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International Journal of Cardiology Sep 2022Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor β signalling pathway. Due to the recent... (Review)
Review
INTRODUCTION
Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor β signalling pathway. Due to the recent discovery of the underlying genetic mutations leading to LDS, the spectrum of characteristics and complications is not fully understood.
METHODS
Our search included five databases (Pubmed, SCOPUS, Web of Science, EMBASE and google scholar) and included variations of "Loeys-Dietz Syndrome" as search terms, using all available data until February 2021. All study types were included. Three reviewers screened 1394 abstracts, of which 418 underwent full-text review and 392 were included in the final analysis.
RESULTS
We identified 3896 reported cases of LDS with the most commonly reported features and complications being: aortic aneurysms and dissections, arterial tortuosity, high arched palate, abnormal uvula and hypertelorism. LDS Types 1 and 2 share many clinical features, LDS Type 2 appears to have a more aggressive aortic disease. LDS Type 3 demonstrated an increased prevalence of mitral valve prolapse and arthritis. LDS Type 4 and 5 demonstrated a lower prevalence of musculoskeletal and cardiovascular involvement. Amongst 222 women who underwent 522 pregnancies, 4% experienced an aortic dissection and the peripartum mortality rate was 1%.
CONCLUSION
We observed that LDS is a multisystem connective tissue disorder that is associated with a high burden of complications, requiring a multidisciplinary approach. Ongoing attempts to better characterise these features will allow clinicians to appropriately screen and manage these complications.
Topics: Aortic Dissection; Arteries; Connective Tissue Diseases; Female; Humans; Loeys-Dietz Syndrome; Mutation; Pregnancy
PubMed: 35662564
DOI: 10.1016/j.ijcard.2022.05.065 -
Oncotarget Nov 2016Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups.
RESULTS
A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8).
MATERIALS AND METHODS
PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data.
CONCLUSION
This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.
Topics: Asian People; Carcinoma, Non-Small-Cell Lung; China; ErbB Receptors; Europe; Female; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Mutation; Mutation Rate; Prevalence; Risk Factors; Smoking; White People
PubMed: 27738317
DOI: 10.18632/oncotarget.12587 -
Medicina (Kaunas, Lithuania) Aug 2021and are genes located in different chromosomes that are disproportionately associated with hereditary breast and ovarian cancer syndrome. Their association with other... (Review)
Review
and are genes located in different chromosomes that are disproportionately associated with hereditary breast and ovarian cancer syndrome. Their association with other cancers remains to be explored. We systematically reviewed cohort studies to explore the association of and with various cancers except lung cancer. We searched PubMed, Medline (EBSCOhost) and relevant articles published up to 10 May 2021. The odds ratio, standardised morbidity rate and cancer-specific standardised incidence ratio were pooled together as relative risk (RR) estimates. Twelve studies were included for analysis. mutation increased pancreatic and uterine cancers by around 3-5- and 1.5-fold, respectively. mutation did not increase brain cancer; colorectal cancer; prostate, bladder and kidney cancer; cervical cancer; or malignant melanoma. increased gastric cancer with RR = 2.15 (1.98-2.33). The meta-analysis results can provide clinicians and relevant families with information regarding increased specific cancer risk in and mutation carriers.
Topics: Breast Neoplasms; Cohort Studies; Female; Genes, BRCA1; Genes, BRCA2; Humans; Lung Neoplasms; Male; Mutation; Ovarian Neoplasms
PubMed: 34577828
DOI: 10.3390/medicina57090905 -
Molecular Diagnosis & Therapy Mar 2022Numerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed. (Review)
Review
INTRODUCTION
Numerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed.
OBJECTIVE
The aim of the current review was to systematically identify and analyze clinical trials that have evaluated MET inhibitors in various cancer types and to provide an overview of their clinical outcomes.
METHODS
An electronic literature search was carried out in the PubMed and Embase databases to identify published clinical trials related to MET inhibitors. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed for the systematic appraisal of the literature. Data related to clinical outcomes, including progression-free survival, overall survival, objective response rate, and overall tumor response, were extracted.
RESULTS
In total, 49 publications were included. Among these, 51.02% were phase II studies, 14.28% were randomized controlled trials, three were phase III studies, two were prospective observational studies, and the remainder were either phase I or Ib studies. The majority (44.89%) of articles reported the clinical outcomes of MET inhibitors, including small molecules, monoclonal antibodies, and other agents, in patients with non-small-cell lung cancer (NSCLC) harboring MET alterations. MET amplification, overexpression, and MET exon 14 skipping mutations were the major MET alteration types reported across the included studies. Clinical responses/outcomes varied considerably.
CONCLUSION
This systematic literature review provides an overview of the literature available in Embase and PubMed regarding MET-targeted therapies. MET-selective tyrosine kinase inhibitors (TKIs) (capmatinib, tepotinib, and savolitinib) may become a new standard of care in NSCLC, specifically with MET exon 14 skipping mutations. A combination of MET TKIs with epidermal growth factor receptor (EGFR) TKIs (osimertinib + savolitinib, tepotinib + gefitinib) may be a potential solution for MET-driven EGFR TKI resistance. Further, MET alteration (MET amplification/overexpression) may be an actionable target in gastric cancer and papillary renal cell carcinoma.
Topics: Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Mutation; Observational Studies as Topic; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met
PubMed: 35266116
DOI: 10.1007/s40291-021-00568-w -
International Journal of Molecular... Oct 2022Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy,... (Meta-Analysis)
Meta-Analysis Review
Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.
Topics: Humans; Rifampin; Dapsone; Leprostatic Agents; Ofloxacin; Drug Resistance, Bacterial; Mycobacterium leprae; Leprosy; Mutation; Amino Acids; Microbial Sensitivity Tests
PubMed: 36293307
DOI: 10.3390/ijms232012443 -
BMJ (Clinical Research Ed.) Oct 2019To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis.
OBJECTIVE
To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.
RESULTS
18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.
CONCLUSIONS
These results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42018111954.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Mutation; Network Meta-Analysis
PubMed: 31591158
DOI: 10.1136/bmj.l5460 -
Infectious Diseases of Poverty Nov 2021To date, coronavirus disease 2019 (COVID-19) becomes increasingly fierce due to the emergence of variants. Rapid herd immunity through vaccination is needed to block the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To date, coronavirus disease 2019 (COVID-19) becomes increasingly fierce due to the emergence of variants. Rapid herd immunity through vaccination is needed to block the mutation and prevent the emergence of variants that can completely escape the immune surveillance. We aimed to systematically evaluate the effectiveness and safety of COVID-19 vaccines in the real world and to establish a reliable evidence-based basis for the actual protective effect of the COVID-19 vaccines, especially in the ensuing waves of infections dominated by variants.
METHODS
We searched PubMed, Embase and Web of Science from inception to July 22, 2021. Observational studies that examined the effectiveness and safety of SARS-CoV-2 vaccines among people vaccinated were included. Random-effects or fixed-effects models were used to estimate the pooled vaccine effectiveness (VE) and incidence rate of adverse events after vaccination, and their 95% confidence intervals (CI).
RESULTS
A total of 58 studies (32 studies for vaccine effectiveness and 26 studies for vaccine safety) were included. A single dose of vaccines was 41% (95% CI: 28-54%) effective at preventing SARS-CoV-2 infections, 52% (31-73%) for symptomatic COVID-19, 66% (50-81%) for hospitalization, 45% (42-49%) for Intensive Care Unit (ICU) admissions, and 53% (15-91%) for COVID-19-related death; and two doses were 85% (81-89%) effective at preventing SARS-CoV-2 infections, 97% (97-98%) for symptomatic COVID-19, 93% (89-96%) for hospitalization, 96% (93-98%) for ICU admissions, and 95% (92-98%) effective for COVID-19-related death, respectively. The pooled VE was 85% (80-91%) for the prevention of Alpha variant of SARS-CoV-2 infections, 75% (71-79%) for the Beta variant, 54% (35-74%) for the Gamma variant, and 74% (62-85%) for the Delta variant. The overall pooled incidence rate was 1.5% (1.4-1.6%) for adverse events, 0.4 (0.2-0.5) per 10 000 for severe adverse events, and 0.1 (0.1-0.2) per 10 000 for death after vaccination.
CONCLUSIONS
SARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world. In the context of global pandemic and the continuous emergence of SARS-CoV-2 variants, accelerating vaccination and improving vaccination coverage is still the most important and urgent matter, and it is also the final means to end the pandemic.
Topics: COVID-19; COVID-19 Vaccines; Disease Outbreaks; Hospitalization; Humans; SARS-CoV-2
PubMed: 34776011
DOI: 10.1186/s40249-021-00915-3 -
Journal of Thrombosis and Haemostasis :... Jul 2016Essentials We performed a meta-analysis on thrombosis risk in thrombophilic oral contraceptive (COC)-users. The results support discouraging COC-use in women with a... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Essentials We performed a meta-analysis on thrombosis risk in thrombophilic oral contraceptive (COC)-users. The results support discouraging COC-use in women with a natural anticoagulant deficiency. Contrary, additive risk of factor V Leiden (FVL) or prothrombin-G20210A (PT) mutation is modest. Women with a FVL/PT-mutation as single risk factor can use COCs if alternatives are not tolerated.
SUMMARY
Background Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), which is shown to be more pronounced in women with hereditary thrombophilia. Currently, WHO recommendations state that COC-use in women with hereditary thrombophilias (antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden and prothrombin-G20210A mutation) is associated with an unacceptable health risk. Objective To perform a meta-analysis evaluating the additional risk of VTE in COC-users with thrombophilia. Methods The MEDLINE and EMBASE databases were searched on 10 February 2015 for potential eligible studies. A distinction was made between 'mild' (factor V Leiden and prothrombin-G20210A mutation) and 'severe' thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, double heterozygosity or homozygosity of factor V Leiden and prothrombin-G20210A mutation). Results We identified 12 case-control and three cohort studies. In COC-users, mild and severe thrombophilia increased the risk of VTE almost 6-fold (rate ratio [RR], 5.89; 95% confidence interval [CI], 4.21-8.23) and 7-fold (RR, 7.15; 95% CI, 2.93-17.45), respectively. The cohort studies showed that absolute VTE risk was far higher in COC-users with severe thrombophilia than in those with mild thrombophilia (4.3 to 4.6 vs. 0.49 to 2.0 per 100 pill-years, respectively), and these differences in absolute risks were also noted in non-affected women (0.48 to 0.7 vs. 0.19 to 0.0), but with the caveat that absolute risks were estimated in relatives of thrombophilic patients with VTE (i.e. with a positive family history). Conclusion These results support discouraging COC-use in women with severe hereditary thrombophilia. By contrast, additive VTE risk of mild thrombophilia is modest. When no other risk factors are present, (e.g. family history) COCs can be offered to these women when reliable alternative contraceptives are not tolerated.
Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Cohort Studies; Contraceptives, Oral, Combined; Factor V; Female; Heterozygote; Humans; Middle Aged; Mutation; Protein C Deficiency; Protein S Deficiency; Prothrombin; Risk Factors; Thrombophilia; Venous Thromboembolism; Young Adult
PubMed: 27121914
DOI: 10.1111/jth.13349 -
BioMed Research International 2022Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing... (Review)
Review
BACKGROUND
Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAF mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAF mutation potential of these lesions and new prevention strategies in PTC patients.
METHODS
A total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAF mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021.
RESULTS
The following variables were associated with an increased risk of BRAF mutation in PTC patients: age ≥ 45 years (OR = 1.39, 95%CI = 1.21-1.60, < 0.00001), male gender (OR = 1.13, 95%CI = 0.99-1.28, = 0.06), multifocality (OR = 1.22, 95%CI = 1.07-1.40, = 0.004), lymph node metastasis (OR = 1.33, 95%CI = 0.79-2.23, = 0.28), extrathyroidal extension + (OR = 1.61, 95%CI = 1.06-2.44, = 0.03), vascular invasion + (OR = 2.04, 95%CI = 1.32-3.15, = 0.001), and tumor node metastasis stage (OR = 1.61, 95%CI = 1.38-1.88, < 0.00001). In addition, tumor size (>1 cm) (OR = 0.51, 95%CI = 0.32-0.81, = 0.005) and distant metastasis (OR = 0.69, 95%CI = 0.22-2.21, = 0.54) had no association or risk with BRAF mutation in PTC patients.
CONCLUSION
Our systematic review identified the following significant risk factors of BRAF mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAF mutation in PTC patients.
Topics: Carcinoma, Papillary; Humans; Lymphatic Metastasis; Male; Middle Aged; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 35647194
DOI: 10.1155/2022/9959649 -
International Journal of Cancer Jun 2017Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung... (Comparative Study)
Comparative Study Meta-Analysis Review
Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta-analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.
Topics: Afatinib; Carcinoma, Non-Small-Cell Lung; Diarrhea; Disease-Free Survival; ErbB Receptors; Erlotinib Hydrochloride; Exanthema; Gefitinib; Humans; Lung Neoplasms; Mutation; Outcome Assessment, Health Care; Proportional Hazards Models; Protein Kinase Inhibitors; Quinazolines; Randomized Controlled Trials as Topic
PubMed: 28295308
DOI: 10.1002/ijc.30691