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Indian Heart Journal 2022To assess the safety and efficacy of omecamtiv mecarbil compared with placebo in heart failure (HF) patients. (Meta-Analysis)
Meta-Analysis Review
AIM
To assess the safety and efficacy of omecamtiv mecarbil compared with placebo in heart failure (HF) patients.
METHODS
We searched PubMed, Web of Science, Cochrane Library, and SCOPUS until August 15th, 2021. We included all randomized controlled studies comparing omecamtiv mecarbil with placebo in heart failure patients. The meta-analysis was carried out using Rev Man software V5.4.
RESULTS
A total of eight studies were included in our systematic review. Pooled analysis showed that omecamtiv mecarbil is not associated with increased incidence of death, any adverse events, hypotension, heart failure, ventricular tachyarrhythmia, dyspnea, dizziness, and serious adverse events. Regarding the efficacy, omecamtiv mecarbil significantly reduced heart rate with some studies demonstrating its significant improvement in left ventricular ejection fraction and systolic function.
CONCLUSION
Omecamtiv mecarbil is a well-tolerated drug in heart failure patients. The limited data regarding the efficacy suggested that it may improve ejection fraction and systolic function.
Topics: Cardiac Myosins; Heart Failure; Humans; Stroke Volume; Urea; Ventricular Function, Left
PubMed: 35301008
DOI: 10.1016/j.ihj.2022.03.005 -
The Netherlands Journal of Medicine Jan 2014A systematic review was carried out to study the pattern of high-sensitivity cardiac troponin release after running (search performed on PubMed, ISI Web of Knowledge and... (Review)
Review
A systematic review was carried out to study the pattern of high-sensitivity cardiac troponin release after running (search performed on PubMed, ISI Web of Knowledge and Scopus databases). A total of ten reports were identified as meeting the pre-specified criteria (eight using high-sensitivity troponin T and two using high-sensitivity troponin I). The papers were published between 2009 and 2013, amounting to a total of 479 participants under study. Eight reports provided data comparing post-running troponin levels with the 99th percentile reference value. A total number of 296 participants, out of 424, showed post-running high-sensitivity troponin values higher than the 99th percentile reference value (69.8%). In conclusion, using high-sensitivity cardiac troponin assays, studies have shown that elevated post-running values are seen in more than two-thirds of runners. Whether troponin release in this setting represents a fully reversible phenomenon is currently unknown; the effects of strenuous running on long-term health are also uncertain.
Topics: Adolescent; Adult; Biomarkers; Diagnostic Techniques, Cardiovascular; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Qualitative Research; Reference Values; Running; Sensitivity and Specificity; Troponin I; Troponin T; Young Adult
PubMed: 24457432
DOI: No ID Found -
Journal of the Royal Society of Medicine Oct 2012To investigate the cardioprotective efficacy of remote ischaemic preconditioning (RIPC) in cardiac surgery. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the cardioprotective efficacy of remote ischaemic preconditioning (RIPC) in cardiac surgery.
DESIGN
We have performed a systematic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify randomized controlled trials involving RIPC.
SETTING
Randomized controlled trials of RIPC in open cardiac surgery patients.
MAIN OUTCOME MEASURES
Meta-analysis was performed with the primary outcome the standardized mean difference between intervention and control groups in 12 hour postoperative troponin concentration. Heterogeneity was examined by fixed effects meta-regression.
RESULTS
Ten studies with a total of 693 participants were included in the meta-analysis. RIPC reduced troponin levels 12 hours after surgery compared with control. The fixed and random effects differences were 0.35 (95% CI 0.19 to 0.51) and 0.53 (95% CI 0.18-0.88) respectively. However, important heterogeneity was present. Fixed effects meta-regression partially accounted for heterogeneity based on whether studies had full blinding, comprising blinding of patients, surgeons, anaesthetists and investigators. Studies with incomplete or no blinding demonstrated a larger estimate of effect, 0.74 (95% CI 0.47 to 1.00) compared to those with full blinding, 0.13 (95% CI - 0.07 to 0.33).
CONCLUSIONS
Although our analysis suggests RIPC may result in cardiac protection during cardiac surgery, the effect was most marked in studies without full blinding, with a smaller and statistically non-significant effect in fully blinded studies. We propose that further double blind randomized controlled trials investigating the cardioprotective effects of RIPC in cardiac surgery are required to resolve the current clinical uncertainty.
Topics: Cardiac Surgical Procedures; Coronary Artery Bypass; Double-Blind Method; Humans; Ischemic Preconditioning; Myocardial Reperfusion Injury; Postoperative Complications; Thoracic Surgery; Troponin
PubMed: 23104947
DOI: 10.1258/jrsm.2012.120049 -
Journal of the Peripheral Nervous... Jun 2022Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were... (Review)
Review
BACKGROUND AND AIMS
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were described in populations with Caucasian ancestry, genetic research on CMT in Africa is scant. Only a few cases of CMT have been reported, mainly from North Africa. The current study aimed to summarise available data on CMT in Africa, with emphasis on the epidemiological, clinical, and genetic features.
METHODS
We searched PubMed, Scopus, Web of Sciences, and the African Journal Online for articles published from the database inception until April 2021 using specific keywords. A total of 398 articles were screened, and 28 fulfilled our selection criteria.
RESULTS
A total of 107 families totalling 185 patients were reported. Most studies were reported from North Africa (n = 22). The demyelinating form of CMT was the commonest subtype, and the phenotype varied greatly between families, and one family (1%) of CMT associated with hearing impairment was reported. The inheritance pattern was autosomal recessive in 91.2% (n = 97/107) of families. CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
INTERPRETATION
This study reveals that CMT is not rare in Africa, and describes the current clinical and genetic profile. The review emphasised the urgent need to invest in genetic research to inform counselling, prevention, and care for CMT in numerous settings on the continent.
Topics: Africa; Charcot-Marie-Tooth Disease; Genes, Recessive; Humans; Microfilament Proteins; Mutation; Phenotype; Proteins
PubMed: 35383421
DOI: 10.1111/jns.12489 -
BMC Medicine Feb 2013Fascin-1 is an actin-bundling protein expressed in many human carcinomas, although absent from most normal epithelia. Fascin-1 promotes filopodia formation, migration... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fascin-1 is an actin-bundling protein expressed in many human carcinomas, although absent from most normal epithelia. Fascin-1 promotes filopodia formation, migration and invasion in carcinoma cells; in mouse xenograft tumor models it contributes to metastasis. Fascin-1 is an interesting candidate biomarker for aggressive, metastatic carcinomas but data from individual studies of human tumors have not yet been pooled systematically.
METHODS
This systematic review was conducted in accordance with PRISMA guidelines, using fixed and random effects models, as appropriate, to undertake meta-analysis.
RESULTS
A total of 26 immunohistochemical studies of 5 prevalent human carcinomas were identified for meta-analysis. Fascin-1 was associated with increased risk of mortality for breast (pooled hazard ratio, (HR) = 2.58; 95% confidence interval (CI) 1.48 to 4.52; P = 0.001), colorectal (HR = 1.60 (1.37 to 1.86; P <0.001) and esophageal carcinomas (HR = 1.35; CI 1.13 to 1.60; P = 0.001). There was no evidence of association of fascin-1 with mortality in gastric and lung carcinomas. Fascin-1 was associated with increased risk of disease progression in breast (HR = 2.48; CI 1.38 to 4.46; P = 0.002) and colorectal carcinomas (HR = 2.12; CI 1.00 to 4.47; P = 0.05), but not with progression of lung carcinomas (HR = 0.95; CI 0.49 to 1.85; P = 0.9). Fascin-1 was associated with increased risk of lymph node metastasis in colorectal (pooled risk ratio (RR) = 1.47; CI 1.26 to 1.71; P <0.001) and gastric carcinomas (RR = 1.43; CI 1.21 to 1.70; P <0.001). There was no evidence of association of fascin-1 with lymph node metastasis in lung or esophageal carcinomas. Fascin-1 was associated with increased risk of distant metastasis in colorectal (RR = 1.70; CI 1.18 to 2.45; P = 0.004) and gastric carcinomas (RR = 1.93; CI 1.21 to 3.33; P = 0.02). No association with distant metastasis in esophageal carcinomas was observed. Pooling across all the carcinomas provided strong evidence for association of fascin-1 with increased risk of mortality (HR = 1.44; CI 1.24 to 1.68; P <0.001; n = 3,645), lymph node metastasis (RR = 1.36; CI 1.18 to 1.55; P <0.001; n = 2,906) and distant metastasis (1.76; 1.34 to 2.32; P <0.001; n = 1,514).
CONCLUSIONS
Fascin-1 is associated consistently with increased risk of mortality in breast, colorectal and esophageal carcinomas and with metastasis in colorectal and gastric carcinomas. The results were stable to various sensitivity analyses and did not vary by predefined subgroups. These data will assist rational decision making for focusing investigations of fascin-1 as a biomarker or therapeutic target onto the most relevant carcinomas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma; Carrier Proteins; Disease Progression; Female; Humans; Immunohistochemistry; Male; Microfilament Proteins; Middle Aged; Neoplasm Metastasis; Young Adult
PubMed: 23442983
DOI: 10.1186/1741-7015-11-52 -
JAMA Nov 2017High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain.
OBJECTIVE
To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome.
DATA SOURCES
Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017.
STUDY SELECTION
Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction.
DATA EXTRACTION AND SYNTHESIS
The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data.
RESULTS
Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death.
CONCLUSIONS AND RELEVANCE
Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.
Topics: Acute Coronary Syndrome; Adult; Biomarkers; Death; Humans; Male; Myocardial Infarction; Prognosis; Prospective Studies; Risk Assessment; Troponin I
PubMed: 29127948
DOI: 10.1001/jama.2017.17488 -
British Journal of Anaesthesia Nov 2016Patients undergoing non-cardiac, non-vascular surgery are at risk of major cardiovascular complications. In non-cardiac surgery, troponin elevation has previously been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients undergoing non-cardiac, non-vascular surgery are at risk of major cardiovascular complications. In non-cardiac surgery, troponin elevation has previously been shown to be an independent predictor of major adverse cardiac events and postoperative mortality; however, a majority of studies have focused on vascular surgery patients. The aim of this meta-analysis was to determine whether troponin elevation is a predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery.
METHODS
A systematic review and meta-analysis was conducted in January 2016 according to the Meta-analysis Of Observational Studies in Epidemiology guidelines. Both interventional and observational studies measuring troponin within the first 4 days after surgery were eligible. A systematic search was performed in PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials.
RESULTS
Eleven eligible clinical studies (n=2193) were identified. A postoperative troponin elevation was a predictor of 30 day mortality, odds ratio (OR) 3.52 [95% confidence interval (CI) 2.21-5.62; I=0%], and an independent predictor of 1 yr mortality, adjusted OR 2.53 (95% CI 1.20-5.36; I=26%). A postoperative troponin elevation was associated with major adverse cardiac events at 30 days, OR 5.92 (95% CI 1.67-20.96; I=86%), and 1 yr after surgery, adjusted OR 3.00 (95% CI 1.43-6.29; I=21%).
CONCLUSIONS
Postoperative myocardial injury is an independent predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery. The meta-analysis provides evidence that supports troponin monitoring as a cardiovascular risk stratification tool.
Topics: Cardiovascular Diseases; Humans; Postoperative Complications; Troponin I
PubMed: 27799170
DOI: 10.1093/bja/aew321 -
Journal of Pediatric Gastroenterology... May 2022The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms...
BACKGROUND AND AIMS
The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms of intestinal dysmotility disorders. we aimed to describe the diverse phenotype of this newly reported and rare disease.
METHODS
Report of 4 new patients, and a systematic review of ACTG2-related disorders. we analyzed the population frequency and used in silico gene damaging predictions. Genotype-phenotype correlations were explored.
RESULTS
One hundred three patients (52% girls), from 14 publications, were included. Twenty-eight unique variants were analyzed, all exceedingly rare, and 27 predicted to be highly damaging. The median Combined Annotation Dependent Depletion (CADD) score was 29.2 (Interquartile range 26.3-29.4). Most patients underwent abdominal surgery (66%), about half required intermittent bladder catheterization (48.5%), and more than half were parenteral nutrition (PN)-dependent (53%). One-quarter of the patients died (25.7%), and 6 required transplant (5.8%). Girls had a higher rate of microcolon (P = 0.009), PN dependency (P = 0.003), and death/transplant (P = 0.029) compared with boys, and early disease onset (<2 years of age) was associated with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) features. There was no statistical association between disease characteristics and CADD scores.
CONCLUSIONS
Damaging ACTG2 variants are rare, often associated with MMIHS phenotype, and overall have a wide phenotypic variation. Symptoms usually present in the perinatal period but can also appear at a later age. The course of the disease is marked by frequent need for surgical interventions, PN support, and mortality. Poor outcomes are more common among girls with ACTG2 variants.
Topics: Abnormalities, Multiple; Actins; Colon; Female; Humans; Intestinal Pseudo-Obstruction; Male; Phenotype; Pregnancy; Urinary Bladder
PubMed: 35149643
DOI: 10.1097/MPG.0000000000003400 -
Anesthesiology Apr 2011There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery.
METHODS
The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate.
RESULTS
Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2-5.2), but there was substantial heterogeneity (I(2) = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1-10.9, I(2) = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4-2.3, I(2) = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5-4.0, I(2) = 4%).
CONCLUSIONS
An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.
Topics: Biomarkers; Cardiovascular Diseases; Creatine Kinase, MB Form; Humans; Prognosis; Surgical Procedures, Operative; Troponin
PubMed: 21336095
DOI: 10.1097/ALN.0b013e31820ad503 -
International Journal of Molecular... Dec 2022Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the... (Review)
Review
Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the non-genomic effects of CS seem to be mediated by putative non-classic membrane receptors characterized by pharmacological properties that are different from those of classic cytosolic GR. Since pre-clinical findings suggest that inhaled CS (ICS) may also regulate the bronchial contractile tone via putative CS membrane-associate receptors, the aim of this review was to systematically report and discuss the impact of CS on human airway smooth muscle (ASM) contractility and airway hyperresponsiveness (AHR). Current evidence indicates that CS have significant genomic/non-genomic beneficial effects on human ASM contractility and AHR, regardless of their anti-inflammatory effects. CS are effective in reducing either the expression, synthesis or activity of α-actin, CD38, inositol phosphate, myosin light chain kinase, and ras homolog family member A in response to several pro-contractile stimuli; overall these effects are mediated by the genomic action of CS. Moreover, CS elicited a strong bronchorelaxant effect via the rapid activation of the Gsα-cyclic-adenosine-monophosphate-protein-kinase-A pathway in hyperresponsive airways. The possibility of modulating the dose of the ICS in a triple ICS/long-acting β-adrenoceptor agonist/long-acting muscarinic antagonist fixed-dose combination supports the use of a Triple MAintenance and Reliever Therapy (TriMART) in those asthmatic patients at Step 3-5 who may benefit from a sustained bronchodilation and have been suffering from an increased parasympathetic tone.
Topics: Humans; Muscle, Smooth; Asthma; Bronchi; Muscle Contraction; Adrenal Cortex Hormones
PubMed: 36499612
DOI: 10.3390/ijms232315285