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Scientific Reports Feb 2021Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with evidence suggesting they represent a heterogeneous population. This study... (Meta-Analysis)
Meta-Analysis
Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with evidence suggesting they represent a heterogeneous population. This study summarises the prognostic role of all proteins characterised in CAFs with immunohistochemistry in non-small cell lung cancer thus far. The functions of these proteins in cellular processes crucial to CAFs are also analysed. Five databases were searched to extract survival outcomes from published studies and statistical techniques, including a novel method, used to capture missing values from the literature. A total of 26 proteins were identified, 21 of which were combined into 7 common cellular processes key to CAFs. Quality assessments for sensitivity analyses were carried out for each study using the REMARK criteria whilst publication bias was assessed using funnel plots. Random effects models consistently identified the expression of podoplanin (Overall Survival (OS)/Disease-specific Survival (DSS), univariate analysis HR 2.25, 95% CIs 1.80-2.82) and α-SMA (OS/DSS, univariate analysis HR 2.11, 95% CIs 1.18-3.77) in CAFs as highly prognostic regardless of outcome measure or analysis method. Moreover, proteins involved in maintaining and generating the CAF phenotype (α-SMA, TGF-β and p-Smad2) proved highly significant after sensitivity analysis (HR 2.74, 95% CIs 1.74-4.33) supporting attempts at targeting this pathway for therapeutic benefit.
Topics: Actins; Biomarkers, Tumor; Cancer-Associated Fibroblasts; Carcinoma, Non-Small-Cell Lung; Fibroblasts; Genetic Heterogeneity; Humans; Lung Neoplasms; Phenotype; Prognosis; Smad2 Protein; Transforming Growth Factor beta; Tumor Microenvironment
PubMed: 33580106
DOI: 10.1038/s41598-021-81796-2 -
Clinical Chemistry and Laboratory... Jun 2021Cardiac troponins (cTn) are the preferred biomarkers for the evaluation of myocardial injury and play a key role in the diagnosis of acute myocardial infarction (MI)....
Cardiac troponins (cTn) are the preferred biomarkers for the evaluation of myocardial injury and play a key role in the diagnosis of acute myocardial infarction (MI). Pre-analytical or analytical issues and interferences affecting troponin T and I assays are therefore of major concern given the risk of misdiagnosis. False positive troponin results have been related to various interferences including anti-troponin antibodies, heterophilic antibodies, or elevated alkaline phosphatase level. On the other hand, false negative results have been reported in the case of a large biotin intake. These interferences are characterized with erroneous but reproducible troponin results. Of interest, non-reproducible results have also been reported in the literature. In other words, if the sample is reanalyzed a second time, a significant difference in troponin results will be observed. These interferences have been named "fliers" or "outliers". Compared to the biotin interference that received major attention in the literature, troponin outliers are also able to induce harmful clinical consequences for the patient. Moreover, the prevalence of outliers in recent studies was found to be higher (0.28-0.57%) compared to the biotin interference. The aim of this systematic review is to warn clinicians about these non-reproducible results that may alter their clinical judgment. Four case reports that occurred in the Clinique of Saint-Luc Bouge are presented to attest this point. Moreover, we aimed at identifying the nature of these non-reproducible troponin results, determining their occurrence, and describing the best way for their identification.
Topics: Biomarkers; Biotin; Humans; Myocardial Infarction; Troponin I; Troponin T
PubMed: 33554552
DOI: 10.1515/cclm-2020-1564 -
Angiology Jul 2021We systematically searched the literature to assess the efficacy of trimetazidine in reducing periprocedural myocardial injury and improving postoperative left... (Meta-Analysis)
Meta-Analysis
We systematically searched the literature to assess the efficacy of trimetazidine in reducing periprocedural myocardial injury and improving postoperative left ventricular ejection fraction (LVEF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). An electronic search was conducted based on the PubMed, Ovid, Scopus, Springer, CENTRAL, and Google Scholar databases; 14 randomized controlled trials (RCTs) were included. Our meta-analysis showed a significant reduction in cardiac troponin I (cTnI) levels with trimetazidine compared with controls ( < .00001) but not in serum creatine kinase-myocardial band levels ( = .49). There were significantly reduced odds of ischemic ST-T segment changes with trimetazidine ( = .0.03) but lack of significant difference in the incidence of anginal attacks between the 2 groups ( = .10). Results also suggest significantly higher LVEF with trimetazidine compared with controls ( < .00001). Meta-regression analysis indicated no influence of duration of trimetazidine therapy on cTnI levels. The administration of preprocedure trimetazidine may have a role in reducing periprocedural myocardial injury in patients with CAD undergoing PCI. Evidence also suggests that postoperative trimetazidine may improve LVEF in the short term. Lack of high-quality trials and the heterogeneity of studies limit the ability of our analysis to draw strong conclusions. Further well-designed RCTs are required to supplement current evidence.
Topics: Biomarkers; Cardiovascular Agents; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Myocardial Reperfusion Injury; Myocardium; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Stroke Volume; Treatment Outcome; Trimetazidine; Troponin I; Ventricular Function, Left
PubMed: 33472383
DOI: 10.1177/0003319720987745 -
Seminars in Arthritis and Rheumatism Feb 2021Systemic sclerosis (SSc) heart involvement (SHI) is a leading cause of SSc-associated mortality and once clinically overt, carries a very poor prognosis. There remain no... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) heart involvement (SHI) is a leading cause of SSc-associated mortality and once clinically overt, carries a very poor prognosis. There remain no established diagnostic criteria for SHI. This study aimed to systematically review the literature regarding the role of cardiac troponin (cTn) and B-type natriuretic peptide (BNP) or N-terminal B-type natriuretic peptide (NT-proBNP) in the diagnosis of SHI.
METHODS
A comprehensive search of the MEDLINE (Ovid), EMBASE and Pubmed databases was performed to identify adult human studies of at least 10 SSc patients with a primary focus of SHI that included data on cTn and BNP or NT-proBNP results. Only cohort studies and case-controlled studies were identified and the quality of the evidence presented in each study was assessed according to the Newcastle-Ottawa Quality Assessment Scale.
RESULTS
Of the 2742 studies identified by the database search, 12 articles fulfilled the study inclusion criteria. Three out of four studies evaluating SHI using cardiac magnetic resonance imaging found no association between cardiac biomarkers and imaging changes. By comparison echocardiographic abnormalities, cardiac arrhythmias and congestive cardiac failure were more likely to be associated with elevated cardiac biomarkers. Comparison of results between studies was limited by the highly heterogenous definitions of SHI and inclusion criteria employed across studies.
CONCLUSION
There are insufficient data to draw definitive conclusions about the role of cTn and BNP / NT-proBNP in the diagnosis of SHI. Currently available literature suggests that cardiac biomarkers may have some role, in conjunction with other diagnostic modalities, in identifying SHI; however, this remains a much-needed area of clinical research.
Topics: Adult; Biomarkers; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Scleroderma, Systemic; Troponin
PubMed: 33434765
DOI: 10.1016/j.semarthrit.2020.10.016 -
Clinical Chemistry Jan 2021We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial...
BACKGROUND
We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain.
METHODS
Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used.
RESULTS
Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge.
CONCLUSION
Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI.
PROSPERO REGISTRATION
CRD42019154716.
Topics: Adult; Algorithms; Angina Pectoris; Diagnostic Tests, Routine; Humans; Non-ST Elevated Myocardial Infarction; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Troponin I; Troponin T
PubMed: 33418577
DOI: 10.1093/clinchem/hvaa280 -
International Heart Journal Jan 2021The aim of this study was to evaluate the clinical efficacy of N-acetylcysteine (NAC) in the treatment of ST segment elevation myocardial infarction (STEMI).PubMed,... (Meta-Analysis)
Meta-Analysis
The aim of this study was to evaluate the clinical efficacy of N-acetylcysteine (NAC) in the treatment of ST segment elevation myocardial infarction (STEMI).PubMed, EMBASE, Cochrane Library, and Web of Science were searched systematically from the establishment of the database to June 2020. Two researchers independently completed literature screening and data extraction and conducted a meta-analysis.Nine articles including 1419 patients were enrolled. Meta-analysis showed that all-cause mortality [RR = 0.56, 95%CI (0.33, 0.93), P = 0.02], occurrence of major adverse cardiovascular events (MACE) [RR = 0.63, 95%CI (0.47, 0.85), P = 0.002], and myocardial enzyme hs-TnT level [SMD = -0.42, 95%CI (-0.71, -0.13), P = 0.005] were significantly lower in patients with STEMI treated with NAC than those in the control group. There was no significant difference between the NAC group and the control group in new congestive heart failure [RR = 0.94, 95%CI (0.48, 1.82), P = 0.84], ejection fraction [MD = 2.00, 95%CI (-0.59, 4.60), P = 0.13], and CK-MB [SMD = -0.18, 95%CI (-0.47, 0.11), P = 0.23]. There was no significant difference in the occurrence of adverse reactions between the NAC group and the control group [RR = 1.04, 95%CI (0.57-1.89), P = 0.90].NAC can reduce the all-cause mortality and MACE cases of STEMI.
Topics: Acetylcysteine; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Case-Control Studies; Creatine Kinase, MB Form; Female; Free Radical Scavengers; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Stroke Volume; Treatment Outcome; Troponin T
PubMed: 33390565
DOI: 10.1536/ihj.20-519 -
Clinical Chemistry Jan 2021Many studies have assessed the biological variation (BV) of cardiac-specific troponins (cTn), reporting widely varying within-subject BV (CVI) estimates. The aim of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many studies have assessed the biological variation (BV) of cardiac-specific troponins (cTn), reporting widely varying within-subject BV (CVI) estimates. The aim of this study was to provide meta-analysis-derived BV estimates for troponin I (cTnI) and troponin T (cTnT) for different sampling intervals and states of health.
METHODS
Relevant studies were identified by a systematic literature search. Studies were classified according to their methodological quality by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Meta-analyses of BIVAC-compliant studies were performed after stratification by cTn isoform, exclusion of results below the limit of detection, states of health, and sampling interval to deliver reference change values (RCV), index of individuality (II) and analytical performance specifications (APS) for these settings.
RESULTS
Sixteen and 15 studies were identified for cTnI and cTnT, respectively, out of which 6 received a BIVAC grade A. Five studies had applied contemporary cTnI assays, but none contemporary cTnT. High-sensitivity (hs-) cTnI and cTnT delivered similar estimates in all settings. Long-term CVI estimates (15.1; 11.3%) derived from healthy individuals were higher than short-term (4.3%; 5.3%) for hs-cTnI and hs-cTnT, respectively, although confidence intervals overlapped. Estimates derived from diseased subjects were similar to estimates in healthy individuals for all settings.
CONCLUSIONS
This study provides robust estimates for hs-cTnI and hs-cTnT applicable for different clinical settings and states of health, allowing for the use of RCV both to aid in the diagnosis of myocardial injury and for prognosis. BV-based APS appear too strict for some currently available technologies.
Topics: Biological Variation, Individual; Biomarkers; Cardiovascular Diseases; Humans; Kidney Diseases; Prognosis; Reference Values; Troponin I; Troponin T
PubMed: 33279972
DOI: 10.1093/clinchem/hvaa261 -
Archives of Iranian Medicine Nov 2020Coronavirus disease 2019 (COVID-19) has been widespread since late December 2019, with several symptoms related to the upper and lower respiratory system. However, its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronavirus disease 2019 (COVID-19) has been widespread since late December 2019, with several symptoms related to the upper and lower respiratory system. However, its cardiac manifestations are less frequently studied. We aimed to analyze the available COVID-19 data on acute cardiac injury, using troponin and brain natriuretic peptide (BNP) levels.
METHODS
We performed a systematic review on Medline/PubMed, Scopus, and Google Scholar databases until March 25, 2020. Relevant records reporting the incidence of acute cardiac injury as well as troponin and BNP levels were collected from published peer-reviewed articles with further analysis according to the clinical status of the patients (severe, non-severe, and death).
RESULTS
Eleven records of 1394 individuals were included. The mean age of patients with acute cardiac injury was 56.6 ± 33.4 years (males: 54.3%). The incidence of acute cardiac injury was 15% (95% CI: 11, 20%). Further analysis revealed that dead or severe patients had significantly higher percentages of myocardial injury, compared to non-severe ones (peer-reviewed: 44%, 95% CI: 16, 74% vs. 24%, 95% CI: 15, 34% vs. 5%, 95% CI: 1, 12%, respectively). Mean total troponin was 10.23 pg/mL (95% CI: 5.98, 14.47), while 13% (95% CI: 8%, 18%) of patients had elevated levels. Mean BNP was 216.74 pg/mL (95% CI: 3.27, 430.20).
CONCLUSION
Acute cardiac injury in COVID-19 patients is more frequent than what was expected at the beginning of the outbreak. Meanwhile, further studies are needed to investigate the utility of cardiac biomarkers as diagnostic and prognostic tools for long-term cardiac complications of this infection.
Topics: Adult; Aged; Biomarkers; COVID-19; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pandemics; SARS-CoV-2; Troponin
PubMed: 33220700
DOI: 10.34172/aim.2020.107 -
Trends in Endocrinology and Metabolism:... Dec 2020Coronavirus disease 2019 (COVID-19) patients with pre-existing cardiovascular disease (CVD) or with cardiovascular complications have a higher risk of mortality. The...
Coronavirus disease 2019 (COVID-19) patients with pre-existing cardiovascular disease (CVD) or with cardiovascular complications have a higher risk of mortality. The main cardiovascular complications of COVID-19 include acute cardiac injury, acute myocardial infarction (AMI), myocarditis, arrhythmia, heart failure, shock, and venous thromboembolism (VTE)/pulmonary embolism (PE). COVID-19 can cause cardiovascular complications or deterioration of coexisting CVD through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply-demand mismatch. We systematically review cardiovascular manifestations, histopathology, and mechanisms of COVID-19, to help to formulate future research goals and facilitate the development of therapeutic management strategies.
Topics: Angiotensin-Converting Enzyme 2; Arrhythmias, Cardiac; COVID-19; Cardiovascular Diseases; Cytokine Release Syndrome; Heart Diseases; Heart Failure; Humans; Hypoxia; Myocardial Infarction; Myocarditis; Pulmonary Embolism; Renin-Angiotensin System; SARS-CoV-2; Shock; Troponin; Venous Thromboembolism
PubMed: 33172748
DOI: 10.1016/j.tem.2020.10.001 -
Biomedical Journal Apr 2021The association between acute infections and cardiac injury, including myocarditis and acute myocardial infarction, is now well established. We have performed a...
The association between acute infections and cardiac injury, including myocarditis and acute myocardial infarction, is now well established. We have performed a systematic literature review for analyzing the results of epidemiological studies that measured cardiac troponins (cTn) in patients with Influenza virus infections. Overall, 14 articles were finally identified and analyzed. Taken together, the results of the scientific literature suggest that cTn elevation is a relatively rare phenomenon in patients with Influenza virus infection, with frequency generally comprised between 0 and 33%, more likely in elderly patients with significant comorbidities. In patients with modest cTn elevations, this phenomenon is apparently self-limited, transient and reversible, and especially involves patients with Influenza A (especially H1N1). In the minority of patients exhibiting an abrupt appearance of cardiovascular symptoms and concomitant elevation of cTn values, the relative increase of this biomarker reflects the presence of an underlying cardiac injury, that can be either myocarditis or an acute ischemic episode. Enhanced cTn values can also be more frequently observed in Influenza patients with complicated disease, in those developing acute respiratory distress syndrome and cardiac dysfunction, as well as in those at higher risk of death. cTn measurement shall be considered a valuable option in all patients developing acute cardiovascular symptoms during Influenza virus infections, as well as in those bearing cardiac or extra-cardiac comorbidities who bear a higher risk of complications.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza, Human; Male; Middle Aged; Myocardial Infarction; Troponin; Young Adult
PubMed: 33097442
DOI: 10.1016/j.bj.2020.06.001