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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 -
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 -
Infection and Drug Resistance 2023Coronavirus disease 2019 (COVID-19) pandemic scared the whole world at the end of 2019, which is a communicable respiratory disease caused by severe acute respiratory... (Review)
Review
BACKGROUND
Coronavirus disease 2019 (COVID-19) pandemic scared the whole world at the end of 2019, which is a communicable respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In South Africa and other African countries, the COVID-19 vaccines were subsequently approved for emergency use by the respective national regulatory authorities. There is a paucity of aggregated data that revealed the safety and efficacy of COVID-19 vaccines in Africa.
OBJECTIVE
The aim of this systematic review was to synthesize the literature on the safety and efficacy of the COVID-19 vaccine which was given in Africa.
METHODS
A systematic search was conducted on Science Direct, PubMed, EMBASE, Google Scholar, CINAHL, Cochrane Library, and direct Google searches. Only studies written in English and published articles from 2019 to October 30, 2022, which comprise nine randomized clinical trials (RCT), and four different studies including a single-arm implementation trials, prospective study, retrospective cohort study, and test-negative designs were included.
RESULTS
A total of 13 studies were included which contain 810,466 participants from Africa. Of these, 62.18% of the participants were female. The efficacy of COVID-19 vaccine in Africa ranges from 41.7% to 100%. Moreover, vaccine efficacy against COVID-19 variants ranges from -5.7% to 100%. In general, systemic and local adverse events following vaccination in most trials were reported with a similar pattern between the placebo and vaccine groups. Out of the total reported adverse events, most of them were mild to moderate, whereas a few were serious.
CONCLUSION
Almost all current COVID-19 vaccines appear to be safe for African study participants. Regarding efficacy, the protein subunit vaccine and mRNA vaccine exhibited high efficacy (100%) in this group of participants. However, Ad26. COV2.S and ChAdOx1 nCoV-19 COVID-19 vaccines are not effective against the delta variant and B.1.351 variant, respectively.
PubMed: 37222988
DOI: 10.2147/IDR.S401074 -
Neurological Sciences : Official... Apr 2023KCNT1 has been known to encode a subunit of the tetrameric sodium activated potassium channel (K1.1). Pathogenic variants of KCNT1, especially gain-of-function (GOF)... (Review)
Review
KCNT1 has been known to encode a subunit of the tetrameric sodium activated potassium channel (K1.1). Pathogenic variants of KCNT1, especially gain-of-function (GOF) variants, are associated with multiple epileptic disorders which are often refractory to conventional anti-seizure medications and summarized as KCNT1-related epilepsy. Although the detailed pathogenic mechanisms of KCNT1-related epilepsy remain unknown, increasing studies attempt to find effective medications for those patients by utilizing quinidine to inhibit hyperexcitable K1.1. However, it has been shown that controversial outcomes among studies and partial success in some individuals may be due to multiple factors, such as poor blood-brain barrier (BBB) penetration, mutation-dependent manner, phenotype-genotype associations, and rational therapeutic schedule. In recent years, with higher resolution of K1.1 structure in different activation states and advanced synthetic techniques, it improves the process performance of therapy targeting at K1.1 channel to achieve more effective outcomes. Here, we systematically reviewed the study history of quinidine on KCNT1-related epilepsy and its corresponding therapeutic effects. Then, we analyzed and summarized the possible causes behind the different outcomes of the application of quinidine. Finally, we outlooked the recent advances in precision medicine treatment for KCNT1-related epilepsy.
Topics: Humans; Quinidine; Anticonvulsants; Potassium Channels, Sodium-Activated; Epilepsy; Potassium Channels; Mutation; Nerve Tissue Proteins
PubMed: 36437393
DOI: 10.1007/s10072-022-06521-x -
Sports Medicine and Arthroscopy Review Sep 2016Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review... (Review)
Review
Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.
Topics: Biomarkers; Brain Concussion; Glial Fibrillary Acidic Protein; Humans; Magnetic Resonance Imaging; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Tomography, X-Ray Computed; Ubiquitin Thiolesterase; tau Proteins
PubMed: 27482776
DOI: 10.1097/JSA.0000000000000117 -
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 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
Expert Review of Gastroenterology &... 2015We performed a systematic review and meta-analysis to estimate the polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-analysis to estimate the polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility.
METHODS
PubMed and Web of Science databases were searched (to June 2015) on IL18RAP rs917997 and CCR3 rs6441961 polymorphisms.
RESULTS
The meta-analysis included 16 and 7 studies for rs917997 and rs6441961, respectively. The minor risk A allele at both rs917997 and rs6441961 carried risks (odds ratios) of 1.24 (95% CI 1.18-1.31) and 1.21 (95% CI 1.12-1.31), respectively. These alleles contributed to increase risks in all celiac disease patients by 5.04 and 6.35%. The estimated lambdas were 0.73 and 0.51, suggesting that an additive model would be the best choice for both gene effects.
CONCLUSIONS
This meta-analysis provides robust estimates that IL18RAP rs917997 and CCR3 rs6441961 are potential risk factors for celiac disease in European populations. Studies are needed to confirm these findings in different ethnicities.
Topics: Celiac Disease; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin-18 Receptor beta Subunit; Polymorphism, Single Nucleotide; Receptors, CCR3; Risk Factors; White People
PubMed: 26289103
DOI: 10.1586/17474124.2015.1075880 -
PloS One 2014S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and... (Meta-Analysis)
Meta-Analysis Review
S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR) of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI). 20 studies were included totaling for 994 cases and 785 controls. Schizophrenia patients showed 76% higher S100B blood levels than controls with mMR = 1.76 95% CI: 1.44-2.15. No difference could be found between drug-free patients with mMR = 1.84 95%CI: 1.24-2.74 and patients on antipsychotic medication with mMR = 1.75 95% CI: 1.41-2.16). Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered.
Topics: Humans; S100 Calcium Binding Protein beta Subunit; Schizophrenia
PubMed: 25202915
DOI: 10.1371/journal.pone.0106342 -
Sexual Medicine Reviews Oct 2020Erectile dysfunction (ED) is usually developed from psychological, neurological, hormonal, and vascular pathologies or a combination of these factors. However, the...
INTRODUCTION
Erectile dysfunction (ED) is usually developed from psychological, neurological, hormonal, and vascular pathologies or a combination of these factors. However, the possible genetic polymorphisms that might underlie this disorder were not thoroughly investigated.
OBJECTIVES
This review article aimed to assess the possible involvement of gene polymorphisms in men with ED.
METHODS
A systematic review was conducted until January 2020 based on a search of all relevant articles in many electronic sites such as PubMed, Medline Medical Subject Headings, Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, and Egyptian Knowledge Bank databases with no language restriction. Keywords used to assess the outcome and estimates for relevant associations were sexual health, genes, erectile dysfunction, polymorphisms, and cavernous tissues.
RESULTS
Many genetic studies were carried out to inspect the contribution of different encoded genotypes and ED. Overall, 50 studies were reviewed and were classified as per the type of gene polymorphisms. These studies have investigated 10,174 men with ED compared with 6,891 healthy men as controls. 35 studies were case-controlled, 13 cross-sectional cohort studies, one retrospective study, and one genome-wide association study. So far, the most relevant gene polymorphisms linked with men with ED included endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), androgen receptor (AR) CAG repeat, G-protein β3 (GNB3) subunit, methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), TGFB1, proprotein convertase subtilisin/kexin type 9 (PCSK9), ARG1, DRD2, DRD4, DDAH, and HNF4A genes. Both PROGINS and IGFBP-3 polymorphisms were investigated in only one study each but with irrelevant significance.
CONCLUSIONS
Although several genetic studies exposed the association between different genotypes and men with ED with varied outcomes, such a relationship should not be overlooked. Therefore, more studies should be encouraged to elucidate the exact role, if any, for such association. Mostafa T, Taymour M. Gene Polymorphisms Affecting Erectile Dysfunction. Sex Med 2020;8:561-572.
Topics: Erectile Dysfunction; Genotype; Humans; Male; Polymorphism, Genetic
PubMed: 32169432
DOI: 10.1016/j.sxmr.2020.02.001