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Frontiers in Endocrinology 2022It is currently controversial whether subclinical hyperthyroidism is associated with gene variants. We describe a man with subclinical hyperthyroidism and a gene...
BACKGROUND AND OBJECTIVES
It is currently controversial whether subclinical hyperthyroidism is associated with gene variants. We describe a man with subclinical hyperthyroidism and a gene variant who was diagnosed with Carney complex (CNC), and we performed a systematic review of published studies to assess the association between gene variants and the risk of subclinical hyperthyroidism.
DESIGN AND METHODS
The PubMed, EMBASE, OVID, Science Direct, and gray literature electronic databases were searched for articles published from January 2002 to May 2021 using predefined keywords and inclusion and exclusion criteria. Data on thyroid function from selected studies were extracted and analyzed.
RESULTS
We identified a CNC patient with a subclinical hyperthyroidism phenotype combined with multiple components and genetic sequenced data. In a subsequent systematic review, twenty selected studies (14 case studies and 6 series studies) enrolling 23 individuals were included in the final analysis. The patient's thyroid function data were qualitative in 11 cases and quantitative in 12 cases. The prevalence of subclinical hyperthyroidism in the CNC patients with a gene variant, including our patient, was markedly higher than that in the normal population (12.5% vs. 2%).
CONCLUSIONS
The findings of this systematic review provide helpful evidence that gene variants and subclinical hyperthyroidism are related and suggest that subclinical hyperthyroidism may be a neglected phenotype of gene variants and a novel component of CNC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021197655.
Topics: Carney Complex; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Humans; Hyperthyroidism; Phenotype
PubMed: 36213268
DOI: 10.3389/fendo.2022.951133 -
BMC Cancer Sep 2022Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC. METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.
RESULTS
The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726).
CONCLUSIONS
Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Disease-Free Survival; Female; Humans; Mutation; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Receptor, ErbB-2
PubMed: 36131248
DOI: 10.1186/s12885-022-10078-5 -
Tumour Biology : the Journal of the... 2022Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies.
MATERIALS AND METHODS
PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study.
RESULTS
Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features.
CONCLUSION
APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.
Topics: Breast Neoplasms; Cytidine Deaminase; Disease-Free Survival; Female; Humans; Lung Neoplasms; Minor Histocompatibility Antigens; Proportional Hazards Models
PubMed: 36093650
DOI: 10.3233/TUB-211577 -
Archives of Academic Emergency Medicine 2022Knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. Therefore, this study aimed to... (Review)
Review
INTRODUCTION
Knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. Therefore, this study aimed to systematically review the adverse events reported for inactivated vaccines and Novavax.
METHODS
In this systematic review, the databases of PubMed, Scopus, Cochrane, and Web of Science were searched on September 15, 2021. Then we identified the eligible studies using a two-step title/abstract and full-text screening process. Data on the subjects, studies, and types of adverse events were extracted and entered in a word table, including serious, mild, local, and systemic adverse events as well as the timing of side effects' appearance.
RESULTS
Adverse effects of inactivated coronavirus vaccines side effects were reported from phases 1, 2, and 3 of the vaccine trials. The most common local side effects included injection site pain and swelling, redness, and pruritus. Meanwhile, fatigue, headache, muscle pain, fever, and gastrointestinal symptoms including abdominal pain and diarrhea were among the most common systemic adverse effects.
CONCLUSION
This systematic review indicates that inactivated COVID-19 vaccines, including Sinovac, Sinopharm, and Bharat Biotech, as well as the protein subunit vaccines (Novavax) can be considered as safe choices due to having milder side effects and fewer severe life-threatening adverse events.
PubMed: 36033990
DOI: 10.22037/aaem.v10i1.1585 -
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 -
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 -
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