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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 -
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 -
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 -
BMC Cardiovascular Disorders Oct 2020This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS).
METHODS
Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR).
RESULTS
Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = - 32.26; 95% CI: - 56.48 to - 8.76; P < 0.01; VASP-PRI: WMD = - 9.61; 95% CI: - 14.63 to - 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12-0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08-1.81; P = 0.01).
CONCLUSIONS
Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.
Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cell Adhesion Molecules; Female; Humans; Male; Microfilament Proteins; Middle Aged; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome
PubMed: 33004000
DOI: 10.1186/s12872-020-01603-0 -
PloS One 2020To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19.
METHODS AND FINDINGS
We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/μl and -123.6 (-170.6, -76.6) cells/μl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml).
CONCLUSIONS
Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.
Topics: Betacoronavirus; C-Reactive Protein; COVID-19; Coronavirus Infections; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Lymphocyte Count; Observational Studies as Topic; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Troponin I
PubMed: 33002041
DOI: 10.1371/journal.pone.0239802 -
The American Journal of Cardiology Nov 2020Since the emergence of the coronavirus disease 19 (COVID-19), a number of studies have reported the presence of cardiovascular diseases in affected patients and linked... (Comparative Study)
Comparative Study Meta-Analysis
Since the emergence of the coronavirus disease 19 (COVID-19), a number of studies have reported the presence of cardiovascular diseases in affected patients and linked them with a higher risk of mortality. We conducted an online search in Medline/PubMed to identify original cohorts comparing data between survivors and non-survivors from COVID-19. The presence of cardiovascular events and related biomarkers were compared between the 2 groups. Data on 1,845 hospitalized patients with COVID-19 were pooled from 12 comparative studies. The overall mortality rate in relation to COVID-19 was 17.6%. Men aged > 50 years old were more likely to die from COVID-19. Significant co-morbidities contributing to mortality were hypertension, diabetes mellitus, smoking, a previous history of cardiovascular disease including chronic heart failure, and cerebrovascular accidents. A significant relationship was observed between mortality and patient presentation with dyspnea, fatigue, tachycardia, and hypoxemia. Cardiovascular disease-related laboratory biomarkers related to mortality were elevated serum level of lactate dehydrogenase, creatine kinase, brain natriuretic peptide, and cardiac troponin I. Adverse cardiovascular disease-related clinical events preceding death were shock, arrhythmias, and acute myocardial injury. In conclusion, severe clinical presentation and elevated biomarkers in COVID-19 patients with established risk factors can predict mortality from cardiovascular causes.
Topics: Age Factors; Aged; Biomarkers; COVID-19; Cardiovascular Diseases; Cause of Death; China; Comorbidity; Coronavirus Infections; Female; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; Sex Factors; Survival Analysis; Survivors; Troponin I
PubMed: 32916148
DOI: 10.1016/j.amjcard.2020.08.044 -
European Journal of Medical Research Aug 2020More severe cases of COVID- 19 are more likely to be hospitalized and around one-fifth, needing ICU admission. Understanding the common laboratory features of COVID-19... (Meta-Analysis)
Meta-Analysis
BACKGROUND
More severe cases of COVID- 19 are more likely to be hospitalized and around one-fifth, needing ICU admission. Understanding the common laboratory features of COVID-19 in more severe cases versus non-severe patients could be quite useful for clinicians and might help to predict the model of disease progression. This systematic review and meta-analysis aimed to compare the laboratory test findings in severe vs. non-severe confirmed infected cases of COVID-19.
METHODS
Electronic databases were systematically searched in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar from the beginning of 2019 to 3rd of March 2020. Heterogeneity across included studies was determined using Cochrane's Q test and the I statistic. We used the fixed or random-effect models to pool the weighted mean differences (WMDs) or standardized mean differences and 95% confidence intervals (CIs).
FINDINGS
Out of a total of 3009 citations, 17 articles (22 studies, 21 from China and one study from Singapore) with 3396 ranging from 12 to1099 patients were included. Our meta-analyses showed a significant decrease in lymphocyte, monocyte, and eosinophil, hemoglobin, platelet, albumin, serum sodium, lymphocyte to C-reactive protein ratio (LCR), leukocyte to C-reactive protein ratio (LeCR), leukocyte to IL-6 ratio (LeIR), and an increase in the neutrophil, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine (Cr), erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), lactate dehydrogenase (LDH), fibrinogen, prothrombin time (PT), D-dimer, glucose level, and neutrophil to lymphocyte ratio (NLR) in the severe group compared with the non-severe group. No significant changes in white blood cells (WBC), Creatine Kinase (CK), troponin I, myoglobin, IL-6 and K between the two groups were observed.
INTERPRETATION
This meta-analysis provides evidence for the differentiation of severe cases of COVID-19 based on laboratory test results at the time of ICU admission. Future well-methodologically designed studies from other populations are strongly recommended.
Topics: Asia; Asian People; Betacoronavirus; Blood Coagulation; Blood Glucose; Blood Sedimentation; C-Reactive Protein; COVID-19; China; Clinical Laboratory Techniques; Coronavirus Infections; Disease Progression; Fibrin Fibrinogen Degradation Products; Hospitalization; Humans; Inflammation; Interleukin-6; L-Lactate Dehydrogenase; Lymphocytes; Neutrophils; Pandemics; Pneumonia, Viral; SARS-CoV-2; Singapore; Treatment Outcome; Troponin I
PubMed: 32746929
DOI: 10.1186/s40001-020-00432-3