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Medicine Nov 2023Duhuo-Jisheng decoction (DJD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of rheumatoid arthritis (RA)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Duhuo-Jisheng decoction (DJD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of rheumatoid arthritis (RA) patients could be improved by DJD. However, the existing evidence was not robust enough and controversial.
METHODS
Randomized controlled trials of DJD for RA were retrieved from Chinese and English databases from their inception to April 16, 2023. Meta-analysis was performed by Stata 17 software. We used subgroup analysis, meta-regression, and sensitivity analysis to identify potential sources of heterogeneity. The subgroup analysis and meta-regression were conducted from 6 aspects, including age, course of disease, course of treatment, interventions used in the experimental or control group, and random sequence generation. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger's test and funnel plots when the number of relevant studies was greater than or equal to 10.
RESULTS
Forty-two studies were included, involving 3635 patients and 19 outcome indicators. Meta-analysis showed that, compared with the routine disease-modifying antirheumatic drugs (rDMARDs), DJD could better improve the level of laboratory indicators, main symptoms and signs, and questionnaire scores of RA patients. The laboratory indicators included rheumatoid factor, T lymphocyte subpopulation (including CD4+, CD8+, and CD4+/CD8+), and inflammatory biomarkers (including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor-α, interleukin 6, interleukin 1β, and interleukin 1). The main symptoms and signs included the duration of morning stiffness, the number of joint tenderness, the number of swollen joints, and the grip strength of both hands. The questionnaire included visual analogue scale, health assessment questionnaire, and disease activity score in 28 joints. In addition, the adverse events of DJD treatment were significantly lower than those of rDMARDs. However, the results of a few subgroup analyses differed from the overall results. Furthermore, the publication bias assessment showed that, out of 11 evaluated results, 4 had publication bias.
CONCLUSION
DJD could be a satisfactory complementary and alternative therapy for RA. However, due to a small number of subgroup analysis results being different from the overall results, it should be verified by further studies.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hand Strength; Randomized Controlled Trials as Topic
PubMed: 37933004
DOI: 10.1097/MD.0000000000035513 -
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364 -
International Reviews of Immunology 2024Regulatory T cells (Tregs) play an important immunosuppressive role in inflammatory bowel disease (IBD). However, findings on the quantitative and functional changes of... (Meta-Analysis)
Meta-Analysis Review
Regulatory T cells (Tregs) play an important immunosuppressive role in inflammatory bowel disease (IBD). However, findings on the quantitative and functional changes of intestinal and circulating Tregs in patients with IBD are rather contradictory. We therefore conducted a meta-analysis on this issue. The pooled effect was assessed using the standardized mean difference (SMD) with a 95% confidence interval (CI), and subgroup analyses were performed to investigate heterogeneity. This analysis included 764 IBD (402 UC and 362 CD) patients and 341 healthy controls (HCs) pooled from 17 eligible studies. The percentage of circulating Tregs was significantly decreased in active IBD patients compared to HCs (SMD = -0.95, < 0.001) and inactive IBD patients (SMD = -0.80, < 0.001). There was no difference in the percentage of circulating Tregs between inactive IBD patients and HCs. The suppressive function of circulating Tregs was impaired in active IBD patients according to limited data (SMD = -0.75, = 0.02). Besides, the percentage of intestinal Tregs was significantly higher in inflamed regions than in non-inflamed regions (SMD = 0.85, < 0.001). Our study quantitatively summarized the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.
Topics: Humans; T-Lymphocytes, Regulatory; Intestinal Mucosa; Inflammatory Bowel Diseases; Intestines
PubMed: 37615427
DOI: 10.1080/08830185.2023.2249525 -
Molecular Psychiatry May 2024Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by...
Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by alterations in peripheral blood immune cell counts. However, it remains unclear whether these immunological changes are distinct in individuals experiencing suicidal ideation (SI) or suicidal behavior (SB), beyond the context of an MDE. This systematic review and meta-analysis aimed to examine peripheral immune cell profiles across samples with SI/SB and compare them to healthy controls or patients with MDE. A systematic literature search was conducted in MEDLINE, Embase, and PsycINFO for articles published from inception until June 12, 2023. Two independent reviewers screened the articles for inclusion, extracted data, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed using a random-effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for immune cell counts or ratios between groups with and without SI/SB. Heterogeneity across studies was assessed using the restricted maximum-likelihood estimator for tau statistic and I-statistic and tested by the Q test. Publication bias was evaluated using the Egger´s test and funnel plots. Meta-regression analyses were conducted to explore the potential moderating effects of age, gender, current or lifetime SI/SB, and the type of self-harming behavior (SI or SB). The study was registered with PROSPERO (CRD42023433089). The systematic review included 30 studies, with data from 19 studies included in the meta-analyses comprising 139 unique comparisons. Eleven different cell populations or ratios were included, comprising 1973 individuals with SI/SB and 5537 comparison subjects. White blood cell (WBC) and neutrophil counts were higher in individuals with SI/SB than in controls (WBC: SMD = 0.458; 95% CI = 0.367-0.548; p value ≤ 0.001; I = 0.002% and; Neutrophils: SMD = 0.581; 95% CI = 0.408-0.753; p < 0.001), indicating an inflammatory process. The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential marker, demonstrating a notable elevation in individuals with SI/SB (SMD = 0.695; 95% CI = 0.054-1.335; p value = 0.033; I = 94.281%; Q test p value ≤ 0.001). The elevated NLR appears to be primarily driven by the increase in neutrophil counts, as no significant differences were found in lymphocyte counts between groups. Comparisons among participants with and without SI/SB and depression revealed similar trends with increased NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) observed in depressed individuals with SI/SB compared to those without SI/SB. Broad alteration in the peripheral immune cell populations and their ratios were observed in individuals with SI/SB, indicating an immune activation or dysfunction. Notably, these immunological changes were also evident when comparing MDE individuals with and without SI/SB, suggesting that such immune dysfunction associated with suicidality cannot be solely attributed to or explained by depressive symptoms. The NLR, MLR, and PLR ratios, in combination with novel immune cellular and protein biomarkers, open new avenues in understanding the immunological underpinnings of SI/SB. These findings highlight the potential utility of immune markers as part of a multi-modal approach for risk stratification and therapeutic monitoring in SI/SB.
PubMed: 38802507
DOI: 10.1038/s41380-024-02587-5 -
Skin Health and Disease Dec 2023Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed... (Review)
Review
Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed death-1 (PD1) and anti-cytotoxic T-lymphocyte-associated protein (anti-CTLA4). However, a significant percentage of patients develop resistance to these immunotherapy drugs. Therefore, novel strategies were developed to target other aspects of the immune response. Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule found on natural killer cells and activated T-cells which negatively regulates T-cell proliferation and function. LAG-3 inhibitors interact with LAG-3 ligands on the surface of T-cells to block T-regulatory (Treg) cell activity, suppress cytokine secretion and restore dysfunctional effector T-cells which subsequently attack and destroy cancer cells. This review reports the dermatologic side effects associated with LAG-3 inhibitors used in the treatment of melanomas. Using PRISMA 2022 guidelines, a comprehensive literature review of PubMed, Google Scholar, Embase, Cochrane, and Web of Science databases was conducted. Three studies were identified that demonstrated that the use of LAG-3 inhibitors, whether as a single agent or in combination with other immune checkpoint inhibitors, resulted in stomatitis, pruritus, rash, dry skin, erythema, and vitiligo. Further research is warranted to assess the cutaneous adverse events observed with LAG-3 inhibitors in treating melanoma and to identify populations most vulnerable to such side effects.
PubMed: 38047262
DOI: 10.1002/ski2.296 -
International Immunopharmacology Sep 2023Many researches have reported the impairment of regulatory T cells (Tregs) in autoimmune hepatitis (AIH), whilst the change of Tregs in peripheral blood remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many researches have reported the impairment of regulatory T cells (Tregs) in autoimmune hepatitis (AIH), whilst the change of Tregs in peripheral blood remains controversial. We performed this systematic review and meta-analysis to clarify the numerical change of circulating Tregs in AIH patients compared with healthy individuals.
METHODS
Relevant studies were identified from Medline, PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and WanFang Data. Twenty-nine studies involving 968 AIH patients and 583 healthy controls were included. Subgroup analysis stratified by Treg definition or ethnicity was performed, and analysis of active-phase AIH was conducted.
RESULTS
The proportions of Tregs among CD4 T cells and PBMCs were generally decreased in AIH patients compared with healthy controls. Subgroup analysis showed that circulating Tregs identified by CD4CD25, CD4CD25Foxp3, CD4CD25CD127, and Tregs in Asian population were decreased among CD4 T cells in AIH patients. No significant change of CD4CD25Foxp3CD127 Tregs and Tregs in Caucasian population among CD4 T cells were found in AIH patients, whereas the number of studies was limited in these subgroups. Moreover, analysis of the active-phase AIH patients showed that Treg proportions were decreased generally, whereas no significant differences in Tregs/CD4 T cells were observed when markers CD4CD25Foxp3, CD4CD25Foxp3CD127 were used or in Caucasian population.
CONCLUSIONS
The proportions of Tregs among CD4 T cells and PBMCs were decreased in AIH patients compared with healthy controls generally, whereas Treg definition markers, ethnicity, and disease activity had influence on the results. Further large-scale and rigorous study is warranted.
Topics: Humans; T-Lymphocytes, Regulatory; Hepatitis, Autoimmune; CD4-Positive T-Lymphocytes; Interleukin-2 Receptor alpha Subunit; Ethnicity; Forkhead Transcription Factors
PubMed: 37390643
DOI: 10.1016/j.intimp.2023.110576 -
Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis.Biological Psychiatry Jan 2024A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and...
BACKGROUND
A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking.
METHODS
Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included.
RESULTS
A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, -0.04 to 0.32).
CONCLUSIONS
The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking.
PubMed: 38185237
DOI: 10.1016/j.biopsych.2023.11.029 -
Blood Advances Feb 2024Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing... (Meta-Analysis)
Meta-Analysis
Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing studies of ibrutinib, another small molecule inhibitor, suggested that these agents may predispose to opportunistic infections. We sought to systematically review the randomized controlled trial (RCT) evidence of venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia. We systematically reviewed RCTs comparing venetoclax therapy with active or placebo controls for patients with hematologic malignancies. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis, and we computed the probability of any increased risk (P[risk ratio (RR) > 1]) of IAEs or neutropenic complications. Seven RCTs were included, comprising 2067 patients. In CLL (n = 1032), there was a low probability of increased risk of high-grade (P[RR > 1] = 71.2%) and fatal IAEs (P[RR > 1] = 64.5%) and high-grade neutropenia (P[RR > 1] = 63.4%). There were insufficient data to perform a meta-analysis of IAEs in AML; however, 1 trial suggested an increased risk of IAEs with venetoclax. Furthermore, in AML (n = 642), venetoclax was associated with a high probability of increased risk of high-grade neutropenia (P[RR > 1] = 94.6%) and febrile neutropenia (P[RR > 1] = 90.6%). Our results suggest that venetoclax has a low probability of increased risk of IAEs or neutropenia in CLL. By contrast, there is likely increased risk of high-grade neutropenia and febrile neutropenia in AML. Importantly, our analyses did not identify any specific IAEs that would benefit from routine antimicrobial prophylaxis or pre-emptive testing.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Communicable Diseases; Febrile Neutropenia; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38154071
DOI: 10.1182/bloodadvances.2023011964 -
International Immunopharmacology Mar 2024Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain relief in cancer patients. This study aims to clarify the prognostic impact of opioid use in advanced NSCLC patients receiving ICI therapy.
METHODS
A systematic literature review was carried out using online databases before July 2023. The meta-analysis was used to clarify the correlation of opioid use with the overall survival (OS) or progression-free survival (PFS) of ICI-treated NSCLC patients, both of which were determined using hazard ratios (HRs) coupled with 95 % confidence intervals (CIs). Then, an independent cohort enrolling 181 NSCLC patients was utilized for validation. Finally, a comprehensive bioinformatics analysis based on TCGA cohort was performed to investigate the prognostic significance of opioid target genes (OTGs) and their correlation with immune infiltration in NSCLC patients.
RESULTS
A total of 8 studies enrolling 1174 patients were included in the meta-analysis. Opioid use was negatively associated with worse PFS (HR = 2.16, 95 %CI: 1.26-3.71) and OS (HR = 2.02, 95 %CI: 1.54-2.63) in ICI-treated NSCLC patients. The retrospective validation confirmed the above result and identified opioid use as an independent unfavorable predictor for PFS and OS in both the entire cohort and ICI subgroup. The bioinformatic analysis identified 14 prognostic OTGs (CYP17A1, PDYN, PYCARD, FGA, NTSR1, FABP1, HPCA, PENK, PDGFB, LIN7A, FKBP5, TYMS, CACNA1H and LDHA), most of which were correlated with immune infiltration in NSCLC. A risk model was constructed based on 14 OTGs and found to effectively stratify the clinical outcome in both the training and validation set, independent of age, gender and TNM staging system. The model was also significantly correlated with infiltration of activated dendritic cells, neutrophils and tumor infiltrating lymphocytes. Finally, a nomogram was constructed based on the model, age, gender and TNM stage, which could predict well the 1-, 3- and 5-year survival of NSCLC patients.
CONCLUSION
Opioid use is correlated with the poor clinical outcome in ICI-treated NSCLC patients. Precise pain management is highly advocated and opioids are recommended to be cautiously used in these patients. OTGs have the potential to be prognostic biomarkers for NSCLC patients and their role in tumor immunity needs to be further investigated.
Topics: Humans; Analgesics, Opioid; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Membrane Proteins; Opioid-Related Disorders; Retrospective Studies; Vesicular Transport Proteins
PubMed: 38325047
DOI: 10.1016/j.intimp.2024.111611 -
Cellular & Molecular Biology Letters Jan 2024Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine...
Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease's systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials.
Topics: Humans; Adenosine; Adenosine Deaminase; Arthritis, Rheumatoid; Inflammation; Quercetin; Adenosine Deaminase Inhibitors
PubMed: 38225555
DOI: 10.1186/s11658-024-00531-7