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Journal of Infection and Public Health Sep 2021To systematically investigate the relationship between cardiac biomarkers and COVID-19 severity and mortality. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically investigate the relationship between cardiac biomarkers and COVID-19 severity and mortality.
METHODS
We performed a literature search using PubMed, Web of Science, and Google Scholar. The standardized mean difference (SMD) and 95% confidence interval (CI) were applied to estimate the combined results of 67 studies. A meta-analysis of cardiac biomarkers was used to evaluate disease mortality and severity in COVID-19 patients.
RESULTS
A meta-analysis of 7812 patients revealed that patients with high levels of cardiac troponin I (SMD = 0.81 U/L, 95% CI = 0.14-1.48, P = 0.017), cardiac troponin T (SMD = 0.78 U/L, 95% CI = 0.07-1.49, P = 0.032), high-sensitive cardiac troponin I (SMD = 0.66 pg/mL, 95% CI = 0.51-0.81, P < 0.001), high-sensitive cardiac troponin T (SMD = 0.93 U/L, 95% CI = 0.21-1.65, P = 0.012), creatine kinase-MB (SMD = 0.54 U/L, 95% CI = 0.39-0.69, P < 0.001), and myoglobin (SMD = 0.80 U/L, 95% CI = 0.57-1.03, P < 0.001) were associated with prominent disease severity in COVID-19 infection. Moreover, 9532 patients with a higher serum level of cardiac troponin I (SMD = 0.51 U/L, 95% CI = 0.37-0.64, P < 0.001), high-sensitive cardiac troponin (SMD = 0.51 ng/L, 95% CI = 0.29-0.73, P < 0.001), high-sensitive cardiac troponin I (SMD = 0.51 pg/mL, 95% CI = 0.38-0.63, P < 0.001), high-sensitive cardiac troponin T (SMD = 0.85 U/L, 95% CI = 0.63-1.07, P < 0.001), creatine kinase-MB (SMD = 0.48 U/L, 95% CI = 0.32-0.65, P < 0.001), and myoglobin (SMD = 0.55 U/L, 95% CI = 0.45-0.65, P < 0.001) exhibited a prominent level of mortality from COVID-19 infection.
CONCLUSION
Cardiac biomarkers (cardiac troponin I, cardiac troponin T, high-sensitive cardiac troponin, high-sensitive cardiac troponin I, high-sensitive cardiac troponin T, creatine kinase-MB, and myoglobin) should be more frequently applied in identifying high-risk COVID-19 patients so that timely treatment can be implemented to reduce severity and mortality in COVID-19 patients.
Topics: Biomarkers; COVID-19; Creatine Kinase, MB Form; Humans; Myoglobin; Severity of Illness Index; Troponin I; Troponin T
PubMed: 34416596
DOI: 10.1016/j.jiph.2021.07.016 -
Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
Scientific Reports Jun 2023Many studies report Liver kinase B1 (LKB1) plays a critical role in gastric cancer (GC). However, the relationship between LKB1 and the clinicopathological parameters of... (Meta-Analysis)
Meta-Analysis
Many studies report Liver kinase B1 (LKB1) plays a critical role in gastric cancer (GC). However, the relationship between LKB1 and the clinicopathological parameters of GC patients remains controversial. This meta-analysis aimed to investigate the above question and re-evaluate the prognostic significance of LKB1 in GC patients. We searched PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, and Wan Fang to identify relevant studies published before April 20, 2023. After careful screening, 11 studies involving 1767 patients were included. We found that LKB1 expression was significantly related to tumor size (OR 0.515; 95% CI 0.316-0.839; P < 0.01), differentiation (OR 0.643; 95% CI 0.521-0.794; P < 0.001), depth of invasion (OR 0.397; 95% CI 0.319-0.494; P < 0.001), lymph node metastasis (OR 0.487; 95% CI 0.397-0.598; P = 0.01), and TNM stage (OR 0.362; 95% CI 0.293-0.447; P = 0.006). However, LKB1 was unrelated to gender and age (P > 0.05). Moreover, low LKB1 expression was significant correlate with overall survival (OS) (HR = 1.59; 95% CI 1.29-1.96; P < 0.001). In conclusion, LKB1 expression is related to tumor size, differentiation, depth of invasion, lymph node metastasis, and TNM stage, and low LKB1 expression can predict a poor prognosis. LKB1 is a potentially valuable prognosis signature and therapeutic target in GC patients.
Topics: Humans; Biomarkers, Tumor; Lymphatic Metastasis; Prognosis; Protein Serine-Threonine Kinases; Stomach Neoplasms
PubMed: 37264076
DOI: 10.1038/s41598-023-36239-5 -
The Breast Journal 2023Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a... (Review)
Review
BACKGROUND
Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a well-tolerated therapy, AI-induced musculoskeletal symptoms are common and may be accused for treatment discontinuation. Recently, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors changed the therapeutic setting, and currently, ribociclib, palbociclib, and abemaciclib are all approved in combination with nonsteroidal AIs in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. This systematic review aims to identify the frequency of aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) in the adjuvant setting in patients under AI monotherapy compared to patients under combination therapy with AIs and CDK4/6 inhibitors and demonstrate the underlying mechanism of action.
METHODS
This study was performed in accordance with PRISMA guidelines. The literature search and data extraction from all randomized clinical trials (RCTs) were done by two independent investigators. Eligible articles were identified by a search of MEDLINE and ClinicalTrial.gov database concerning the period 2000/01/01-2021/05/01.
RESULTS
Arthralgia was reported in 13.2 to 68.7% of patients receiving AIs for early-stage breast cancer, while arthralgia induced by CDK4/6 inhibitors occurred in a much lower rate [20.5-41.2%]. Bone pain (5-28.7% vs. 2.2-17.2%), back pain (2-13.4% vs. 8-11.2%), and arthritis (3.6-33.6% vs. 0.32%) were reported less frequently in patients receiving the combination of CDK4/6 inhibitors with ET.
CONCLUSIONS
CDK4/6 inhibitors might have a protective effect against joint inflammation and arthralgia occurrence. Further studies are warranted to investigate arthralgia incidence in this population.
Topics: Humans; Female; Aromatase Inhibitors; Breast Neoplasms; Arthralgia; Cyclin-Dependent Kinase 4
PubMed: 37293258
DOI: 10.1155/2023/3614296 -
Archives of Gerontology and Geriatrics Nov 2023Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to assess the accuracy and bias of six commonly used equations, including the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI) and its combination with cystatin C (CKD-EPI), with the corresponding pair of the Berlin Initiative Study equations (BIS1 and BIS2) and the Full Age Spectrum equations (FAS and FAS).
METHODS
PubMed and the Cochrane Library were searched for studies comparing estimated GFR (eGFR) with measured GFR (mGFR). We analyzed the difference in P30 and bias among the six equations and investigated subgroups based on the area (Asian and non-Asian), mean age (60-74 years and ≥75 years), and levels of mean mGFR (<45 mL/min/1.73m and ≥45 mL/min/1.73m).
RESULTS
27 studies with 18,112 participants were included, all reporting P30 and bias. BIS1 and FAS exhibited significantly higher P30 than CKD-EPI. While no significant differences were observed between FAS and BIS1, or among the three combined equations in terms of either P30 or bias. Subgroup analyses revealed FAS and FAS achieved better results in most situations. However, in the subgroup of mGFR<45 mL/min/1.73m, CKD-EPI had relatively higher P30 and significantly smaller bias.
CONCLUSIONS
Overall, BIS and FAS provided relatively more accurate estimates of GFR than CKD-EPI in older adults. FAS and FAS may be better suited for various conditions, while CKD-EPI would be a better option for older individuals with impaired renal function.
Topics: Aged; Humans; Asian; Creatinine; ErbB Receptors; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Middle Aged; Reproducibility of Results; Models, Biological
PubMed: 37379796
DOI: 10.1016/j.archger.2023.105107 -
International Journal of Molecular... Jul 2023The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal... (Meta-Analysis)
Meta-Analysis
Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression ( < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; ErbB Receptors; Head and Neck Neoplasms; Biomarkers, Tumor
PubMed: 37569265
DOI: 10.3390/ijms241511888 -
British Journal of Clinical Pharmacology May 2022The present systematic review and meta-analysis evaluated the incidence of elevated creatine phosphokinase (CPK) levels between daptomycin alone and concomitant... (Meta-Analysis)
Meta-Analysis Review
AIMS
The present systematic review and meta-analysis evaluated the incidence of elevated creatine phosphokinase (CPK) levels between daptomycin alone and concomitant daptomycin and statin use.
METHODS
We searched the PubMed, Web of Sciences, Cochrane Library and ClinicalTrials.gov databases. We analysed the incidence of elevated CPK between daptomycin alone and concomitant daptomycin and statins among studies defining CPK elevation as levels ≥ the upper limit of normal (ULN) or ≥5× ULN. We also analysed the incidence of rhabdomyolysis between the groups. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) based on the included studies.
RESULTS
Comparing CPK elevation defined as CPK levels ≥ULN, a significantly higher incidence of CPK elevation was observed with concomitant daptomycin and statin use than with daptomycin alone (OR = 2.55, 95% CI 1.78-3.64, P < .00001, I = 0%). Likewise, when CPK elevation was defined as CPK levels ≥5× ULN, a significantly higher incidence of CPK elevation was detected with concomitant daptomycin and statin use than with daptomycin alone (OR = 1.89, 95% CI 1.06-3.35, P = .03, I = 48%). The incidence of rhabdomyolysis was significantly higher following concomitant daptomycin and statin use than with daptomycin alone (OR = 11.60, 95% CI 1.81-74.37, P = .01, I = 0%).
CONCLUSION
The combined use of daptomycin and statins were significant risk factors for the incidence of CPK elevation defined as levels ≥ULN or ≥5× ULN and rhabdomyolysis.
Topics: Anti-Bacterial Agents; Creatine Kinase; Daptomycin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Retrospective Studies; Rhabdomyolysis
PubMed: 34902879
DOI: 10.1111/bcp.15172 -
International Journal of Molecular... Aug 2023The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers... (Meta-Analysis)
Meta-Analysis Review
The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25-4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: -0.23, CI95% -0.37 to -0.09; and SMD:0.24, CI95% 0.01-0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.
Topics: Pregnancy; Female; Humans; Phosphoric Monoester Hydrolases; Angiopoietin-1; Angiopoietin-2; Pre-Eclampsia; Antibodies; Receptor, trkA
PubMed: 37629025
DOI: 10.3390/ijms241612842 -
Medicine Jan 2022To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.
METHODS
A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).
RESULTS
A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I2 = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I2 = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).
CONCLUSION
In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.
ETHICS AND DISSEMINATION
This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.
INPLASY REGISTRATION NUMBER
INPLASY 202150010.
Topics: ErbB Receptors; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis
PubMed: 35060503
DOI: 10.1097/MD.0000000000028507 -
Biomolecules Sep 2023Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor... (Review)
Review
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer over the last decade. These inhibitors are currently established as first- and second-line systemic treatment choices for both endocrine-sensitive and -resistant breast cancer populations alongside endocrine therapy (ET) or monotherapy. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. Although these drugs have been demonstrated to prolong overall survival (as well as progression-free survival (PFS) in breast cancer patients), changing the paradigm of all current knowledge, they also cause important adverse events (AEs). This review provides the latest summary and update on the safety profile of the three CDK4/6 inhibitors, as it appears from all major phase II and III randomized clinical trials regarding palbociclib, ribociclib, and abemaciclib, including the most relevant 15 clinical trials.
Topics: Humans; Female; Breast Neoplasms; Progression-Free Survival; Cyclin-Dependent Kinase 4; Clinical Trials, Phase II as Topic
PubMed: 37759823
DOI: 10.3390/biom13091422