' 'gastrointestinal,' 'immune-related adverse effect,' 'immunotherapy,' 'melanoma,' and 'diarrhoea.'
RESULTS
Watery diarrhoea is commonly associated with anti-CTLA-4 therapy (27-54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8-22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti-CTLA-4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid-resistant cases may respond to anti-tumour necrosis factor-alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy.
CONCLUSION
Given the increasing use of anti-CTLA-4 therapy, clinicians must be aware of related adverse events and their management.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; CTLA-4 Antigen; Colitis; Diarrhea; Humans; Immunotherapy; Infliximab; Ipilimumab; Melanoma; Skin Neoplasms; Tumor Necrosis Factor-alpha
PubMed: 26079306
DOI: 10.1111/apt.13281 -
Journal of Diabetes and Its... Apr 2022Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has... (Review)
Review
AIMS
Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has been observed in diabetes complications. This review aimed to systematically survey human studies published until 31st January 2022 for CD163 expression, in particular diabetes complications and additionally to investigate whether CD163 may be implicated as a biomarker of, and mediator in, the progression of diabetes complications.
METHODS
A systematic literature search undertaken in Scopus, Embase and Medline established 79 papers of relevance. Data extraction and assessment followed the PRISMA workflow.
RESULTS
Based on specific criteria, 11 studies totalling 821 participants were included in this review. CD163 was quantified in various forms including soluble, cell surface, and mRNA measures. This review found that soluble CD163 was upregulated in diabetes complications in various local body fluids and systemically in plasma or serum and therefore implicated in the progression of those complications. CD163+ cells and mRNA were variably expressed across diabetes complications.
CONCLUSIONS
CD163 was altered in series of diabetes complications and the circulating sCD163 has potential utility as an inflammation biomarker. The variable expression of CD163 on cell surfaces and its mRNA across different diabetes complications warrants further systematic investigation.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Diabetes Complications; Diabetes Mellitus; Humans; Inflammation; Monocytes; RNA, Messenger; Receptors, Cell Surface
PubMed: 35190247
DOI: 10.1016/j.jdiacomp.2022.108150 -
Oral Oncology Jun 2019Tumor associated macrophages (TAMs) are among the most abundant cells of the tumor microenvironment. Several studies have been performed to investigate whether TAM... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Tumor associated macrophages (TAMs) are among the most abundant cells of the tumor microenvironment. Several studies have been performed to investigate whether TAM markers, namely CD68 and CD163, could serve as prognostic factors in patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this systematic review and meta-analysis was to synthetize the available evidence of the literature about the role of CD68+ and CD163+ TAMs as prognostic factors in SCCHN.
MATERIALS AND METHODS
This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Meta-analysis of overall survival, disease-free survival and progression-free survival was performed using the inverse of variance test. A random- or a fixed- effect model was used on the basis of the presence of heterogeneity. Risk of bias assessment and subgroup analysis were also performed.
RESULTS
High stromal expression of CD163+ TAMs correlated with both poor overall survival (HR, 2.26; 95% CI: [1.47, 3.47]; P < 0.001) and progression-free survival (HR, 2.29; 95% CI: [1.11, 4.71]; P = 0.03). Conversely, abundance of CD68+ TAMs was not associated with overall survival (HR, 1.25; 95% CI: [0.86, 1.80]; P = 0.24) and disease-free survival (HR, 2.06; 95% CI: [0.84, 5.05]; P = 0.11).
CONCLUSIONS
Findings from this study revealed that whilst IHC analysis of the generic macrophage marker CD68+ has no prognostic utility in patients with SCCHN, the M2-like marker CD163+ predicts poor prognosis. Our data suggest that assessment of CD163+ TAMs in SCCHN has potential for future clinical use. Further well-standardized studies should be performed to confirm these results.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Cancer-Associated Fibroblasts; Disease Progression; Female; Head and Neck Neoplasms; Humans; Male; Prognosis; Receptors, Cell Surface; Squamous Cell Carcinoma of Head and Neck; Survival Analysis; Tumor Microenvironment
PubMed: 31109698
DOI: 10.1016/j.oraloncology.2019.04.019 -
International Journal of Molecular... Sep 2022Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid... (Review)
Review
Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.
Topics: Animals; Autoimmunity; CTLA-4 Antigen; Endometriosis; Female; Humans; Immune Checkpoint Proteins; Infertility; Prospective Studies
PubMed: 36142815
DOI: 10.3390/ijms231810902