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Frontiers in Immunology 2023Currently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Currently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand-1 (PD-L1) expression (≧50%). Pre-treatment or post-treatment serum soluble PD-L1 (sPD-L1) has been identified as a potential biomarker for assessing ICI efficacy through fixed-point observations. However, existing studies on sPD-L1 changes have produced inconsistent results or have had sample sizes too small to detect clinically meaningful effect sizes. To elucidate the role of sPD-L1, we conducted a collaborative individual patient data meta-analysis of PD-1 inhibitor treatments.
METHODS
We conducted a thorough search of articles in PubMed via Medline, Embase, Scopus, and Cochrane databases from inception to October 20, 2023. Trials were deemed eligible if they contained individual datasets for advanced NSCLC patients, including data on overall survival (OS)/progression-free survival (PFS), as well as pre- and post-treatment sPD-L1 levels after 3-4 cycles of PD-1 inhibitor treatments. Our analysis focused on patients who completed 3-4 cycles of PD-1 inhibitor treatments. The primary outcome measure was OS/PFS, and we assessed changes in sPD-L1 concentration pre- and post-treatment through ELISA analyses.
RESULTS
From our search, we identified a potential seven trials, encompassing 256 patients. Among these, two trials with 26 patients met the criteria for inclusion in our primary analyses. Over a median follow-up period of 10 months, pooled univariate analysis revealed that increases in sPD-L1 levels during PD-1 inhibitor treatment were not associated with OS (HR = 1.25; CI: 0.52-3.02)/PFS (HR = 1.42; CI: 0.61-3.30) when compared to cases with sPD-L1 decreases. Subgroup analyses indicated that the impact of sPD-L1 changes on overall mortality/progression-related mortality remained consistent regardless of gender, age, or the type of treatment (nivolumab or pembrolizumab).
CONCLUSION
Our findings suggest that changes in sPD-L1 levels during PD-1 inhibitor treatment do not significantly influence the prognosis of advanced NSCLC patients, regardless of gender, age, or treatment type. Continuous monitoring of sPD-L1 may not offer significant advantages compared to fixed-point observations.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; B7-H1 Antigen; Nivolumab
PubMed: 38115995
DOI: 10.3389/fimmu.2023.1308381 -
BMC Endocrine Disorders Dec 2023Several studies have highlighted the possible positive effects of soluble receptor for advanced glycation end products (sRAGE) against obesity. However, due to their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have highlighted the possible positive effects of soluble receptor for advanced glycation end products (sRAGE) against obesity. However, due to their inconsistent results, this systematic review and meta-analysis aimed to quantitatively evaluate and critically review the results of studies evaluating the relationship between sRAGE with obesity among adult population.
METHODS
In the systematic search, the eligibility criteria were as follows: studies conducted with a cross-sectional design, included apparently healthy adults, adults with obesity, or obesity-related disorders, aged over 18 years, and evaluated the association between general or central obesity indices with sRAGE.
RESULTS
Our systematic search in electronic databases, including PubMed, Scopus, and Embase up to 26 October, 2023 yielded a total of 21,612 articles. After removing duplicates, screening the titles and abstracts, and reading the full texts, 13 manuscripts were included in the final meta-analysis. According to our results, those at the highest category of circulating sRAGE concentration with median values of 934.92 pg/ml of sRAGE, had 1.9 kg/m lower body mass index (BMI) (WMD: -1.927; CI: -2.868, -0.986; P < 0.001) compared with those at the lowest category of sRAGE concentration with median values of 481.88 pg/ml. Also, being at the highest sRAGE category with the median values of 1302.3 pg/ml sRAGE, was accompanied with near 6 cm lower waist circumference (WC) (WMD: -5.602; CI: -8.820, -2.383; P < 0.001 with 86.4% heterogeneity of I) compared with those at the lowest category of sRAGE concentration with median values of 500.525 pg/ml. Individuals with obesity had significantly lower circulating sRAGE concentrations (WMD: -135.105; CI: -256.491, -13.72; P = 0.029; with 79.5% heterogeneity of I). According to the subgrouping and meta-regression results, country and baseline BMI were possible heterogeneity sources. According to Begg's and Egger's tests and funnel plots results, there was no publication bias.
CONCLUSION
According to our results, higher circulating sRAGE concentrations was associated with lower BMI and WC among apparently healthy adults. Further randomized clinical trials are warranted for possible identification of causal associations.
Topics: Adult; Humans; Middle Aged; Receptor for Advanced Glycation End Products; Cross-Sectional Studies; Obesity; Body Mass Index; Glycation End Products, Advanced; Weight Loss
PubMed: 38102636
DOI: 10.1186/s12902-023-01520-1 -
American Journal of Translational... 2023An evaluation of the inflammatory enzymatic interactions related to pulmonary function can help identify biomarkers for interventions or prophylactic measures to improve... (Review)
Review
Soluble epoxide hydrolase inhibitors for smoking-associated inflammatory lung diseases and chronic obstructive pulmonary disease: a meta-analytical systematic review of preclinical and clinical studies.
An evaluation of the inflammatory enzymatic interactions related to pulmonary function can help identify biomarkers for interventions or prophylactic measures to improve patient prognosis. This study aimed to determine the effect of epoxide hydrolase inhibition by GSK2256294 in different pulmonary inflammation models. A secondary search was performed using Medline/PubMed, Web of Science, SciELO, Cochrane Library, Embase, Academic Google, and gray literature by two independent reviewers, who analyzed the methodological quality and consistency of the data. Different variables were compared using a meta-analysis. A total of 86 studies were found, 4 of which were selected from the gray literature. Based on the eligibility criteria, two clinical and one preclinical studies were evaluated. GSK2256294 inhibited the soluble epoxide hydrolase enzyme in both clinical and preclinical models, exhibiting greater effectiveness in clinical studies and contributing to the anti-inflammatory activity mediated by the eicosatrienoic pathway by reducing the levels of dihydroxyeicosatrienoic acids and leukotoxin-diol. Overall, GSK2256294 was identified as a promising drug for controlling the deleterious manifestations of lung inflammation. Further clinical and preclinical studies are required to ensure consistency among the evidence and identify other biological activities mediated by GSK2256294.
PubMed: 38074809
DOI: No ID Found -
International Journal of Molecular... Nov 2023Brassinosteroids (BRs), the sixth major phytohormone, can regulate plant salt tolerance. Many studies have been conducted to investigate the effects of BRs on plant salt... (Meta-Analysis)
Meta-Analysis Review
Promotion of Ca Accumulation in Roots by Exogenous Brassinosteroids as a Key Mechanism for Their Enhancement of Plant Salt Tolerance: A Meta-Analysis and Systematic Review.
Brassinosteroids (BRs), the sixth major phytohormone, can regulate plant salt tolerance. Many studies have been conducted to investigate the effects of BRs on plant salt tolerance, generating a large amount of research data. However, a meta-analysis on regulating plant salt tolerance by BRs has not been reported. Therefore, this study conducted a meta-analysis of 132 studies to elucidate the most critical physiological mechanisms by which BRs regulate salt tolerance in plants from a higher dimension and analyze the best ways to apply BRs. The results showed that exogenous BRs significantly increased germination, plant height, root length, and biomass (total dry weight was the largest) of plants under salt stress. There was no significant difference between seed soaking and foliar spraying. However, the medium method (germination stage) and stem application (seedling stage) may be more effective in improving plant salt tolerance. BRs only inhibit germination in Solanaceae. BRs (2 μM), seed soaking for 12 h, and simultaneous treatment with salt stress had the highest germination rate. At the seedling stage, the activity of Brassinolide (CHO) was higher than that of Homobrassinolide (CHO), and post-treatment, BRs (0.02 μM) was the best solution. BRs are unsuitable for use in the germination stage when Sodium chloride is below 100 mM, and the effect is also weakest in the seedling stage. Exogenous BRs promoted photosynthesis, and antioxidant enzyme activity increased the accumulation of osmoregulatory and antioxidant substances and reduced the content of harmful substances and Na, thus reducing cell damage and improving plant salt tolerance. BRs induced the most soluble protein, chlorophyll a, stomatal conductance, net photosynthetic rate, Glutathione peroxidase, and root-Ca, with BRs causing Ca signals in roots probably constituting the most important reason for improving salt tolerance. BRs first promoted the accumulation of Ca in roots, which increased the content of the above vital substances and enzyme activities through the Ca signaling pathway, improving plant salt tolerance.
Topics: Brassinosteroids; Antioxidants; Salt Tolerance; Chlorophyll A; Seedlings; Plant Roots
PubMed: 38003311
DOI: 10.3390/ijms242216123 -
Clinical Nutrition Research Oct 2023Literature showed that soluble fiber has beneficial effects on cardiometabolic risk factors and leptin and adiponectin serum levels. Our aim in this meta-analysis was to...
Literature showed that soluble fiber has beneficial effects on cardiometabolic risk factors and leptin and adiponectin serum levels. Our aim in this meta-analysis was to determine the effect of soluble fiber supplementation on leptin and adiponectin serum levels. A systematic search was conducted using PubMed, Scopus, and ISI Web of Science for eligible trials up to December 2021. A random-effects model was used to pool calculated effect sizes. Our analysis showed that soluble fiber supplementation did not significantly affect adiponectin (standardized mean difference [SMD], -0.49 Hedges's, 95% confidence interval [CI], -1.20, 0.21, p value = 0.167; I = 95.4, p value < 0.001) and leptin (SMD, -0.8 Hedges's, 95% CI, -1.70, 0.08, p value = 0.076; I = 94.6, p value < 0.001) concentrations in comparison with placebo. However, in the subgroup, soluble fiber supplementation had a significant improvement in leptin concentration in overweight and obese patients (SMD, -0.22 Hedges's, 95% CI, -0.43, -0.01, p value = 0.048) and a non-significant beneficial effect in adiponectin level in female (SMD, 0.29 Hedges's, 95% CI, -0.13, 0.71, p value = 0.183) and diabetic patients (SMD, 0.32 Hedges's, 95% CI, -0.67, 1.32, p value = 0.526). A non-linear association between soluble fiber dosage and adiponectin (p < 0.001) was observed. Soluble fiber supplementation could not change the circulatory leptin and adiponectin levels. However, beneficial effects were seen in overweight and obese leptin, and increases in adiponectin may also be observed in female and diabetic patients. Further studies are needed to confirm this results.
PubMed: 37969941
DOI: 10.7762/cnr.2023.12.4.320 -
Medicine Nov 2023Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus,... (Meta-Analysis)
Meta-Analysis
Role of soluble urokinase type plasminogen activator receptor (suPAR) in predicting mortality, readmission, length of stay and discharge in emergency patients: A systematic review and meta analysis.
BACKGROUND
Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED.
METHODS
We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU.
RESULTS
A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82-22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35-9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16-1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40-0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84-4.56; I2 = 99%; P < .00001).
CONCLUSION
suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.
Topics: Humans; Female; Middle Aged; Male; Receptors, Urokinase Plasminogen Activator; Patient Discharge; Patient Readmission; Length of Stay; Biomarkers; Prognosis
PubMed: 37960735
DOI: 10.1097/MD.0000000000035718 -
Journal of Nephrology Mar 2024Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This... (Review)
Review
BACKGROUND
Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This systematic review evaluates the available literature regarding non-surgical interventions for cystinuria.
METHODS
Key electronic databases were searched for studies that described the clinical management of cystinuria with high diuresis, alkalinizing agents and thiol-based drugs that were published between 2000 and 2022. Observational studies were included if they contained clinical investigation with at least one previous or current episode of cystine stones, urine cystine levels > 250 mg/L and patients being managed with urinary dilution, alkalinizing agents or other pharmacological agents. All included studies were assessed for study design, patient characteristics and outcomes. A qualitative and critical analysis was performed whereby study quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Two authors performed the quality assessment and excluded the studies with a low MINORS score.
RESULTS
Fourteen studies met the review inclusion and quality criteria. Of the fourteen studies, two reported treatment using alkalinizing agents, six reported treatment using thiol-based drugs, and six reported combination treatment using alkalinizing agents and thiol-based drugs. These studies indicated that first-line therapies, including high fluid intake and urinary alkalinization, increased urine volume to > 3 L/day and urinary pH > 7.0, and were associated with reduced urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding thiol drugs, such as tiopronin and D-penicillamine, reduced urinary cystine levels, cystine crystal volume and increased cystine solubility, resulting in decreased cystine stone formation and stone recurrence rate. Further, combined intervention with alkalinizing agents and thiol-based drugs synergistically reduced stone recurrence.
CONCLUSION
Cystinuria treatment may require a combined approach of high diuresis, alkalinization and pharmacological interventions with regular monitoring of urinary pH, cystine levels, cystine crystal volume and solubility. However, poor adherence to treatment is relatively frequent, hence the pressing urgency for improved therapies and treatments.
Topics: Cystinuria; Humans; Cystine; Sulfhydryl Compounds; Treatment Outcome; Diuresis
PubMed: 37957454
DOI: 10.1007/s40620-023-01795-6 -
Cureus Sep 2023Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.
PubMed: 37905269
DOI: 10.7759/cureus.46185 -
Pharmacological Research Nov 2023Long-chain n-3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In... (Meta-Analysis)
Meta-Analysis
Long-chain n-3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: -1.26, 95% CI: -1.88 to -0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: -1.76, 95%CI: -3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: -0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: -2.67, 95%CI: -5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.
Topics: Humans; E-Selectin; P-Selectin; Randomized Controlled Trials as Topic; Cell Adhesion Molecules; Vascular Cell Adhesion Molecule-1; Fatty Acids; Fatty Acids, Omega-3; Dietary Supplements
PubMed: 37863453
DOI: 10.1016/j.phrs.2023.106963 -
Frontiers in Nutrition 2023To conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and...
Dietary intake of total vegetable, fruit, cereal, soluble and insoluble fiber and risk of all-cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies.
OBJECTIVES
To conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and insoluble fiber intake and risk of all causes, cardiovascular disease (CVD), and cancer mortality and quantitatively assess the dose-response relation.
METHODS
Eligible studies were identified by searching PubMed, Embase and Web of science before August 2023. Random effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CI) and restricted cubic splines to model the linear/non-linear association.
RESULTS
The summary RR for all-cause, CVD and cancer mortality of dietary fiber was 0.90 (95% CI: 0.86,0.93), 0.87 (0.84,0.91), 0.91 (0.88,0.93), respectively. Significant association was observed for all-cause and CVD mortality with fruit, vegetable cereal and soluble fiber intake and cancer mortality with cereal fiber intake. No significant association was found for insoluble fiber, vegetable or fruit fiber intake and cancer mortality. Dose-response analysis showed a significant non-linear relation of dietary fiber intake with all-cause mortality, and linear relation for others.
CONCLUSIONS
Higher dietary fiber including different type and food sources of fiber intake were associated with lower risk of mortality. Our findings provide more comprehensive evidence on dietary fiber intake with mortality.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier: CRD42022338837.
PubMed: 37854351
DOI: 10.3389/fnut.2023.1153165