-
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1... (Meta-Analysis)
Meta-Analysis
Prognostic significance of programmed cell death ligand 1 blood markers in non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1 (PD-L1) in peripheral blood, including soluble form (sPD-L1), expression on circulating tumor cells (CTCs PD-L1) and exosomes (exoPD-L1), are minimally invasive and promising markers for patient selection and management, but their prognostic significance remains inconclusive. Here, we performed a meta-analysis for the prognostic value of PD-L1 blood markers in NSCLC patients treated with ICIs.
METHODS
Eligible studies were obtained by searching PubMed, EMBAS, Web of Science, and Cochrane Library prior to November 30, 2023. The associations between pre-treatment, post-treatment and dynamic changes of blood PD-L1 levels and progression-free survival (PFS)/over survival (OS) were analyzed by estimating hazard ratio (HR) and 95% confidence interval (CI).
RESULTS
A total of 26 studies comprising 1606 patients were included. High pre- or post-treatment sPD-L1 levels were significantly associated with worse PFS (pre-treatment: HR=1.49, 95%CI 1.13-1.95; post-treatment: HR=2.09, 95%CI 1.40-3.12) and OS (pre-treatment: HR=1.83, 95%CI 1.25-2.67; post-treatment: HR=2.60, 95%CI 1.09-6.20, P=0.032). High pre-treatment exoPD-L1 levels predicted a worse PFS (HR=4.24, 95%CI 2.82-6.38, P<0.001). Pre-treatment PD-L1 CTCs tended to be correlated with prolonged PFS (HR=0.63, 95%CI 0.39-1.02) and OS (HR=0.58, 95%CI 0.36-0.93). Patients with up-regulated exoPD-L1 levels, but not sPD-L1, after ICIs treatment had significantly favorable PFS (HR=0.36, 95%CI 0.23-0.55) and OS (HR=0.24, 95%CI 0.08-0.68).
CONCLUSION
PD-L1 blood markers, including sPD-L1, CTCs PD-L1 and exoPD-L1, can effectively predict prognosis, and may be potentially utilized for patient selection and treatment management for NSCLC patients receiving ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; B7-H1 Antigen; Biomarkers, Tumor; Prognosis
PubMed: 38915398
DOI: 10.3389/fimmu.2024.1400262 -
Nutrition & Metabolism Jun 2024There are contradictory effects regarding the effect of NAD + precursor on glucose metabolism and liver enzymes. In order to obtain a better viewpoint from them,...
Changes in glucose metabolism, C-reactive protein, and liver enzymes following intake of NAD + precursor supplementation: a systematic review and meta-regression analysis.
BACKGROUND
There are contradictory effects regarding the effect of NAD + precursor on glucose metabolism and liver enzymes. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD + precursor supplementation on glucose metabolism, C-reactive protein (CRP), and liver enzymes.
METHODS
PubMed/MEDLINE, Web of Science, SCOPUS, and Embase databases were searched using standard keywords to identify all controlled trials investigating the glucose metabolism, CRP, and liver enzymes effects of NAD + precursor. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes.
RESULTS
Forty-five articles with 9256 participants' were included in this article. The pooled findings showed that NAD + precursor supplementation had a significant increase in glucose (WMD: 2.17 mg/dL, 95% CI: 0.68, 3.66, P = 0.004) and HbA1c (WMD: 0.11, 95% CI: 0.06, 0.16, P < 0.001) as well as a significant decrease in CRP (WMD: -0.93 mg/l, 95% CI -1.47 to -0.40, P < 0.001) compared with control group, and was not statistically significant with respect to insulin and homeostasis model assessment of insulin resistance (HOMA-IR). However, we found no systemic changes in aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase (ALP) levels after NAD + precursor supplementation. The results of the subgroup analysis showed that the intake of NAD + precursor during the intervention of more than 12 weeks caused a greater increase in the glucose level. Furthermore, Nicotinic acid supplementation (NA) causes a greater increase in glucose and HbA1c levels than nicotinamide (NE) supplementation.
CONCLUSIONS
Overall, these findings suggest that NAD + precursor supplementation might have an increase effect on glucose metabolism as well as a decrease in CRP.
PubMed: 38915015
DOI: 10.1186/s12986-024-00812-0 -
PloS One 2024Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and disability within this patient demographic. Presently, numerous studies have been conducted to investigate the underlying causes of stroke in individuals with T2DM, yet the findings exhibit inconsistencies.
OBJECTIVE
This paper aims to consolidate and summarize the available evidence concerning the influential factors contributing to stroke among patients diagnosed with T2DM.
METHODS
We conducted a comprehensive search across multiple databases, including Cochrane Library, PubMed, Web Of Science, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Weipu up to August 2023. Google Scholar was also searched to retrieve gray literature. We calculated odds ratios (OR) and 95% confidence intervals (CI) using Stata software.
RESULTS
Our analysis encompassed 43 observational studies, exploring factors across sociodemographic, biochemical, complications, and hypoglycemic agent categories. The findings identified several risk factors for stroke in patients with T2DM: age, gender, T2DM duration, hypertension, body-mass index (BMI), smoking, Glycated hemoglobin (HbA1c), estimated Glomerular Filtration Rate (eGFR), albuminuria, Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), Coronary heart disease (CHD), Atrial fibrillation (AF), diabetic retinopathy (DR), Peripheral vascular disease (PVD), and carotid plaque. Conversely, exercise, High density lipoprotein cholesterol (HDL-C), metformin (MET), pioglitazone, and metformin combination therapy emerged as protective factors.
CONCLUSION
This study underscores the multitude of influencing factors contributing to stroke in people with T2DM patients, among which the microvascular complications of T2DM play an most important role. Therefore, we emphasize the importance of screening for microvascular complications in patients with T2DM. However, due to limitations arising from the number of articles reviewed, there remain areas where clarity is lacking. Further research efforts are warranted to expand upon and reinforce our current findings.
Topics: Diabetes Mellitus, Type 2; Humans; Stroke; Risk Factors; Hypoglycemic Agents; Glycated Hemoglobin
PubMed: 38913694
DOI: 10.1371/journal.pone.0305954 -
Medicine Jun 2024Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients.
METHODS
We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value.
RESULTS
In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%.
CONCLUSION
Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.
Topics: Humans; Sepsis; Prognosis; Biomarkers; Blood Proteins; Antimicrobial Cationic Peptides; Sensitivity and Specificity; Critical Illness; Pore Forming Cytotoxic Proteins
PubMed: 38905400
DOI: 10.1097/MD.0000000000038525 -
PloS One 2024To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome (AAS) in patients presenting with symptoms suggestive of AAS.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2024. Additionally, the reference lists of included studies and other systematic reviews were thoroughly searched. All diagnostic accuracy studies that assessed the use of ADD-RS alone or with D-Dimer for diagnosing AAS compared with a reference standard test (e.g. computer tomographic angiography (CTA), ECG-gated CTA, echocardiography, magnetic resonance angiography, operation, or autopsy) were included. Two reviewers independently selected and extracted data. Risk of bias was appraised using QUADAS-2 tool. Data were synthesised using hierarchical meta-analysis models.
RESULTS
We selected 13 studies from the 2017 citations identified, including six studies evaluating combinations of ADD-RS alongside D-dimer>500ng/L. Summary sensitivities and specificities (95% credible interval) were: ADD-RS>0 94.6% (90%, 97.5%) and 34.7% (20.7%, 51.2%), ADD-RS>1 43.4% (31.2%, 57.1%) and 89.3% (80.4%, 94.8%); ADD RS>0 or D-Dimer>500ng/L 99.8% (98.7%, 100%) and 21.8% (12.1%, 32.6%); ADD RS>1 or D-Dimer>500ng/L 98.3% (94.9%, 99.5%) and 51.4% (38.7%, 64.1%); ADD RS>1 or ADD RS = 1 with D-dimer>500ng/L 93.1% (87.1%, 96.3%) and 67.1% (54.4%, 77.7%).
CONCLUSIONS
Combinations of ADD-RS and D-dimer can be used to select patients with suspected AAS for imaging with a range of trade-offs between sensitivity (93.1% to 99.8%) and specificity (21.8% to 67.1%).
Topics: Humans; Fibrin Fibrinogen Degradation Products; Aortic Dissection; Syndrome; Sensitivity and Specificity; Acute Disease; Computed Tomography Angiography; Acute Aortic Syndrome
PubMed: 38905181
DOI: 10.1371/journal.pone.0304401 -
Nutrients May 2024(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on... (Meta-Analysis)
Meta-Analysis Review
(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on blood lipid levels and glucose levels in humans through a systematic review and meta-analysis. (2) Methods: We extensively searched four databases, including PubMed, Web of Science, Embase, and the Cochrane Library, up to February 2024. To assess the collective impact of garlic and its supplements on fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), an analysis was conducted using a random effects model. Subgroup analyses were performed when < 50%. (3) Result: We found that the garlic intervention was effective in controlling FBG (mean difference = -7.01; 95% CI: -8.53, -5.49, < 0.001), HbA1c (mean deviation = -0.66; 95% CI: -0.76, -0.55, < 0.001, = 62.9%), TC (mean difference = -14.17; 95% CI: -19.31, -9.03, < 0.001), and LDL-C (mean difference = -8.20; 95% CI: -15.58, -0.81, = 0.03); moreover, it also increased the level of HDL-C in humans (mean difference = 2.06; 95% CI: 1.54, 2.59; < 0.001). Nonetheless, the intervention involving garlic did not yield a substantial impact on triglyceride (TG) levels. (4) Conclusion: The intervention of garlic is beneficial to control blood glucose and blood lipids in humans.
Topics: Garlic; Humans; Blood Glucose; Randomized Controlled Trials as Topic; Lipids; Glycated Hemoglobin; Dietary Supplements; Triglycerides; Female; Male; Cholesterol, HDL; Middle Aged; Adult
PubMed: 38892625
DOI: 10.3390/nu16111692 -
Nutrients May 2024Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the... (Meta-Analysis)
Meta-Analysis Review
Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials ( = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.
Topics: Diabetes Mellitus, Type 1; Humans; Gastrointestinal Microbiome; Randomized Controlled Trials as Topic; Glycated Hemoglobin; Probiotics; Prebiotics; Biomarkers; Synbiotics; Dietary Supplements; Female; Dysbiosis; Adult; Male
PubMed: 38892608
DOI: 10.3390/nu16111675 -
International Journal of Molecular... Jun 2024Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in... (Meta-Analysis)
Meta-Analysis Review
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1β, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.
Topics: Reperfusion Injury; Animals; Interleukin-10; Humans; Immunotherapy; Kidney; Acute Kidney Injury; Mice
PubMed: 38892418
DOI: 10.3390/ijms25116231 -
International Journal of Molecular... May 2024Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and... (Review)
Review
Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and distant metastasis is high. Differential diagnosis with squamous cell carcinoma is difficult, although NUT expression and YAP1 fusion products can be very useful for diagnosis. Currently, wide local excision is the main surgical treatment, although Mohs micrographic surgery is promising. To date, there is no consensus regarding the role of sentinel lymph node biopsy and consequential lymph node dissection. No guidelines exist for radiotherapy, which is mostly performed based on tumor characteristics and excision margins. Only a few studies report systemic treatment for advanced PC, although therapy with pembrolizumab and EGFR inhibitors show promise. In this review, we discuss epidemiology, clinical features, histopathological features, immunohistochemistry and fusion products, surgical management and survival outcomes according to stage, surgical management, radiotherapy and systemic therapy.
Topics: Humans; Eccrine Porocarcinoma; Immunohistochemistry; Sweat Gland Neoplasms; Biomarkers, Tumor; YAP-Signaling Proteins
PubMed: 38891945
DOI: 10.3390/ijms25115760 -
Immunity, Inflammation and Disease Jun 2024The identification of novel, easily measurable disease biomarkers might enhance the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The identification of novel, easily measurable disease biomarkers might enhance the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of ischemia-modified albumin (IMA), a marker of oxidative stress, acidosis, and ischemia, in RD patients and healthy controls.
METHODS
We searched PubMed, Web of Science, and Scopus from inception to January 15, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively.
RESULTS
In 20 studies investigating a total of 1188 RD patients (mean age 45 years, 64% females) and 981 healthy controls (mean age 44 years, 66% females), RD patients had significantly higher IMA concentrations when compared to controls (standard mean difference, SMD = 0.50, 95% CI: 0.18-0.83, p = .003; I = 92.4%, p < .001; low certainty of evidence). In subgroup analysis, the pooled SMD was significantly different in studies investigating ankylosing spondylitis (p < .001), Behçet's disease (p < .001), and rheumatoid arthritis (p = .033), but not familial Mediterranean fever (p = .48). Further associations were observed between the pooled SMD and the broad classification of autoimmune and/or autoinflammatory diseases, the study country, and the method used to measure IMA.
CONCLUSION
Our study suggests that IMA is a promising biomarker of oxidative stress, acidosis, and ischemia, as it can effectively discriminate between patients with different types of RDs and healthy controls. Our results warrant confirmation in longitudinal studies of patients with different types of RDs and different ethnicities (PROSPERO registration number: CRD42024509126).
Topics: Humans; Rheumatic Diseases; Biomarkers; Serum Albumin, Human; Oxidative Stress; Female; Ischemia; Male; Middle Aged
PubMed: 38888377
DOI: 10.1002/iid3.1324