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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 -
International Journal of Molecular... May 2024Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid... (Meta-Analysis)
Meta-Analysis Review
The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.
Topics: Humans; Inflammatory Bowel Diseases; Psoriasis; Polymorphism, Single Nucleotide; Biological Products; Arthritis, Rheumatoid; Arthritis, Psoriatic; NLR Family, Pyrin Domain-Containing 3 Protein; Myeloid Differentiation Factor 88
PubMed: 38891983
DOI: 10.3390/ijms25115793 -
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 -
International Journal of Molecular... May 2024Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study... (Review)
Review
Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study aimed to identify and synthesize evidence of the relationship between glial dysfunction and suicidal behavior to understand the neurobiology of suicide. As of 26 January 2024, 46 articles that met the inclusion criteria were identified by searching PubMed and ISI Web of Science. Most postmortem studies, including 30 brain regions, have determined no density or number of total Nissl-glial cell changes in suicidal patients with major psychiatric disorders. There were 17 astrocytic, 14 microglial, and 9 oligodendroglial studies using specific markers of each glial cell and further on their specific gene expression. Those studies suggest that astrocytic and oligodendroglial cells lost but activated microglia in suicides with affective disorder, bipolar disorders, major depression disorders, or schizophrenia in comparison with non-suicided patients and non-psychiatric controls. Although the data from previous studies remain complex and cannot fully explain the effects of glial cell dysfunction related to suicidal behaviors, they provide risk directions potentially leading to suicide prevention.
Topics: Humans; Neuroglia; Suicide; Brain; Biomarkers; Autopsy; Suicidal Ideation; Bipolar Disorder
PubMed: 38891940
DOI: 10.3390/ijms25115750 -
International Journal of Molecular... May 2024The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a... (Meta-Analysis)
Meta-Analysis Review
The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing.
Topics: Humans; Heart Failure; Metabolomics; Biomarkers; Cardiovascular Diseases; Metabolome; Heart Disease Risk Factors
PubMed: 38891881
DOI: 10.3390/ijms25115693