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Gaceta Medica de Mexico 2016Biomarkers are a subcategory of clinical signs that can be measured and reproduced with precision and influence to predict outcome. Tissue, cells, and fluid conform the... (Review)
Review
BACKGROUND
Biomarkers are a subcategory of clinical signs that can be measured and reproduced with precision and influence to predict outcome. Tissue, cells, and fluid conform the biological process. Biomarker usefulness is to determine and specify illness predisposition counting with variability and validity. Process systematization can reduce operative costs. To date, four major biomarkers have been described for high-grade gliomas: 1p/19q deletion, O6-methylguanine-DNA methyltransferase (MGMT) promoter mutation, IDH1/IDH2 mutation, and microRNA. In this manuscript we present a systematic review according to the MOOSE protocol to establish the bases to describe the utility of biomarkers in high-grade tumors.
MATERIALS AND METHODS
We conducted a systematic review of the literature according to the PRISMA and MOOSE guides of all the published data from January 2004 to November 2014 with the key words: "biological markers" and "glioblastoma" that included OR and 95% CI. One researcher performed data extraction and analysis.
RESULTS
A total of 169 articles were found in three major medical search engines: PubMed (42), Embase (30) and Ovid (96).
CONCLUSION
Biomarkers are tools designed for early detection of specific illnesses such as high-grade glioma. Lack of methodological standardization slows down the speed of progress.
Topics: Genetic Markers; Glioma; Humans; Neoplasm Grading
PubMed: 26927648
DOI: No ID Found -
Neurogenetics Oct 2022C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic review aims to... (Review)
Review
C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic review aims to identify case reports with genetic variants in CTBP1 and CTBP2 associated with brain development syndromes.We screened different databases (PubMed, Scopus, Google Scholar, LILACS) by systematically searching journals and checking reference lists and citations of background papers. We found fourteen cases (10 males) from five papers carrying two pathogenic, heterozygous variants in the CTBP1 gene (13 individuals carried the missense mutation c.991C T, p.Arg342Trp, and one subject carrying the 2-base pair deletion c.1315_1316delCA, p.Gln439ValfsTer84). These mutations were de novo in 13 cases and one case of maternal germinal mosaicism. Two variants are in the same domain of the protein: Pro-Leu-Asp-Leu-Ser (PLDLS) C terminal. Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss. We did not identify reported cases associated with homozygous mutations harbored in CTBP1. We did not identify any report of neurodevelopment phenotypes associated with heterozygous or homozygous CTBP2 mutations. Due to CTBP2/RIBEYE being a gene with dual function, identifying and interpreting the potential pathogenic variants is challenging.Further, homozygous mutations in the CTBP2 gene may be lethal. The mechanisms involved in the pathogenesis of neurodevelopment due to variants of these proteins have not yet been elucidated, despite some functional evidence. Further studies should be conducted to understand these transcription factors and their interaction with each other and their partners.
Topics: Humans; Alcohol Oxidoreductases; Ataxia; Co-Repressor Proteins; Muscle Hypotonia; Mutation; Mutation, Missense; Transcription Factors
PubMed: 36331689
DOI: 10.1007/s10048-022-00700-w -
Cureus Sep 2022A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently... (Review)
Review
A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently discovered. Its approval by the Food and Drug Administration (FDA) in 2019 has expanded the target therapy group to individuals aged twelve and up with at least one Phe508del (phenylalanine 508 deletion) mutation in the CFTR gene. This systematic review aims to assess this combination therapy's safety and efficacy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, an in-depth search was performed. The search was done by utilizing databases such as PubMed Central (PMC), Google Scholar, and Science Direct for articles related to this topic. Studies published in the last five years in the English language were chosen preliminarily. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias and finalize ten articles to be used in this review. The chosen articles constituted four randomized control trials (RCTs), four systematic reviews, and two narrative reviews. The last date for data collection was April 24, 2022. Based on the findings of this review, we concluded that by combining three CFTR modulators, this therapy had outperformed all the currently available medications in terms of improving pulmonary function, reducing exacerbations, and enhancing the quality of life of CF patients. In clinical trials, headache and rash were the most common side effects, and laboratory testing to assess liver function is suggested. Long-term safety and effectiveness must be confirmed by the continued review of real-life patient data. Studies done on triple therapy thus far have been promising. Unfortunately, a small proportion of the CF population remains ineligible for any form of CFTR modulator therapy owing to their type of genetic mutation, and this provides ground for further research in this field.
PubMed: 36284811
DOI: 10.7759/cureus.29359 -
Frontiers in Immunology 2022Duvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.
BACKGROUND
Duvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies support the efficacy of duvelisib, the safety of duvelisib remains with great attention. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid neoplasm types.
METHODS
We searched prospective clinical trials from PUBMED, EMBASE, Cochrane Library, and ClinicalTrials.gov. For efficacy analysis, Overall response rate (ORR), complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), rate of progressive disease (PDR), median progression-free survival (mPFS), 12-/24-month PFS, and 12-month overall survival (OS) were assessed. For safety analysis, the incidences of any grade and grade ≥3 adverse events (AEs), serious AEs, and treatment-related discontinuation and death were evaluated. Subgroup analysis based on the disease type was performed.
RESULTS
We included 11 studies and 683 patients, including 305 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 187 B-cell indolent non-Hodgkin lymphoma (iNHL), 39 B-cell aggressive non-Hodgkin lymphoma (aNHL), and 152 T-cell non-Hodgkin lymphoma (T-NHL) patients. The pooled ORR in CLL/SLL, iNHL, aNHL and T-NHL was 70%, 70%, 28% and 47%, respectively. Additionally, the pooled ORR in CLL/SLL patients with or without TP53 mutation/17p-deletion (62% vs. 74%, p=0.45) and in follicular lymphoma (FL) or other iNHL (69% vs. 57%, p=0.38) had no significant differences. Mantle cell lymphoma (MCL) patients had higher pooled ORR than other aNHL (68% vs. 17%, p=0.04). Angioimmunoblastic TCL (AITL) patients had higher pooled ORR than other PTCL patients (67% vs. 42%, p=0.01). The pooled incidence of any grade, grade ≥3, serious AEs, treatment-related discontinuation and death was 99%, 79%, 63%, 33% and 3%, respectively. The most frequent any-grade AEs were diarrhea (47%), ALT/AST increase (39%), and neutropenia (38%). The most frequent grade ≥3 AEs were neutropenia (25%), ALT/AST increased (16%), diarrhea (12%), and anemia (12%).
CONCLUSION
Generally, duvelisib could offer favorable efficacy in patients with RR CLL/SLL, iNHL, MCL, and AITL. Risk and severity in duvelisib treatment may be mitigated through proper identification and management.
Topics: Humans; Adult; Phosphatidylinositol 3-Kinases; Leukemia, Lymphocytic, Chronic, B-Cell; Prospective Studies; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Lymphoma, B-Cell; Neutropenia; Diarrhea
PubMed: 36685572
DOI: 10.3389/fimmu.2022.1070660 -
Oncotarget Jun 2017A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.
BACKGROUND
A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue.
RESULTS
In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS.
MATERIALS AND METHODS
10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS.
CONCLUSIONS
In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.
Topics: Bcl-2-Like Protein 11; Disease-Free Survival; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Mutation; Polymorphism, Genetic; Treatment Outcome
PubMed: 28467813
DOI: 10.18632/oncotarget.17102 -
Mutation Research. Reviews in Mutation... 2016The correlation of Y-chromosome b2/b3 partial deletions with spermatogenic failure remains dubious. We undertook a systematic review of the literature followed by... (Meta-Analysis)
Meta-Analysis Review
The correlation of Y-chromosome b2/b3 partial deletions with spermatogenic failure remains dubious. We undertook a systematic review of the literature followed by meta-analyses and trial sequential analyses in order to compare the frequency of b2/b3 deletions between oligo/azoospermic infertile and normozoospermicmen. Out of twenty-four studies reviewed for meta-analysis, twenty reported no correlation between this deletion and male infertility and two studies each reported a direct and inverse correlation. In the collective analysis, 241 out of 8892 (2.71%) oligo/azoospermic individuals and 118 out of 5842 (2.02%) normozoospermic controls had a b2/b3 deletion, suggesting a relatively higher frequency of deletions in the cases. Eventually, meta-analysis showed a significant correlation between b2/b3 deletions and the risk of spermatogenic loss/infertility (Fixed model: OR=1.313, 95% CI=1.04-1.65, p=0.02; Random model: OR=1.315, 95% CI=1.02-1.70, p=0.037). Further meta-analysis on studies grouped by ethnicity and geographic regions showed that the b2/b3 deletions are significantly associated with spermatogenic loss/infertility in Mongolians, Nigro-Caucasians, East Asians and Africans, but not in Caucasians, Europeans, South Asians and Dravidians. In summary, the Y-chromosome b2/b3 deletions increase infertility risk; however, it may be significant only in the Mongolian populations and the East Asian region.
Topics: Case-Control Studies; Chromosome Deletion; Chromosomes, Human, Y; Ethnicity; Humans; Infertility, Male; Male; Odds Ratio; Prevalence; Publication Bias; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development; Spermatogenesis
PubMed: 27234565
DOI: 10.1016/j.mrrev.2016.04.007 -
Journal of Magnetic Resonance Imaging :... Nov 2023As an important genomic marker for oligodendrogliomas, early determination of 1p/19q co-deletion status is critical for guiding therapy and predicting prognosis in... (Review)
Review
As an important genomic marker for oligodendrogliomas, early determination of 1p/19q co-deletion status is critical for guiding therapy and predicting prognosis in patients with glioma. The purpose of this study is to systematically review the literature concerning the magnetic resonance imaging (MRI) with artificial intelligence (AI) methods for predicting 1p/19q co-deletion status in glioma. PubMed, Scopus, Embase, and IEEE Xplore were searched in accordance with the Preferred Reporting Items for systematic reviews and meta-analyses guidelines. Methodological quality of studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2. Finally, 28 studies were included in the quantitative analysis. Diagnostic test accuracy reached an area under the ROC curve of 0.71-0.98 were reported in 24 studies. The remaining four studies with no available AUC provided an accuracy of 0.75-0. 89. The included studies varied widely in terms of imaging sequences, input features, and modeling methods. The current review highlighted that integrating MRI with AI technology is a potential tool for determination 1p/19q status pre-operatively and noninvasively, which can possibly help clinical decision-making. However, the reliability and feasibility of this approach still need to be further validated and improved in a real clinical setting. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 2.
Topics: Humans; Artificial Intelligence; Brain Neoplasms; Reproducibility of Results; Chromosome Deletion; Glioma; Isocitrate Dehydrogenase; Oligodendroglioma; Mutation
PubMed: 37083159
DOI: 10.1002/jmri.28737 -
Fertility and Sterility Jan 2024To investigate whether Azoospermia Factor c (AZFc) microdeletions affect Assisted Reproductive Technology (ART) outcomes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate whether Azoospermia Factor c (AZFc) microdeletions affect Assisted Reproductive Technology (ART) outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENTS
Infertile men with and without AZFc microdeletions.
INTERVENTION(S)
Electronic databases were searched for case-control studies reporting sperm retrieval rates and outcomes of ART in infertile men with and without AZFc microdeletions from inception to April 2023. Study quality was assessed using the Newcastle-Ottawa Scale. Summary effect sizes (odds ratio [OR] with 95% confidence interval [CI]) were calculated for both categories of infertile men.
MAIN OUTCOME MEASURES
The primary outcome was successful sperm retrieval and the secondary outcomes were outcomes of ART.
RESULTS
Case-control studies reporting sperm retrieval rates and ART outcomes in men with AZFa and AZFb deletions were unavailable. On the basis of the data from 3,807 men, sperm retrieval rates were found to be higher in men with AZFc microdeletions compared to their non-deleted counterparts [OR = 1.82, 95% CI 0.97, 3.41], but the difference was not statistically significant. A significantly lower fertilization rate (OR = 0.61, 95% CI [0.50, 0.74]), clinical pregnancy rate (OR = 0.61, 95% CI [0.42, 0.89]), and live birth rate (OR = 0.54, 95% CI [0.40, 0.72]) were observed in men with AZFc deletions compared with men without deletions. There was no statistically significant difference in rates of embryo cleavage, blastocyst formation, good-quality embryos, implantation, and miscarriage between the two groups. On correcting for female factors, the fertilization rate (OR = 0.76, 95% CI [0.71, 0.82]), cleavage rate (OR = 0.54, 95% CI [0.41, 0.72]), clinical pregnancy rate (OR = 0.39, 95% CI [0.30, 0.52]), and live birth rate (OR = 0.48, 95% CI [0.35, 0.65]) were significantly lower in men with AZFc deletions compared with controls.
CONCLUSIONS
Presence of AZFc microdeletions adversely affects outcomes of ART in infertile men. Further in-depth studies delineating the role of the AZF genes in embryonic development are necessary to understand the full-impact of this finding.
CLINICAL TRIAL REGISTRATION NUMBER
CRD42022311738.
Topics: Pregnancy; Humans; Male; Female; Azoospermia; Oligospermia; Retrospective Studies; Chromosome Deletion; Chromosomes, Human, Y; Semen; Infertility, Male; Sertoli Cell-Only Syndrome
PubMed: 37923163
DOI: 10.1016/j.fertnstert.2023.10.029 -
Journal of Oncology 2022To compare the efficacy of EGFR-TKIs combined with antiangiogenic agents between non-small cell lung cancer patients with exon 19 deletion and patients with exon 21...
Comparison of the Efficacy of EGFR-TKIs Combined with Antiangiogenic Agents between Patients with Exon 19 Deletion and Patients with Exon 21 Leu858 Arg Mutation: A Systematic Review and Meta-Analysis.
PURPOSE
To compare the efficacy of EGFR-TKIs combined with antiangiogenic agents between non-small cell lung cancer patients with exon 19 deletion and patients with exon 21 Leu858 Arg mutation.
METHODS
Electronic databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched for studies published until March 2022. Randomized control trials comparing the survival of EGFR-TKIs plus antiangiogenic agents with EGFR-TKI were extracted. The primary endpoint was progression-free survival (PFS).
RESULTS
Five randomized control trials involving 1533 patients were as follows: 818 patients had exon 19 deletion, and 715 patients with exon 21 Leu858 Arg mutation. The methodological quality of the 5 randomized control trials was high. EGFR-TKIs plus antiangiogenic agents improved PFS in patients with exon 19 deletion (hazard ratio [HR] = 0.62, 95% confidence interval [CI]: 0.51-0.75) and exon 21 Leu858 Arg mutation (HR = 0.61, 95% CI: 0.50-0.75). PFS did not differ between the exon 19 deletion and exon 21 Leu858 Arg mutation groups ( = 0.07, =0.94).
CONCLUSIONS
PFS was comparable between patients receiving EGFR-TKIs combined with antiangiogenic agents with exon 19 deletion and those with exon 21 Leu858 Arg mutation.
PubMed: 36312218
DOI: 10.1155/2022/9399797 -
American Journal of Reproductive... Dec 2020Insufficient response to oxidative stress in placenta is proposed as a contributing factor for preeclampsia (PE) development. Glutathione S-transferases (GST) have... (Meta-Analysis)
Meta-Analysis Review
Insufficient response to oxidative stress in placenta is proposed as a contributing factor for preeclampsia (PE) development. Glutathione S-transferases (GST) have significant role in detoxification processes. Conflicting results were published by several research groups regarding GST T1 and GST M1 deletion polymorphism as risk factors for PE. The aim of the present meta-analysis was to get a better understanding of the impact of these polymorphisms in preeclampsia development. To identify relevant case-control studies, the author team searched Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, major subject journals, and gray literature. Pooled odds ratios and 95% confidence intervals for GST M1 and GST T1 deletion polymorphism and preeclampsia were derived from random effects models. This meta-analysis included 10 eligible studies. The pooled analyses showed no association between GST M1/GST T1 deletion polymorphisms and susceptibility to PE. Even though high heterogeneity was founded among results for GST M1 and double null genotypes, Egger's and Begg's tests (0.17 and 0.18, respectively) revealed no statistical evidence of publication bias among included studies. The present updated systematic review and meta-analysis found no association between GST M1 and GST T1 deletion polymorphism and PE risk.
Topics: Female; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Risk; Sequence Deletion
PubMed: 32658338
DOI: 10.1111/aji.13303