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JCO Precision Oncology Aug 2022Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified... (Meta-Analysis)
Meta-Analysis
PURPOSE
Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.
METHODS
We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival.
RESULTS
A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors.
CONCLUSION
This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.
Topics: Humans; Lung Neoplasms; Melanoma; Mitogen-Activated Protein Kinases; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; United States
PubMed: 35977349
DOI: 10.1200/PO.22.00107 -
The Malaysian Journal of Medical... Jun 2022The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through... (Review)
Review
The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through insulin resistance. Glucose levels are related to AMPK subunit α2 encoded by . This systematic review and meta-analysis aimed to analyse the association between variation and T2DM risk. Publication search related to and T2DM used PubMed, ProQuest, and ScienceDirect databases. Article selection based on inclusion and exclusion criteria only included Japanese and Chinese populations. This meta-analysis used five genotype models to estimate the effect of variation and T2DM risk. Additionally, a fixed-effect model was selected to measure the pooled size effect if > 0.05 or I < 50%. Qualitative analysis included four eligible studies, and meta-analysis included only two studies because both showed data concerning rs2746342 variation. Patients with G allele are 1.45 times more likely to have T2DM than patients with T allele (95% confidence interval [CI]: 1.20, 1.76; : 0.0001). Notably, patients who had GG genotype have 1.96 times higher risk of T2DM compared with those with TT genotype (95% CI: 1.34, 2.87; : 0.0005), dominant model (odds ratio [OR]: 1.75; 95% CI: 1.32, 2.31; : 0.001), and recessive model (OR: 1.43; 95% CI: 1.01, 2.01; : 0.04). variation, especially in rs2746342, has an association with T2DM risk in the G allele, additive, dominant, and recessive models. G allele might be the most contributable factor in increasing T2DM susceptibility.
PubMed: 35846493
DOI: 10.21315/mjms2022.29.3.2 -
Expert Review of Vaccines Sep 2022A number of vaccines have now been developed against COVID-19. Differences in reactogenicity and safety profiles according to the vaccine technologies employed are... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
A number of vaccines have now been developed against COVID-19. Differences in reactogenicity and safety profiles according to the vaccine technologies employed are becoming apparent from clinical trials.
METHODS
Five databases (Medline, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, London School of Hygiene and Tropical Medicine COVID-19 vaccine tracker) were searched for relevant randomized controlled trials between 1 January 2020 and 12 January 2022 according to predetermined criteria with no language limitations.
RESULTS
Forty-two datasets were identified, with 20 vaccines using four different technologies (viral vector, inactivated, mRNA and protein sub-unit). Adults and adolescents over 12 years were included. Control groups used saline placebos, adjuvants, and comparator vaccines. The most consistently reported solicited adverse events were fever, fatigue, headache, pain at injection site, redness, and swelling. Both doses of mRNA vaccines, the second dose of protein subunit and the first dose of adenovirus vectored vaccines were the most reactogenic, while the inactivated vaccines were the least reactogenic.
CONCLUSIONS
The different COVID-19 vaccines currently available appear to have distinct reactogenicity profiles, dependent on the vaccine technology employed. Awareness of these differences may allow targeted recommendations for specific populations. Greater standardization of methods for adverse event reporting will aid future research in this field.
Topics: Adjuvants, Immunologic; Adolescent; Adult; COVID-19; COVID-19 Vaccines; Humans; Vaccines, Inactivated
PubMed: 35796029
DOI: 10.1080/14760584.2022.2098719 -
International Immunopharmacology Aug 2022High speed of COVID-19 vaccination has raised some concerns about the safety of the new vaccines. It is of a great importance to perform a review of the safety and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High speed of COVID-19 vaccination has raised some concerns about the safety of the new vaccines. It is of a great importance to perform a review of the safety and efficacy of the COVID-19 vaccines.
METHODS
Two International electronic databases (PubMed, ISI) were searched for clinical trials reporting efficacy and safety of COVID-19 vaccines compared to control group. Pooled risk ratio (RR) for total, systemic and local adverse events following immunization was calculated for different vaccine modalities.
RESULTS
The pooled RRs of total adverse reactions for Inactivated, mRNA, and vector vaccines were 1.46 (95% CI: 1.19-1.78), 2.01 (95% CI: 1.82 - 2.23), and 1.65 (95% CI: 1.31 - 2.32) respectively. The pooled RR for occurrence of systemic adverse reactions following immunization for different vaccine modalities was 1.13 (95% CI: 0.79 - 1.61), 1.53 (95% CI 1.08 - 2.16), 1.58 (95% CI: 1.13 - 1.90), 0.72 (95% CI: 0.34 - 1.55), and 1.62 (95% CI: 1.39 - 1.89) for inactivated vaccine, mRNA, vector, DNA, and protein subunit vaccines respectively. The pooled RR of local adverse event following immunization with inactivated vaccine, mRNA vaccine, vector vaccine, DNA vaccine, and protein subunit vaccine was 2.18 (95% CI: 1.32 - 3.59), 4.96 (95% CI: 4.02 - 6.11), 1.48 (95% CI: 0.88-2.50) 1.04 (95% CI: 0.12-8.75), and 4.09 (95% CI: 2.63-6.35) respectively.
CONCLUSION
mRNA vaccines are associated with greater risk of adverse events following immunization. However, at the present moment the benefits of all types of vaccines approved by WHO, still outweigh the risks of them and vaccination if available, is highly recommended.
Topics: COVID-19; COVID-19 Vaccines; Humans; Protein Subunits; RNA, Messenger; Vaccination; Vaccines, Inactivated; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35671640
DOI: 10.1016/j.intimp.2022.108906 -
Environmental Science and Pollution... Jun 2022As well as a lead-related environmental factor, genetic factors could also corroborate important changes in intelligence quotient (IQ) through single-nucleotide...
As well as a lead-related environmental factor, genetic factors could also corroborate important changes in intelligence quotient (IQ) through single-nucleotide polymorphisms. Thus, a systematic review was carried out to evaluate the possible influence of polymorphism on blood Pb levels and IQ points in pediatric patients (0-19 years old). Following the PRISMA guideline, the studies were systematically collected on PubMed, Scopus, and Embase databases. Six genes (transferrin (TF); glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A); glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B); dopamine receptor D2/ankyrin repeat and kinase domain containing 1 ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1); aminolevulinate dehydratase (ALAD); vitamin D receptor (VDR)) were found in six selected articles. In these genes, 11 single-nucleotide polymorphisms were searched and six different types of variations (missense variant, intron variant, synonymous variant, stop, stop gained) were observed. Due to the few studies in the literature, there is no conclusive data to point out that there is a direct relationship between polymorphisms, Pb levels, and reduction of IQ points.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Young Adult; Genotype; Glutamates; Lead; N-Methylaspartate; Nucleotides; Polymorphism, Single Nucleotide; Protein Serine-Threonine Kinases
PubMed: 35386084
DOI: 10.1007/s11356-022-19981-7 -
PloS One 2022COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. (Meta-Analysis)
Meta-Analysis
BACKGROUND
COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed.
METHODS AND FINDINGS
Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, -5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events.
CONCLUSIONS
The evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines.
Topics: COVID-19; COVID-19 Vaccines; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; SARS-CoV-2; Survival Analysis; Treatment Outcome; Vaccine Efficacy; Vaccines, Inactivated; Vaccines, Subunit; mRNA Vaccines
PubMed: 35061702
DOI: 10.1371/journal.pone.0260733 -
Bone Feb 2022Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in...
BACKGROUND
Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in the guanine nucleotide-binding protein gene (GNAS). In order to better understand this disease, several animal models have been developed with different strategies and features.
OBJECTIVE
Conduct a systematic review to analyze and compare animal models with the causative mutation and features of FD.
METHODS
A PRISMA search was conducted in Scopus, PubMed, and Web of Science. Studies reporting an in vivo model of FD that expressed the causative mutation were included for analysis. Models without the causative mutation, but developed an FD phenotype and models of FD cell implantation were included for subanalysis.
RESULTS
Seven unique models were identified. The models were assessed and compared for their face validity, construct validity, mosaicism, and induction methods. This was based on the features of clinical FD that were reported within the categories of: macroscopic features, imaging, histology and histomorphometry, histochemical and cellular markers, and blood/urine markers.
LIMITATIONS
None of the models reported all features of FD and some features were only reported in one model. This made comparing models a challenge, but indicates areas where further research is necessary.
CONCLUSION
The benefits and disadvantages of every model were assessed from a practical and scientific standpoint. While all published reports lacked complete data, the models have nonetheless informed our understanding of FD and provided meaningful information to guide researchers in bench and clinical research.
Topics: Animals; Bone and Bones; Fibrous Dysplasia of Bone; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Mutation
PubMed: 34875396
DOI: 10.1016/j.bone.2021.116270 -
PloS One 2021Genetic association studies on alopecia areata (AA) performed in various populations have shown heterogeneous results. The aim of the current review was to synthesize... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Genetic association studies on alopecia areata (AA) performed in various populations have shown heterogeneous results. The aim of the current review was to synthesize the results of said studies to estimate the impact of FAS, FASL, PTPN22, CTLA4 and IL2RA gene polymorphisms on AA susceptibility.
DESIGN
A systematic literature search was conducted in the Medline, Web of Science, Scopus, EMBASE and LILACS databases. Studies published up to June 2020 were included. The results available in the grey literature including the Open Grey and Google Scholar databases were also used. The texts of potentially related studies were screened by individual reviewers. Evidence of publication bias was assessed using the Newcastle-Ottawa scale and the quality of evidence was assessed using the GRADE system. The quantitative synthesis was performed using the fixed effect model.
RESULTS
Out of 1784 articles, we identified 18 relevant articles for the qualitative synthesis and 16 for the quantitative synthesis. In a study of rs2476601 polymorphism of PTPN22 gene, including 1292 cases and 1832 controls, a correlation was found with the risk of developing AA in the allelic model (OR1.49 [95% C:1.13-1.95]), the heterozygous codominant (OR1.44 [95% CI:1:19-1.76]) and dominant model (OR1.43 [95% CI:1.18-1.73]). No association was found between the presence of FASL, PTPN22, CTLA and IL2RA gene polymorphisms with AA susceptibility.
CONCLUSIONS
The results suggest that the T allele of the single nucleoid polymorphism (SNP) rs2476601 in PTPN22 gene is a risk factor for developing alopecia areata. However, more robust studies defining the ethnic background of the population of origin are required, so that the risk identified in the present study can be validated. Additionally, a greater number of studies is necessary to evaluate the role of the FAS, FASL, PTPN22, CTLA4 and IL2RA genetic variants, given the heterogenous results found in the literature.
Topics: Alleles; Alopecia Areata; CTLA-4 Antigen; Fas Ligand Protein; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-2 Receptor alpha Subunit; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; fas Receptor
PubMed: 34735462
DOI: 10.1371/journal.pone.0258499 -
World Neurosurgery Jul 2022The goal of this study was to systematically review the usefulness of serum biomarkers in the setting of ischemic stroke (IS) to predict long-term outcome. (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The goal of this study was to systematically review the usefulness of serum biomarkers in the setting of ischemic stroke (IS) to predict long-term outcome.
METHODS
A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2018. All studies assessing long-term functional outcome (defined as ≥30 days) after IS with respect to serum biomarkers were included. Data were extracted and pooled using a meta-analysis of odds ratios.
RESULTS
Of the 2928 articles in the original literature search, 183 studies were selected. A total of 127 serum biomarkers were included. Biomarkers were grouped into several categories: inflammatory (n = 32), peptide/enzymatic (n = 30), oxidative/metabolic (n = 28), hormone/steroid based (n = 23), and hematologic/vascular (n = 14). The most commonly studied biomarkers in each category were found to be CRP, S100β, albumin, copeptin, and D-dimer. With the exception of S100β, all were found to be statistically associated with >30-day outcome after ischemic stroke.
CONCLUSIONS
Serum-based biomarkers have the potential to predict functional outcome in patients with IS. This meta-analysis has identified C-reactive protein, albumin, copeptin, and D-dimer to be significantly associated with long-term outcome after IS. These biomarkers have the potential to serve as a platform for prognosticating stroke outcomes after 30 days. These serum biomarkers, some of which are routinely ordered, can be combined with imaging biomarkers and used in artificial intelligence algorithms to provide refined predictive outcomes after injury. These tools will assist physicians in providing guidance to families regarding long-term independence of patients.
Topics: Artificial Intelligence; Biomarkers; Brain Ischemia; C-Reactive Protein; Humans; Ischemic Stroke; Prognosis; S100 Calcium Binding Protein beta Subunit
PubMed: 34728391
DOI: 10.1016/j.wneu.2021.10.157 -
Frontiers in Endocrinology 2021The CDK5 regulatory subunit-associated protein 1-like 1 () contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The CDK5 regulatory subunit-associated protein 1-like 1 () contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between polymorphisms rs7756992 A>G and rs7754840 C>G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.
MATERIALS AND METHODS
A meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied polymorphisms and GDM risk with the summary odds ratio (OR) and 95% confidence interval (CI). In addition, trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis were performed to confirm the study findings.
RESULTS
A total of 13,306 subjects were included in the present study. Meta-analysis results showed that the variant heterozygous and homozygous genotypes of the two polymorphisms were associated with increased GDM risk in comparison with the wild-type AA genotype (AG AA: OR = 1.23, 95% CI = 1.08, 1.41, = 0.002; GG AA: OR = 1.47, 95% CI = 1.05, 2.05, = 0.024 for rs7756992; and CG GG: OR = 1.36, 95% CI = 1.13, 1.65, = 0.002; CC GG: OR = 1.76, 95% CI = 1.37, 2.26, < 0.001 for rs7754840). The TSA confirmed a significant association between rs7754840 and the susceptibility to GDM because the cumulative Z-curve crossed both the conventional cutoff value and the TSA boundaries under the heterozygote and homozygote models.
CONCLUSIONS
This study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.
Topics: Case-Control Studies; Cyclin-Dependent Kinase 5; Diabetes, Gestational; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors; tRNA Methyltransferases
PubMed: 34721291
DOI: 10.3389/fendo.2021.722674