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PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
PloS One 2015The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to... (Review)
Review
Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.
BACKGROUND
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
METHODS
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
RESULTS
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
CONCLUSIONS
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
Topics: Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Meta-Analysis as Topic; Mutation; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 25816236
DOI: 10.1371/journal.pone.0120470 -
Clinical Microbiology and Infection :... Nov 2021The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to... (Review)
Review
BACKGROUND
The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance.
OBJECTIVES
This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB.
DATA SOURCES
Data source was PubMed.
STUDY ELIGIBILITY CRITERIA
Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains.
RESULTS
In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously.
CONCLUSIONS
Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.
Topics: DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae
PubMed: 34265461
DOI: 10.1016/j.cmi.2021.07.007 -
Drug Design, Development and Therapy 2021Various imidazole-containing compounds have been tested for their medical usefulness in clinical trials for several disease conditions. The rapid expansion of...
Various imidazole-containing compounds have been tested for their medical usefulness in clinical trials for several disease conditions. The rapid expansion of imidazole-based medicinal chemistry suggests the promising and potential therapeutic values of imidazole-derived compounds for treating incurable diseases. Imidazole core scaffold contains three carbon atoms, and two nitrogen with electronic-rich characteristics that are responsible for readily binding with a variety of enzymes, proteins, and receptors compared to the other heterocyclic rings. Herein, we provide a thorough overview of the current research status of imidazole-based compounds with a wide variety of biological activities including anti-cancer, anti-microbial, anti-inflammatory and their potential mechanisms including topoisomerase IIR catalytic inhibition, focal adhesion kinase (FAK) inhibition, c-MYC G-quadruplex DNA stabilization, and aurora kinase inhibition. Additionally, a great interest was reported in the discovery of novel imidazole compounds with anti-microbial properties that break DNA double-strand helix and inhibit protein kinase. Moreover, anti-inflammatory mechanisms of imidazole derivatives include inhibition of COX-2 enzyme, inhibit neutrophils degranulation, and generation of reactive oxygen species. This systemic review helps to design and discover more potent and efficacious imidazole compounds based on the reported derivatives, their ADME profiles, and bioavailability scores that together aid to advance this class of compounds.
Topics: Animals; Anti-Inflammatory Agents; Chemistry, Pharmaceutical; Humans; Imidazoles; Protein Kinase Inhibitors
PubMed: 34354342
DOI: 10.2147/DDDT.S307113 -
Sexually Transmitted Diseases May 2017Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the top 3 urgent threats to public health. Approaches to combat resistance include targeted... (Meta-Analysis)
Meta-Analysis Review
Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the top 3 urgent threats to public health. Approaches to combat resistance include targeted therapy with antibiotics previously thought to be ineffective, made possible by rapid molecular assays to predict susceptibility. Previous studies have associated the gyrase A (gyrA) gene of N. gonorrhoeae with in vitro resistance to ciprofloxacin. We conducted a systematic review of studies comparing N. gonorrhoeae gyrA genotype results with conventional antimicrobial susceptibility testing results. We identified 31 studies meeting inclusion criteria, among which 7 different loci for mutations in the gyrA gene were identified, from 16 countries between the years of 1996 and 2016. We then performed a meta-analysis among those studies stratifying by use of real-time polymerase chain reaction (PCR) or non-real-time PCR technique, and compared the summary receiver operating characteristic curves between the 2 PCR methods. Among studies using real-time PCR, the pooled estimate of sensitivity and specificity of gyrA genotype results for the prediction of N. gonorrhoeae susceptibility to ciprofloxacin were 98.2% (95% confidence interval [CI], 96.5-99.1%) and 98.6% (95% CI, 97.0-99.3%), respectively. The summary operating characteristic curves for studies using real-time PCR techniques were well separated from those using non-real-time PCR techniques, with only slight overlap in the CIs, suggesting that real-time PCR techniques were a more accurate approach. GyrA genotype testing is a novel approach to combating the emergence of multidrug-resistant N. gonorrhoeae and is a sensitive and specific method to predict in vitro ciprofloxacin susceptibility.
Topics: Anti-Bacterial Agents; Ciprofloxacin; DNA Gyrase; Drug Resistance, Bacterial; Genotype; Gonorrhea; Humans; Mutation; Neisseria gonorrhoeae; Polymerase Chain Reaction
PubMed: 28407640
DOI: 10.1097/OLQ.0000000000000591 -
Drug Discoveries & Therapeutics Nov 2020Diagnosis and management of hemophagocytic lymphohistiocytosis (HLH) in patients with human immunodeficiency virus (HIV) infection are scarcely described in the...
Diagnosis and management of hemophagocytic lymphohistiocytosis (HLH) in patients with human immunodeficiency virus (HIV) infection are scarcely described in the published literature. The aim of this systematic review was to delineate the triggers of HLH in patients with HIV and understand the role of steroids in the management. We conducted a comprehensive search of English medical literature via the Medline ⁄ PubMed database using different synonyms of "HIV" AND "HLH". The review was registered in PROSPERO (CRD42018099987). The titles and abstracts of the 185 articles between January 1986 and April 2018 were reviewed. The final analysis was done from 42 articles with 52 patients. HLH was associated with malignancy in 17 patients, while infection was found in 25 patients. No cause was identified in eight patients, out of which four had acute HIV infection. Death was reported in 21 patients. Presence of either malignancy (p = 0.051) or opportunistic infection (p = 0.69) was not associated with increased chances of death by univariate analysis. A total of 26 patients were treated with steroids, while etoposide was used in only four patients. Administration of steroids as a treatment of HLH was associated with more chances of death (p = 0.048). Malignancy and Opportunistic infections are important triggers for HLH in patients with HIV. Acute HIV by itself can act as a trigger for HLH. Evidence on the use of steroids as a treatment of HLH in patients with HIV is not convincing.
Topics: Adult; Anti-Retroviral Agents; Etoposide; Female; HIV; HIV Infections; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Neoplasms; Opportunistic Infections; Retrospective Studies; Steroids; Topoisomerase II Inhibitors
PubMed: 33116036
DOI: 10.5582/ddt.2020.03069