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Cureus May 2024Dry eye disease frequently manifests following corneal refractive procedures, significantly impacting patients' quality of life. This review systematically synthesizes... (Review)
Review
Dry eye disease frequently manifests following corneal refractive procedures, significantly impacting patients' quality of life. This review systematically synthesizes current evidence on the pathophysiological mechanisms, risk factors, and therapeutic interventions for post-refractive surgery dry eye. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of literature published until August 2023 was conducted, focusing on post-refractive surgery dry eye. Eighteen relevant studies were identified through screening and eligibility assessment. A qualitative synthesis of outcomes was performed using narrative and thematic analysis methods. Surgically induced neurotrophic deficiency, stemming from nerve transection, triggers a cascade of events including apoptosis, inflammation, and lacrimal dysfunction, ultimately leading to tear film instability. Risk factors such as female gender, thyroid eye disease, meibomian gland dysfunction, higher ablation depths, and the use of LASIK over surface ablation exacerbate the condition. While conventional treatments like artificial tears provide temporary relief, emerging interventions such as nerve growth factors, matrix metalloproteinase inhibitors, serum eye drops, and specialized contact lenses show promise in promoting nerve regeneration and epithelial healing. Strategies such as customized ablation profiles, smaller optical zones, and nerve-sparing techniques like small incision lenticule extraction demonstrate potential advantages. A multifaceted therapeutic approach targeting neuroprotection, anti-inflammatory mechanisms, and tear film stabilization is imperative for effectively managing post-refractive surgery dry eye. Future research should focus on evaluating prognostic biomarkers, exploring precision medicine approaches, and investigating neuroprotective adjuvants to further enhance treatment outcomes.
PubMed: 38916023
DOI: 10.7759/cureus.61004 -
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 -
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 -
Kidney International Reports Jun 2024Chronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of chronic kidney disease (CKD) affecting young individuals mostly in...
INTRODUCTION
Chronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of chronic kidney disease (CKD) affecting young individuals mostly in agricultural communities in Central America and South Asia. CKDu is a diagnosis of exclusion made in individuals from endemic regions.
METHODS
We conducted a systematic review of the primary literature on urinary and plasma kidney injury biomarkers measured in the setting of CKDu (through February 2023). The literature was identified via a Web of Science search and hand search of the references of previously identified literature. Search terms included "CKDu," "Mesoamerican Nephropathy," "CKD of unknown etiology," "Chronic Interstitial Nephritis in Agricultural Communities," "biomarker," "urin∗," and/or "plasma."
RESULTS
A total of 25 papers were included. The 2 most frequently measured biomarkers were urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL). There was substantial variability in study design, laboratory assay methods, and statistical methodology, which prohibited meta-analysis.
CONCLUSION
Biomarkers that identify tubulointerstitial disease early and accurately may substantially accelerate progress in the study of CKDu and facilitate public health approaches that eventually lead to its prevention and elimination. To date, the literature is limited by relatively small sample sizes and methodological limitations which should be addressed in future studies.
PubMed: 38899184
DOI: 10.1016/j.ekir.2024.03.013 -
European Urology Focus Jun 2024Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited... (Review)
Review
BACKGROUND AND OBJECTIVE
Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one.
METHODS
The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703.
KEY FINDINGS AND LIMITATIONS
Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR.
CONCLUSIONS AND CLINICAL IMPLICATIONS
DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies.
PATIENT SUMMARY
In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.
PubMed: 38897871
DOI: 10.1016/j.euf.2024.05.024 -
Cancers May 2024The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. (Review)
Review
BACKGROUND
The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas.
METHODOLOGY
The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction.
RESULTS
Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion.
CONCLUSION
Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.
PubMed: 38893207
DOI: 10.3390/cancers16112089 -
Journal of Clinical Medicine May 2024It is unclear whether other cardiac biomarkers than NT-proBNP can be useful in the risk stratification of patients weaning from mechanical ventilation. The aim of this... (Review)
Review
It is unclear whether other cardiac biomarkers than NT-proBNP can be useful in the risk stratification of patients weaning from mechanical ventilation. The aim of this study is to summarize the role of ischemic cardiac biomarkers in predicting spontaneous breathing trial (SBT) or extubation failure. : We systematically searched Embase, MEDLINE, Web of Science, and Cochrane Central for studies published before January 2024 that reported the association between ischemic cardiac biomarkers and SBT or extubation failure. Data were extracted using a standardized form and methodological assessment was performed using the QUIPS tool. Seven observational studies investigating four ischemic cardiac biomarkers (Troponin-T, Troponin-I, CK-MB, Myoglobin) were included. One study reported a higher peak Troponin-I in patients with extubation failure compared to extubation success (50 ng/L [IQR, 20-215] versus 30 ng/L [IQR, 10-86], = 0.01). A second study found that Troponin-I measured before the SBT was higher in patients with SBT failure in comparison to patients with SBT success (100 ± 80 ng/L versus 70 ± 130 ng/L, = 0.03). A third study reported a higher CK-MB measured at the end of the SBT in patients with weaning failure (SBT or extubation failure) in comparison to weaning success (8.77 ± 20.5 ng/mL versus 1.52 ± 1.42 ng/mL, = 0.047). Troponin-T and Myoglobin as well as Troponin-I and CK-MB measured at other time points were not found to be related to SBT or extubation failure. However, most studies were underpowered and with high risk of bias. : The association with SBT or extubation failure is limited for Troponin-I and CK-MB and appears absent for Troponin-T and Myoglobin, but available studies are hampered by significant methodological drawbacks. To more definitively determine the role of ischemic cardiac biomarkers, future studies should prioritize larger sample sizes, including patients at risk of cardiac disease, using stringent SBTs and structured timing of laboratory measurements before and after SBT.
PubMed: 38892952
DOI: 10.3390/jcm13113242 -
Journal of Clinical Medicine May 2024Asthma is a chronic inflammatory airway disease characterized by recurrent symptoms in response to a wide range of external stimuli, including allergens, viral... (Review)
Review
Asthma is a chronic inflammatory airway disease characterized by recurrent symptoms in response to a wide range of external stimuli, including allergens, viral infections, and air pollution together with internal host-derived danger signals. The disease is traditionally associated with adaptive immune responses; recent research emphasizes the critical role of innate immunity in its pathogenesis. The complement system, activated as part of the defense mechanisms, plays a crucial role in bridging innate to adaptive immunity. While experimental models demonstrate complement cascade activation in asthma, human studies remain limited. This systematic review summarizes existing literature on the complement system in asthma patients, gathering data from PubMed, Web of Science, Scopus, and Google Scholar. The protocol was registered in the OSF. Out of 482 initially identified articles, only 24 met the eligibility criteria, revealing disparities in sample origin, methodologies, and populations. Despite observed heterogeneity, a consistent result was found in the elevation of complement regulatory proteins, such as complement Factor H, in samples from patients with asthma compared to those from healthy subjects. The increased level of regulatory proteins, such as Factor H and I highlight that these may influence asthma pathophysiology. The role of complement factors as potential biomarkers of asthma activity and severity needs further evaluation.
PubMed: 38892755
DOI: 10.3390/jcm13113044 -
Nutrients May 2024Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting.
OBJECTIVE
Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases.
DATA SOURCES
A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction.
DATA ANALYSIS
It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion.
CONCLUSIONS
The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.
Topics: Irritable Bowel Syndrome; Humans; Feces; Fatty Acids, Volatile; Fecal Microbiota Transplantation; Probiotics; Propionates; Randomized Controlled Trials as Topic; Acetates; Female; Gastrointestinal Microbiome; Biomarkers; Male; Adult; Case-Control Studies
PubMed: 38892659
DOI: 10.3390/nu16111727 -
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