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PloS One 2017Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our... (Review)
Review
BACKGROUND
Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our aim was to create a systematic review of NETosis inducers and perform a standardized in vitro study of NETosis inducers important in (cardiac) wound healing.
METHODS
In vitro NETosis was studied by incubating neutrophils with PMA, living and dead bacteria (S. aureus and E. coli), LPS, (activated) platelets (supernatant), glucose and calcium ionophore Ionomycin using 3-hour periods of time-lapse confocal imaging.
RESULTS
PMA is a consistent and potent inducer of NETosis. Ionomycin also consistently resulted in extrusion of DNA, albeit with a process that differs from the NETosis process induced by PMA. In our standardized experiments, living bacteria were also potent inducers of NETosis, but dead bacteria, LPS, (activated) platelets (supernatant) and glucose did not induce NETosis.
CONCLUSION
Our systematic review confirms that there is much variation in study design and results of NETosis induction. Our experimental results confirm that under standardized conditions, PMA, living bacteria and Ionomycin all strongly induce NETosis, but real-time confocal imaging reveal different courses of events.
Topics: Escherichia coli; Extracellular Traps; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Myocardium; Staphylococcus aureus; Wound Healing
PubMed: 28486563
DOI: 10.1371/journal.pone.0176472 -
Cellular Physiology and Biochemistry :... 2018Patients with myocardial infarction and hypoxemia require supplemental oxygen. However, the current therapeutic paradigm is contradicted by several recent studies in... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Patients with myocardial infarction and hypoxemia require supplemental oxygen. However, the current therapeutic paradigm is contradicted by several recent studies in which the post-infarcted heart appears to benefit from systemic hypoxia. With this systematic review and meta-analysis, we aimed to discover whether systemic hypoxia is beneficial or detrimental to the infarcted myocardium.
METHODS
We conducted an electronic search of the PubMed, EMBASE, and Web of Science databases and extracted the outcomes of cardiac function, geometry, and hemodynamics. A random-effect model was applied when the I2 value of greater than 50%. The sensitivity analysis was performed by omitting one study at a time, and publication bias was assessed using Egger's test. In addition, the quality of studies was evaluated using the risk of bias tool devised by the Systematic Review Centre for Laboratory Animal Experimentation.
RESULTS
Six reports comprising 14 experiments were ultimately screened from among 10,323 initially identified preclinical studies. Few studies reported the method of randomization and none described allocation concealment, random outcome assessment or blinding. Overall, chronic hypoxia was found to have a beneficial effect on the ejection fraction (standard mean difference [SMD] = 5.39; 95% confidence interval [CI], 3.83 to 6.95; P < 0.001) of the infarcted heart, whereas acute hypoxia significantly improved hemodynamics, as indicated by an increase in the maximal rate of rise of left ventricular pressure (SMD = 1.27; 95% CI, 0.27 to 2.28; P = 0.013) and cardiac output (SMD = 1.26; 95% CI, 0.34 to 2.18; P = 0.007) and a decrease in total systematic vascular resistance (SMD = -0.89; 95% CI, -1.24 to -0.53; P < 0.001). Furthermore, a reduced oxygen content increased the stroke volume (P = 0.010). However, hypoxia reduced the end-systolic (SMD = -2.67; 95% CI, -4.09 to -1.26; P < 0.001) and end-diastolic (SMD = -3.61; 95% CI, -4.65 to -2.57; P < 0.001) left ventricular diameters and increased the total pulmonary resistance (SMD = 0.76; 95% CI, 0.20 to 1.33; P = 0.008), pulmonary arterial mean pressure (SMD = 2.02; 95% CI, 0.23 to 3.81; P = 0.027), and left atrial pressure (SMD = 1.20; 95% CI, 0.57 to 1.82; P < 0.001).
CONCLUSION
Hypoxia significantly improved heart function after infarction, with particular beneficial effects on systolic function and hemodynamics. However, it had slightly adverse effects on pulmonary circulation and left ventricular geometry. A lower inspired oxygen concentration may improve cardiac function, although further research is needed to determine the optimum level of hypoxia. Finally, more studies of hypoxia and myocardial infarction in larger species are required before these findings can be incorporated into therapeutic guidelines.
Topics: Animals; Blood Gas Analysis; Databases, Factual; Heart Ventricles; Hemodynamics; Hypoxia; Myocardial Infarction; Myocardium
PubMed: 30466079
DOI: 10.1159/000495397 -
Medicina (Kaunas, Lithuania) Jan 2023: The heart is the organ with the highest metabolic demand in the body, and it relies on high ATP turnover and efficient energy substrate utilisation in order to... (Review)
Review
: The heart is the organ with the highest metabolic demand in the body, and it relies on high ATP turnover and efficient energy substrate utilisation in order to function normally. The derangement of myocardial energetics may lead to abnormalities in cardiac metabolism, which herald the symptoms of heart failure (HF). In addition, phosphorus magnetic resonance spectroscopy (P MRS) is the only available non-invasive method that allows clinicians and researchers to evaluate the myocardial metabolic state in vivo. This review summarises the importance of myocardial energetics and provides a systematic review of all the available research studies utilising P MRS to evaluate patients with a range of cardiac pathologies. : We have performed a systematic review of all available studies that used P MRS for the investigation of myocardial energetics in cardiovascular disease. : A systematic search of the Medline database, the Cochrane library, and Web of Science yielded 1092 results, out of which 62 studies were included in the systematic review. The P MRS has been used in numerous studies and has demonstrated that impaired myocardial energetics is often the beginning of pathological processes in several cardiac pathologies. : The P MRS has become a valuable tool in the understanding of myocardial metabolic changes and their impact on the diagnosis, risk stratification, and prognosis of patients with cardiovascular diseases.
Topics: Humans; Phosphorus; Cardiovascular Diseases; Magnetic Resonance Spectroscopy; Myocardium; Heart Failure; Energy Metabolism
PubMed: 36676798
DOI: 10.3390/medicina59010174 -
Heart and Vessels Feb 2022Chronic myocarditis is a prolonged inflammatory condition in the myocardium and its histological manifestation is defined by the presence of an inflammatory infiltrate.... (Meta-Analysis)
Meta-Analysis
Chronic myocarditis is a prolonged inflammatory condition in the myocardium and its histological manifestation is defined by the presence of an inflammatory infiltrate. Chronic myocarditis has not been well known and its treatment of chronic myocarditis has not been established. Primary outcome of this study was to assess the efficacy of immunomodulatory treatment in addition to conventional treatment, and secondary outcomes were to clarity the prognosis of natural history of chronic myocarditis and incidence of chronic myocarditis in patients with dilated cardiomyopathy (DCM). We searched for studies in Medline, Embase, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi published between January 1946 and June 2020. Sixteen studies met the inclusion criteria. A meta-analysis revealed that patients receiving immunomodulatory treatment showed an improvement in left ventricular ejection fraction after immunomodulatory treatment compared to the control group (hazard ratio, 16.65; confidence interval, 4.55-28.74; p = 0.007). Five-year survival rate of the patients with inflammatory DCM (iDCM) and DCM was 52.7-70.3% and 51.9-91.1%, respectively. Moreover, 51.5%-62.7% of patients with DCM met the criteria of iDCM. Our systematic review revealed that patients with chronic myocarditis had poor prognosis and immunomodulatory treatment was significantly effective in addition to conventional treatment.
Topics: Biopsy; Cardiomyopathy, Dilated; Humans; Myocarditis; Myocardium; Stroke Volume; Ventricular Function, Left
PubMed: 34365565
DOI: 10.1007/s00380-021-01914-y -
Journal of Magnetic Resonance Imaging :... Apr 2018Although cardiac MR and T mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T values in healthy and diseased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although cardiac MR and T mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem contradictory.
PURPOSE
To determine the range of native myocardial T value ranges in patients with NICM and populations with increased cardiovascular risk.
STUDY TYPE
Systemic review and meta-analysis.
POPULATION
Patients with NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and patients with myocarditis (MC), iron overload, amyloidosis, Fabry disease, and populations with hypertension (HT), diabetes mellitus (DM), and obesity. FIELD STRENGTH/SEQUENCE: (Shortened) modified Look-Locker inversion-recovery MR sequence at 1.5 or 3T.
ASSESSMENT
PubMed and Embase were searched following the PRISMA guidelines.
STATISTICAL TESTS
The summary of standard mean difference (SMD) between the diseased and a healthy control populations was generated using a random-effects model in combination with meta-regression analysis.
RESULTS
The SMD for HCM, DCM, and MC patients were significantly increased (1.41, 1.48, and 1.96, respectively, P < 0.01) compared with healthy controls. The SMD for HT patients with and without left-ventricle hypertrophy (LVH) together was significantly increased (0.19, P = 0.04), while for HT patients without LVH the SMD was zero (0.03, P = 0.52). The number of studies on amyloidosis, iron overload, Fabry disease, and HT patients with LVH did not meet the requirement to perform a meta-analysis. However, most studies reported a significantly increased T for amyloidosis and HT patients with LVH and a significant decreased T for iron overload and Fabry disease patients.
DATA CONCLUSIONS
Native T mapping by using an (Sh)MOLLI sequence can potentially assess myocardial changes in HCM, DCM, MC, iron overload, amyloidosis, and Fabry disease compared to controls. In addition, it can help to diagnose left-ventricular remodeling in HT patients.
LEVEL OF EVIDENCE
2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:891-912.
Topics: Cardiomyopathies; Cardiovascular Diseases; Heart; Humans; Magnetic Resonance Imaging; Myocardium; Reference Values; Risk Factors
PubMed: 29131444
DOI: 10.1002/jmri.25885 -
Heart Failure Reviews Mar 2022Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that... (Review)
Review
Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that stabilizes TTR, has been used as an off-label therapeutic for ATTR-CM. Given limited data surrounding the use of diflunisal, a systematic review of the literature is warranted. We searched the PubMed, MEDLINE, and Embase databases for studies that reported on the use of diflunisal therapy for patients with ATTR-CM. We included English language studies which assessed the effect of diflunisal in adult patients with ATTR-CM who received diflunisal as primary treatment and reported clinical outcomes with emphasis on studies that noted the safety and efficacy of diflunisal in cardiac manifestations of ATTR amyloidosis. We excluded studies which did not use diflunisal therapy or used diflunisal therapy for non-cardiac manifestations of TTR amyloidosis. We also excluded case reports, abstracts, oral presentations, and studies with fewer than 10 subjects. Our search yielded 316 records, and we included 6 studies reporting on 400 patients. Non-comparative single-arm small non-randomized trials for diflunisal comprised 4 of the included studies. The 2 studies that compared diflunisal versus no treatment found improvements in TTR concentration, left atrial volume index, cardiac troponin I, and global longitudinal strain. Overall, diflunisal use was associated with decreased mortality and number of orthotopic heart transplant in ATTR-CM patients. Although a smaller number of patients had to stop treatment due to gastrointestinal side effects and transient renal dysfunction, there were no severe reactions reported in the studies included in our review. This systematic review supports the use of diflunisal for ATTR-CM. Additional long-term analyses and randomized clinical trials are needed to confirm these results.
Topics: Adult; Amyloid Neuropathies, Familial; Diflunisal; Humans; Myocardium; Prealbumin
PubMed: 34272629
DOI: 10.1007/s10741-021-10143-4 -
Biomarkers : Biochemical Indicators of... Mar 2015We examined whether the levels of oxidative stress biomarkers measured in blood reflect the tissue redox status. Data from studies that measured redox biomarkers in... (Review)
Review
We examined whether the levels of oxidative stress biomarkers measured in blood reflect the tissue redox status. Data from studies that measured redox biomarkers in blood, heart, liver, kidney and skeletal muscle were analyzed. In seven out of nine investigated redox biomarkers (malondialdehyde, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, vitamin C and E) there was generally good qualitative and quantitative agreement between the blood and tissues. In contrast, oxidized glutathione and the reduced to oxidized glutathione ratio showed poor agreement between the blood and tissues. This study suggests that most redox biomarkers measured in blood adequately reflect tissue redox status.
Topics: Animals; Biomarkers; Humans; Kidney; Liver; Muscle, Skeletal; Myocardium; Oxidation-Reduction; Oxidative Stress; Species Specificity
PubMed: 25582635
DOI: 10.3109/1354750X.2014.1002807 -
BMC Cardiovascular Disorders Jul 2023The purpose of this meta-analysis is to evaluate the role of high-intensity statin pretreatment on coronary microvascular dysfunction in patients with coronary heart... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this meta-analysis is to evaluate the role of high-intensity statin pretreatment on coronary microvascular dysfunction in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI).
METHODS
PubMed, Cochrane, and Embase were searched. This meta-analysis selection included randomized controlled trials (RCTs), involving high-intensity statin pretreatment as active treatment, and measurement of thrombolysis in myocardial infarction (TIMI), myocardial blush grade (MBG) or index of microvascular resistance (IMR) in coronary heart disease (CHD) patients undergoing PCI. I test was used to evaluate heterogeneity. Pooled effects of continuous variables were reported as Standard mean difference (SMD) and 95% confidence intervals (CI). Pooled effects of discontinuous variables were reported as risk ratios (RR) and 95% confidence intervals (CI). Random-effect or fix-effect meta-analyses were performed. The Benefit was further examined based on clinical characteristics including diagnosis and statin type by using subgroup analyses. Publication bias was examined by quantitative Egger's test and funnel plot. We performed sensitivity analyses to examine the robustness of pooled effects.
RESULTS
Twenty RCTs were enrolled. The data on TIMI < 3 was reported in 18 studies. Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI after PCI (RR = 0.62, 95%CI: 0.50 to 0.78, P < 0.0001). The data on MBG < 2 was reported in 3 studies. The rate of MBG < 2 was not different between groups (RR = 1.29, 95% CI: 0.87 to 1.93, P = 0.21). The data on IMR was reported in 2 studies. High-dose statin pretreatment significantly improved IMR after PCI comparing with non-high-dose statin (SMD = -0.94, 95% CI: -1.47 to -0.42, P = 0.0004). There were no significant between-subgroup differences in subgroups based on statin type and diagnosis. Publication bias was not indicated by using quantitative Egger's test (P = 0.97) and funnel plot. Sensitivity analyses confirmed the robustness of these findings.
CONCLUSIONS
Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI and IMR after PCI. In the future, RCTs with high quality and large samples are needed to test these endpoints.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Ischemia; Myocardial Infarction; Myocardium; Odds Ratio
PubMed: 37488501
DOI: 10.1186/s12872-023-03402-9 -
The Cochrane Database of Systematic... Jan 2015Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum® is a patented homeopathic medicine that is made from a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum® is a patented homeopathic medicine that is made from a 1% solution of wild duck heart and liver extract, which is then serially diluted 200 times with water and alcohol.
OBJECTIVES
To determine whether homeopathic Oscillococcinum® is more effective than placebo in the prevention and/or treatment of influenza and influenza-like illness in adults or children.
SEARCH METHODS
We searched CENTRAL (2014, Issue 8), MEDLINE (1966 to August week 4, 2014), MEDLINE In-Process & Other Non-Indexed Citations (4 September 2014), AMED (2006 to September 2014), Web of Science (1985 to September 2014), LILACS (1985 to September 2014) and EMBASE (1980 to September 2014). We contacted the manufacturers of Oscillococcinum® for information on further trials.
SELECTION CRITERIA
Randomised, placebo-controlled trials of Oscillococcinum® in the prevention and/or treatment of influenza and influenza-like illness in adults or children.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data and assessed risk of bias in the eligible trials.
MAIN RESULTS
No new trials were included in this 2014 update. We included six studies: two prophylaxis trials (327 young to middle-aged adults in Russia) and four treatment trials (1196 teenagers and adults in France and Germany). The overall standard of trial reporting was poor and hence many important methodological aspects of the trials had unclear risk of bias. There was no statistically significant difference between the effects of Oscillococcinum® and placebo in the prevention of influenza-like illness: risk ratio (RR) 0.48, 95% confidence interval (CI) 0.17 to 1.34, P value = 0.16. Two treatment trials (judged as 'low quality') reported sufficient information to allow full data extraction: 48 hours after commencing treatment, there was an absolute risk reduction of 7.7% in the frequency of symptom relief with Oscillococcinum® compared with that of placebo (risk difference (RD) 0.077, 95% CI 0.03 to 0.12); the RR was 1.86 (95% CI 1.27 to 2.73; P value = 0.001). A significant but lesser effect was observed at three days (RR 1.27, 95% CI 1.03 to 1.56; P value = 0.03), and no significant difference between the groups was noted at four days (RR 1.11, 95% CI 0.98 to 1.27; P value = 0.10) or at five days (RR 1.06, 95% CI 0.96 to 1.16; P value = 0.25). One of the six studies reported one patient who suffered an adverse effect (headache) from taking Oscillococcinum®.
AUTHORS' CONCLUSIONS
There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum® in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum® could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum®.
Topics: Animals; Ducks; Homeopathy; Humans; Influenza Vaccines; Influenza, Human; Liver Extracts; Myocardium; Randomized Controlled Trials as Topic; Syndrome; Tissue Extracts
PubMed: 25629583
DOI: 10.1002/14651858.CD001957.pub6 -
Physiology & Behavior Aug 2019We performed a systematic review and meta-analysis to determine if hypoxic conditioning, compared to similar training near sea level, maximizes body mass loss and... (Meta-Analysis)
Meta-Analysis Review
Additive stress of normobaric hypoxic conditioning to improve body mass loss and cardiometabolic markers in individuals with overweight or obesity: A systematic review and meta-analysis.
We performed a systematic review and meta-analysis to determine if hypoxic conditioning, compared to similar training near sea level, maximizes body mass loss and further improves cardiometabolic markers in overweight and obese individuals. A systematic search of PubMed, Web of Science and the Cochrane Library databases (up to January 2019) was performed. This analysis included randomized controlled trials with humans with overweight or obesity assessing the effects of HC on body mass loss or cardiometabolic markers. A subgroup analysis was performed to examine if HC effects differed between individuals with overweight or obesity. 13 articles (336 participants) qualified for inclusion. HC significantly decreased body mass (p = .01), fat mass (p = .04), waist/hip ratio (p < .001), waist (p < .001), LDL (p = .01), diastolic (p < .01) and systolic blood pressure (p < .01) with these effects not being larger than equivalent normoxic interventions. There were trends towards higher triglycerides decrement (p = .06) and higher muscle mass gain in hypoxic (p = .08) compared with normoxic condition. Also, the two BMI categories displayed no difference in the magnitude of the responses. Compared to normoxic equivalent, HC provides greater reductions in triglycerides and greater muscle growth, while body mass changes are similar. In addition, HC responses were essentially similar between individuals with overweight or obesity.
Topics: Biomarkers; Health Status; Humans; Hypoxia; Myocardium; Obesity; Overweight; Physical Conditioning, Human; Stress, Physiological; Weight Loss
PubMed: 31047948
DOI: 10.1016/j.physbeh.2019.04.027