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Congenital heart disease (CHD) is a major cause of infant mortality and morbidity, with growing interest in the role of environmental factors in its etiology. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has been implicated in the development of CHD. This study aimed to investigate the effects of DEHP exposure on fetal heart development in mice. Pregnant mice exposed to DEHP exhibited increased fetal malformations, decreased fetal weight, and reduced crown-rump length.f Transcriptomic analysis revealed the downregulation of genes involved in aerobic respiration and mitochondrial ATP synthesis. Functional assays demonstrated reduced mitochondrial respiration, decreased ATP production, elevated reactive oxygen species levels, and lowered mitochondrial membrane potential in DEHP-exposed fetal cardiomyocytes. These findings underscore the detrimental effects of DEHP on fetal cardiac health and provide insights into the molecular mechanisms underlying DEHP-induced CHD. Understanding these mechanisms is crucial for developing preventive strategies against environmental toxicants that affect fetal cardiac development. [ABSTRACT FROM AUTHOR]

Background: This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome. Methods: This study enrolled 13,119 participants aged 40–79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome. Results: The study participants had an average age of 56.06 years (95% CI: 55.76–56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50–980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70–0.97), hypertension (OR: 0.83, 95% CI: 0.70–0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67–0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome. Conclusion: The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Half of patients with heart failure are presented with preserved ejection fraction (HFpEF). The pathophysiology of these patients is complex, but increased left ventricular (LV) stiffness has been proven to play a key role. However, the application of this parameter is limited due to the requirement for invasive catheterization for its measurement. With advances in ultrasound technology, significant progress has been made in the noninvasive assessment of LV chamber or myocardial stiffness using echocardiography. Therefore, this review aims to summarize the pathophysiological mechanisms, correlations with invasive LV stiffness constants, applications in different populations, as well as the limitations of echocardiography‐derived indices for the assessment of both LV chamber and myocardial stiffness. Indices of LV chamber stiffness, such as the ratio of E/e' divided by left ventricular end‐diastolic volume (E/e'/LVEDV), the ratio of E/SRe (early diastolic strain rates)/LVEDV, and diastolic pressure‐volume quotient (DPVQ), are derived from the relationship between echocardiographic parameters of LV filling pressure (LVFP) and LV size. However, these methods are surrogate and lumped measurements, relying on E/e' or E/SRe for evaluating LVFP. The limitations of E/e' or E/SRe in the assessment of LVFP may contribute to the moderate correlation between E/e'/LVEDV or E/SRe/LVEDV and LV stiffness constants. Even the most validated measurement (DPVQ) is considered unreliable in individual patients. In comparison to E/e'/LVEDV and E/SRe/LVEDV, indices like time‐velocity integral (TVI) measurements of pulmonary venous and transmitral flows may demonstrate better performance in assessing LV chamber stiffness, as evidenced by their higher correlation with LV stiffness constants. However, only one study has been conducted on the exploration and application of TVI in the literature, and the accuracy of assessing LV chamber stiffness remains to be confirmed. Regarding echocardiographic indices for LV myocardial stiffness evaluation, parameters such as epicardial movement index (EMI)/ diastolic wall strain (DWS), intrinsic velocity propagation of myocardial stretch (iVP), and shear wave imaging (SWI) have been proposed. While the alteration of DWS and its predictive value for adverse outcomes in various populations have been widely validated, it has been found that DWS may be better considered as an overall marker of cardiac function performance rather than pure myocardial stiffness. Although the effectiveness of iVP and SWI in assessing left ventricular myocardial stiffness has been demonstrated in animal models and clinical studies, both indices have their limitations. Overall, it seems that currently no echocardiography‐derived indices can reliably and accurately assess LV stiffness, despite the development of several parameters. Therefore, a comprehensive evaluation of LV stiffness using all available parameters may be more accurate and enable earlier detection of alterations in LV stiffness. [ABSTRACT FROM AUTHOR]

Backgrounds: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. Aims and methods: We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. Results: A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. Conclusion: Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation. [ABSTRACT FROM AUTHOR]

Background: Isolated Prevotella intermedia, a rare gram-negative, rod-shaped, anaerobic bacterium, is rarely detected in clinical practice. It has been associated with infections of the oral cavity and female genital tract, but has never been detected in cerebrospinal fluid (CSF) of patients in China. Accurate detection of causative pathogens is still an arduous task owing to the difficult conditions of anaerobic bacterial culture. Isolated Prevotella intermedia can be detected by metagenomic next generation sequencing (mNGS) of the CSF. Correct diagnosis and antibiotic treatment can help patients avoid life-threatening events. Case presentation: Herein, we describe the case of a 64-year-old Chinese woman who presented with typical features of meningoencephalitis. Routine CSF culture failed to identify the causative pathogen. Isolated Prevotella intermedia was detected by mNGS, and the patient was treated with antibacterial agents including ceftriaxone, vancomycin, moxifloxacin, meropenem, metronidazole, and linezolid. The patient underwent surgical treatment for abscess of left frontal parietal lobe, which was observed on magnetic resonance imaging (MRI) and was suspected to be caused by Prevotella intermedia. It was further confirmed that it was a secondary infection from the oral cavity, and the possible etiology might have been dental surgery. Treatment was rendered to the patient based on metagenomic test result, and her condition improved after two months. Conclusions: This case highlights the role of mNGS in accurate diagnosis of patients with central nervous system infection. In particular, mNGS can be used to identify rare pathogens and confirm the diagnosis in patients with unknown etiology. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a rare and severe condition characterized by chamber dilation and impaired contraction of the left ventricle. It constitutes a fundamental etiology for profound heart failure and abrupt cardiac demise, rendering it a prominent clinical indication for heart transplantation (HTx) among both adult and pediatric populations. DCM arises from various etiologies, including genetic variants, epigenetic disorders, infectious insults, autoimmune diseases, and cardiac conduction abnormalities. The maintenance of cardiac function involves two distinct types of immune cells: resident immune cells and recruited immune cells. Resident immune cells play a crucial role in establishing a harmonious microenvironment within the cardiac tissue. Nevertheless, in response to injury, cardiomyocytes initiate a cytokine cascade that attracts peripheral immune cells, thus perturbing this intricate equilibrium and actively participating in the initiation and pathological remodeling of dilated cardiomyopathy (DCM), particularly during the progression of myocardial fibrosis. Additionally, immune cells assume a pivotal role in orchestrating the inflammatory processes, which are intimately linked to the prognosis of DCM. Consequently, understanding the molecular role of various immune cells and their regulation mechanisms would provide an emerging era for managing DCM. In this review, we provide a summary of the most recent advancements in our understanding of the molecular mechanisms of immune cells in DCM. Additionally, we evaluate the effectiveness and limitations of immunotherapy approaches for the treatment of DCM, with the aim of optimizing future immunotherapeutic strategies for this condition. [ABSTRACT FROM AUTHOR]

Background: The maturation of cardiomyocytes is a rapidly evolving area of research within the field of cardiovascular medicine. Understanding the molecular mechanisms underlying cardiomyocyte maturation is essential to advancing our knowledge of the underlying causes of cardiovascular disease. Impaired maturation can lead to the development of cardiomyopathy, particularly dilated cardiomyopathy (DCM). Recent studies have confirmed the involvement of the ACTN2 and RYR2 genes in the maturation process, facilitating the functional maturation of the sarcomere and calcium handling. Defective sarcomere and electrophysiological maturation have been linked to severe forms of cardiomyopathy. This report presents a rare case of DCM with myocardial non-compaction, probably resulting from allelic collapse of both the ACTN2 and RYR2 genes. Case Presentation: The proband in this case was a four-year-old male child who presented with a recurrent and aggressive reduction in activity tolerance, decreased ingestion volume, and profuse sweating. Electrocardiography revealed significant ST-T segment depression (II, III, aVF V3-V6 ST segment depression >0.05 mV with inverted T-waves). Echocardiography showed an enlarged left ventricle and marked myocardial non-compaction. Cardiac magnetic resonance imaging revealed increased left ventricular trabeculae, an enlarged left ventricle, and a reduced ejection fraction. Whole exome sequencing revealed a restricted genomic depletion in the 1q43 region (chr1:236,686,454-237,833,988/Hg38), encompassing the coding genes ACTN2, MTR, and RYR2. The identified variant resulted in heterozygous variations in these three genes, with the ACTN2 g.236,686,454-236,764,631_del and RYR2 g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. The patient was finally diagnosed with DCM and left ventricular myocardial non-compaction. Conclusions: This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the ACTN2 and RYR2 genes. This case provides the first human validation of the critical role of cardiomyocyte maturation in maintaining cardiac function and stability and confirms the key findings of previous experimental research conducted by our group. This report emphasizes the connection between genes involved in regulating the maturation of cardiomyocytes and the development of cardiomyopathy. [ABSTRACT FROM AUTHOR]

The article in Neurology India discusses a rare case of carotid artery stenting-induced neurogenic orthostatic hypotension (nOH) due to carotid sinus hypersensitivity (CSH). An 80-year-old man developed symptoms of dizziness, unstable gait, and amaurosis fugax after undergoing carotid artery stenting. The patient's blood pressure and heart rate showed significant changes in different positions, confirming the diagnosis of nOH. Treatment with fluid infusion and avoiding prolonged standing helped alleviate the symptoms. The study was approved by the Ethics Committee of the Municipal Hospital Affiliated to the Medical School of Taizhou University and was supported by funding from Traditional Chinese Medicine Health Science and Technology Plan Project of Zhejiang Province, China. [Extracted from the article]

Recent developments in ultrafine bubble generation have opened up new possibilities for applications in various fields. Herein, we investigated how substances in water affect the size distribution and stability of microbubbles generated by a common nanobubble generator. By combining light scattering techniques with optical microscopy and high-speed imaging, we were able to track the evolution of microbubbles over time during and after bubble generation. Our results showed that air injection generated a higher number of microbubbles (<10 μ m) than CO2 injection. Increasing detergent concentration led to a rapid increase in the number of microbubbles generated by both air and CO2 injection and the intensity signal detected by dynamic light scattering (DLS) slightly increased. This suggested that surface-active molecules may inhibit the growth and coalescence of bubbles. In contrast, we found that salts (NaCl and Na2CO3) in water did not significantly affect the number or size distribution of bubbles. Interestingly, the presence of oil in water increased the intensity signal and we observed that the bubbles were coated with an oil layer. This may contribute to the stability of bubbles. Overall, our study sheds light on the effects of common impurities on bubble generation and provides insights for analyzing dispersed bubbles in bulk. [ABSTRACT FROM AUTHOR]

Background: Among all fetal heart block patients, > 50% cases are associated with maternal autoimmune diseases, and such patients should receive treatment. However, nearly half of fetal heart block cases involve a mother with negative results following autoimmune antibody screening. A few studies have reported long QT syndrome (LQTS) can also present as a severe fetal bradycardia, which does not respond to fetal treatment. Herein, we reported a rare case of an infant who presented with high-degree autoimmune-mediated fetal atrioventricular block (AVB) with LQTS induced by a novel KCNH2 variant. This case led us to review our prenatal therapeutic strategy. Case presentation: A 1-year-old boy presented to our heart center having experienced syncope 5 times in the past year. He had previously presented with fetal bradycardia during the fetal stage from 27 + 3 gestational weeks. The fetal echocardiography demonstrated AVB (2:1 transmission). As the maternal autoimmune antibody results were positive, his mother had received dexamethasone treatment during pregnancy; subsequently, the fetal AVB had changed from 2:1 to 4:3 transmission with elevated ventricular beating rates. However, this patient was identified to have complete AVB after birth. The initial electrocardiogram and Holter measurements at hospital administration showed complete AVB, pleomorphic ventricular tachycardia, a prolonged QT interval (QT = 602 ms, corrected QT = 538 ms), and wide and deep inverted T-waves. Meanwhile, torsades de pointes could be observed in several transit ventricular tachycardias based on Holter monitoring review. Genetic testing revealed KCNH2 c.2483G > A variant–induced LQTS. An implantable cardioverter defibrillator device and permanent pacemaker were both considered as therapeutic alternations; his parents ultimately accepted the implantation of a permanent pacemaker. Conclusions: For fetuses with autoimmune-mediated AVB, intrauterine treatment should still be pursued immediately. However, once the treatment outcomes are deemed unacceptable or unexpected, other genetic variant–related channelopathies should be highly suspected. If the fetus lacks a positive family history, fetal genetic testing should be recommended to improve the prognosis of such patients by introducing integrative therapeutic strategies between the prenatal and postnatal phases. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a life-threatening condition that induce tens of million death each year, yet early diagnosis remains a formidable challenge. Many studies have focused on the diagnostic accuracy of microRNAs (miRNAs) for sepsis in recent years, particularly miR-155-5p, miR-21, miR-223-3p, miR-146a, and miR-125a. Thus, we conducted this meta-analysis to explore if miRNAs may be used as a biomarker for sepsis detection. Methods: We searched PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure through May 12, 2022. This meta-analysis was conducted using Meta-disc 1.4 and STATA 15.1 in a fixed/random-effect model. Results: The analysis included a total of 50 relevant studies. The overall performance of total miRNAs detection was: pooled sensitivity, 0.76 (95% confidence interval [CI], 0.75 to 0.77); pooled specificity, 0.77 (95%CI, 0.75 to 0.78); and area under the summary receiver operating characteristic curves value (SROC), 0.86. The subgroup analysis suggested that detection in miR-155-5p group had the highest area under the curve (AUC) of SROC among all miRNAs: pooled sensitivity, 0.71 (95%CI, 0.67 to 0.75); pooled specificity, 0.82 (95%CI, 0.76 to 0.86); and SROC, 0.85. MiR-21, miR-223-3p, miR-146a, and miR-125a had SROC values of 0.67, 0.78, 0.69, and 0.74, respectively. The specimen type was found to be a source of heterogeneity in the meta-regression study. The SROC of serum was higher than that of plasma (0.87 and 0.83, respectively). Conclusions: Our meta-analysis revealed that miRNAs, specifically miR-155-5p, could be useful biomarkers for detecting sepsis. A clinical serum specimen is also indicated for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Background: Coronary artery aneurysms (CAA) persistence prediction is critical in evaluating Kawasaki disease (KD). This study established a nomogram prediction system based on potential risk factors for assessing the risk of CAA persistence in a contemporary cohort of patients with KD. Methods: This cohort comprised 105 patients with KD who had been diagnosed with CAA during the acute or subacute phase by echocardiography. The follow-up duration was at least 1 year. The clinical and laboratory parameters were compared between the CAA regression and persistence groups. Multivariable logistic regression analysis was used to identify the independent risk factors for CAA persistence, which were subsequently used to build the nomogram predictive model. Decision curve analysis was used to assess the net benefits of different nomogram scores. Results: Of these patients with CAA, 27.6% of patients presented with persistent lesions. The incidences of CAA persistence were 14.1%, 81.3%, and 100.0% in patients with small, medium, and large aneurysms, respectively. The ratio of neutrophils to lymphocytes, γ-GT, and CAA size at diagnosis were considered as the independent risk factors for CAA persistence in patients with KD. The nomogram predictive models yielded a high capability in predicting CAA persistence, based on either univariable or multivariable analyses-identified parameters, compared with using CAA size as a single predictor. Conclusion: The initial ratio of neutrophils to lymphocytes, γ-GT, and CAA size were the independent risk factors for CAA persistence in patients with KD. Nomogram scores could help elevate predictive efficacy in detecting CAA persistence. [ABSTRACT FROM AUTHOR]

Pipeline transport is commonly used in the oil sand industry to convey crushed oil sand ores and tailings. Bitumen residues in the oil sand tailings can be a threat to the environment that separating them from tailings before disposal is crucial. However, low bitumen concentration in the tailing slurry and the complex transport characteristics of the four-phase mixture make the process difficult. This study establishes an Eulerian–Eulerian (E–E) computational fluid dynamics model for an industrial-scale oil sand tailings pipeline. A comprehensive sensitivity analysis was conducted on the selection of carrier-solid and solid-bitumen drag models. The combination of small and large particle sizes (i.e., 75 and 700 μm) and bitumen droplet size (i.e., 400 μm) provided good agreement with field data in velocity profiles and pressure drop. The validated model was subsequently extended to investigate the influence of the secondary phase (i.e., bitumen droplets and bubbles) on flow characteristics in a tailing pipeline. The investigation covered a range of bitumen droplet size (100–400 μm), bitumen fraction (0.0025–0.1), bubble size (5–1000 μm), and bubble fraction (0.0025–0.3) and their influences on the velocity, solids, and bitumen distribution are revealed. For an optimum bubble size of 500 μm, a maximum recovery of 59% from the top 50% and 83% from the top 75% of the pipe cross section was obtained. The present study demonstrates the preferential distribution of bitumen and provides valuable insight into bitumen recovery from an industrial-scale tailing pipeline. [ABSTRACT FROM AUTHOR]

Background: Peripheral gangrene is rarely documented as a possible complication of Kawasaki disease (KD). There are many causes of peripheral gangrene, and the common cause is in situ thrombosis or embolism. Most cases are reported to have regrettable outcomes (amputation or necrotic shedding). Herein, we report the successful management of KD complicated by peripheral artery thrombosis in an older Chinese boy, and a review of all cases of peripheral gangrene in KD in the literature. Case presentation: We found that most of the children with this complication were under 1 year old, had a heavy inflammatory response combined with the use of cortisol and immunoglobulin, and most children had coronary artery lesions. In addition, Peripheral gangrene mainly occurred in the subacute or chronic stage, and the prognosis is poor. Conclusions: In the presence of high risk factors, we consider it is necessary to monitor coagulation function and administer prophylactic anticoagulation therapy. When peripheral artery thrombosis or embolism occur, heparin and prostaglandins can be used for treatment. [ABSTRACT FROM AUTHOR]

Background: PRKAG2 cardiac syndrome is a rare autosomal dominant genetic disorder caused by a PRKAG2 gene variant. There are several major adverse cardiac presentations, including hypertrophic cardiomyopathy (HCM) and life‐threatening arrhythmia. Two cases with pathogenic variants in the PRKAG2 gene are reported here who presents different cardiac phenotypes. Methods: Exome sequencing and variant analysis of PRKAG2 were performed to obtain genetic data, and clinical characteristics were determined. Results: The first proband was a 9‐month‐old female infant (Case 1), and was identified with severe DCM and resistant heart failure. The second proband was a 10‐year‐old female infant (Case 2), and presented with HCM and ventricular preexcitation. Exome sequencing identified a de novo c.425C > T (p.T142I) heterozygous variant in the PRKAG2 gene for Case 1, and a c.869A > T (p.K290I) for Case 2. The mutated sites in the protein were labeled and identified as p.K290 in the CBS domain and p.T142 in the non‐CBS domain. Differences in the molecular functions of CBS and non‐CBS domains have not been resolved, and variants might lead to the different cardiomyopathy phenotypes. Single‐cell RNA analysis demonstrated similar expression levels of PRKAG2 in cardiomyocytes and conductive tissues. These results suggest that the arrhythmia induced by the PRKAG2 variant was the primary change, and not secondary to cardiomyopathy. Conclusion: In summary, this is the first case report to describe a DCM phenotype with early onset in patients possessing a PRKAG2 c.425C > T (p.T142I) pathogenic variant. Our results aid in understanding the molecular function of non‐CBS variants in terms of the disordered sequence of transcripts. Moreover, we used scRNA‐seq to show that electrically conductive cells express a higher level of PRKAG2 than do cardiomyocytes. Therefore, variants in PRKAG2 are expected to also alter the biological function of the conduction system. [ABSTRACT FROM AUTHOR]

Background: Whether high D-dimer level before treatment has any impact on poor outcomes in patients with community-associated pneumonia (CAP) remains unclear. Therefore, we conducted the first meta-analysis focusing specifically on prognostic value of high D-dimer level before treatment in CAP patients. Methods: Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center were searched up to the end of March 2021. Randomized clinical trials (RCT) and observational studies were included to demonstrate the association between the level of D-dimer and clinical outcomes. Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation. Data were analyzed using STATA 14.0 to complete meta and network analysis. Main outcomes and measures: Besides d-dimer levels in CAP patients with poor outcomes, we also analyzed proportion of patients with or without poor outcomes correctly classified by the d-dimer levels as being at high or low risk. The poor outcome includes severe CAP, death, pulmonary embolism (PE) and invasive mechanical ventilators. Results: 32 studies with a total of 9,593 patients were eventually included. Pooled effect size (ES) suggested that d-dimer level was significantly higher in severe CAP patients than non-severe CAP patients with great heterogeneity (SMD = 1.21 95%CI 0.87–1.56, I2 = 86.8% p = 0.000). D-dimer level was significantly elevated in non-survivors compared to survivors with CAP (SMD = 1.22 95%CI 0.67–1.77, I2 = 85.1% p = 0.000). Prognostic value of d-dimer for pulmonary embolism (PE) was proved by hierarchical summary receiver operating characteristic curve (HSROC) with good summary sensitivity (0.74, 95%CI, 0.50–0.89) and summary specificity (0.82, 95%CI, 0.41–0.97). Network meta-analysis suggested that there was a significant elevation of d-dimer levels in CAP patients with poor outcome than general CAP patients but d-dimer levels weren't significantly different among poor outcomes. Conclusion: The prognostic ability of d-dimer among patients with CAP appeared to be good at correctly identifying high-risk populations of poor outcomes, suggesting potential for clinical utility in patients with CAP. [ABSTRACT FROM AUTHOR]

Background: Intravenous immunoglobulin (IVIG) resistance prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigate the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD and to assess whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance. Methods: A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between the IVIG-response group (n = 708) and the IVIG-resistance group (n = 115). Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. Results: ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ − 2.57 (AUC: 0.705, 95 %CI: 0.672–0.736), ALB ≤ 33.0 g/L (AUC: 0.659, 95 %CI: 0.626–0.692), and TBil ≥ 16.0µmol/L (AUC: 0.626, 95 %CI: 0.592–0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226 and 0.914; 0.374, 0.850, 0.289 and 0.893; 0.269, 0.941, 0.425 and 0.888, respectively. Conclusions: A higher ALBI was an independent risk factor for IVIG resistance in KD. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance. [ABSTRACT FROM AUTHOR]

Background: Intravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial IVIG resistance and repeated IVIG resistance in KD. Methods: A total of 385 KD patients were prospectively recruited between April 2015 and May 2019. Coagulation and other profiles were evaluated between the IVIG‐responsive and IVIG‐resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess the validity of coagulation profiles in predicting both initial IVIG resistance and repeated IVIG resistance. Results: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen degradation products (FDPs), and D‐dimer were significantly increased in the initial IVIG‐resistant group with antithrombin III (ATIII) and thrombin time (TT) significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG‐resistant patients. Multivariate logistic regression analysis showed that PT, APTT, D‐dimer, and ATIII were independent risk factors for predicting initial IVIG resistance and ATIII for predicting repeated IVIG‐resistant patients with KD. PT, APTT, D‐dimer, and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/L, and 89.5% yielded sensitivities of 73%, 32%, 71%, and 81%, and specificities of 55%, 88%, 62%, and 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%. Conclusions: KD patients who have hypercoagulation during the acute phase might be at higher risk of developing IVIG resistance. [ABSTRACT FROM AUTHOR]

Background: Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAL. Although most of the current studies have shown a certain correlation between CAL and IVIG resistance, the conclusions are not completely consistent. Thus, we performed this meta-analysis to evaluate the association between IVIG resistance and CAL in KD. Methods: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through April 21, 2020 were searched to detect relevant studies. Data analysis was performed with STATA 15.1. Results: A total of 53 relevant studies were eligible to this analysis, including 30312 KD patients, of which 4750 were IVIG resistance and 25562 were responders. There was a significant difference found between IVIG resistance and IVIG response groups in the incidence of CAL (P < 0.001, odds ratio (OR), 3.89; 95% confidence interval (CI) (3.18, 4.75)). The heterogeneity test results showed that the I2 value was 74.8%. The meta-regression analysis showed that the study regions might be the sources of heterogeneity. The subgroup analysis suggested that the incidence of CAL in the IVIG resistance group was still higher than that in the IVIG response group under different regions, IVIG resistance diagnostic criteria, CAL diagnostic criteria, and study types. Meanwhile, the sensitivity analysis did not find any significant impact from every single study. Conclusions: This is the first meta-analysis to reveal the incidence of CAL was associated with IVIG resistance in KD patients. Further well-designed studies with uniform criteria are needed to evaluate the incidence of CAL in IVIG resistant patients. [ABSTRACT FROM AUTHOR]

Background: Intravenous immunoglobulin (IVIG) resistance prediction is one pivotal topic of interests in Kawasaki disease (KD). This study aimed to prospectively investigated the value of C-reactive protein-to-albumin (CAR) in predicting both initial and repeated IVIG resistance in patients with KD, and to test the hypothesis that CAR was more valuable or accurate than either C-reactive protein (CRP) or albumin (ALB) alone in IVIG resistance prediction. Method: A prospective cohort study involving 550 patients with KD was conducted. The clinical and laboratory data were compared between IVIG-response group and IVIG-resistance group. Multivariate logistic regression analysis was performed to identify the independent risk factors of initial/repeated IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of CAR, CRP and ALB in predicting both initial and repeated IVIG resistance. Results: CAR was significantly higher in IVIG non-responders and was identified as independent risk factor for both initial and repeated IVIG resistance in KD. The best cut-off value of CAR for initial and repeated IVIG resistance prediction was 2.07 and 3.34, with a corresponding sensitivity of 0.610 and 0.548, a specificity of 0.552 and 0.813, respectively. The value of CAR was not better than either CRP or ALB alone for both initial and repeated IVIG resistance prediction. Conclusion: A higher CAR was an independent risk factor for both initial and repeated IVIG resistance. However, similar with that of CRP or ALB, the predictive value of CAR was not good enough for both initial and repeated IVIG resistance prediction in KD. [ABSTRACT FROM AUTHOR]

Myh7 is a classic biomarker for cardiac remodeling and a potential target to attenuate cardiomyocyte (CM) hypertrophy. This study aimed to identify the dominant function of Myh7 after birth and determine whether its removal would affect CM maturation or contribute to reversal of pathological hypertrophy phenotypes. The CASAAV (CRISPR/Cas9-AAV9-based somatic mutagenesis) technique was used to deplete Myh6 and Myh7, and an AAV dosage of 5 × 109 vg/g was used to generate a mosaic CM depletion model to explore the function of Myh7 in adulthood. CM hypertrophy was induced by transverse aortic constriction (TAC) in Rosa26Cas9-P2A-GFP mice at postnatal day 28 (PND28). Heart function was measured by echocardiography. Isolated CMs and in situ imaging were used to analyze the structure and morphology of CM. We discovered that CASAAV successfully silenced Myh6 and Myh7 in CMs, and early depletion of Myh7 led to mild adulthood lethality. However, the Myh7 PND28-knockout mice had normal heart phenotype and function, with normal cellular size and normal organization of sarcomeres and T-tubules. The TAC mice also received AAV-Myh7-Cre to produce Myh7-knockout CMs, which were also of normal size, and echocardiography demonstrated a reversal of cardiac hypertrophy. In conclusion, Myh7 has a role during the maturation period but rarely functions in adulthood. Thus, the therapeutic time should exceed the period of maturation. These results confirm Myh7 as a potential therapeutic target and indicate that its inhibition could help reverse CM hypertrophy. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children. Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive. We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). Methods: We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017. Profiles of patients with neurological symptoms (group A, n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B, n = 512). Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance. Results: Neurological involvement was observed in 5.1% (80/1582) of patients with KD. The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%). Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD. The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B. However, neurological involvement was not an independent risk factor for IVIG resistance or CALs. Conclusion: Rates of neurological involvement were relatively low in patients with KD. Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden. Our results highlight the need for pediatricians to recognize KD with neurological involvement and the importance of standard IVIG therapy. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

To identify the risk factors of progression and persistence of small- and medium-sized coronary artery aneurysm (CAA) in a contemporary cohort of patients with Kawasaki disease (KD) and to determine the relationship between CAA progression and persistence. A total of 89 KD patients with small- and medium-sized CAA were prospectively enrolled. All patients were followed up at least for 2 years by serial echocardiography. Multivariate logistic regression analysis was conducted to evaluate independent risk factors for CAA progression and persistence. A total of 46 (51.7%) and 73 (82.0%) patients showed echocardiographic CAA regression by 1 month and 24 months of follow-up, respectively. CAA progression was documented in 12 (13.5%) patients during follow-up. The initial aneurysm size according to CAA classification (OR 0.089, 95% CI 0.013-0.634, P = 0.016) and CAA progression (OR 42.618, 95% CI 3.740-485.6, P = 0.003) were independently associated with CAA persistence. The number of involved coronary arteries (OR 0.223, 95% CI 0.065-0.767, P = 0.015) and lymphocyte proportion (OR 1.327, 95% CI 1.019-1.727, P = 0.040) were independently associated with CAA progression.Conclusion: Patients with KD and greater initial aneurysm size, CAA progression, more involved coronary arteries, and lower lymphocyte proportion may require intensive cardiac monitoring and adjuvant therapies.What is Known:• Long-term outcomes of patients with KD and CAA are primarily driven by the consequences of CAA regression and progression.• Regression and progression occurs more frequently in patients with small- and medium-sized CAAs, and less frequently for giant CAAs.What is New:• The CAA size at diagnosis, NCAI, and the proportion of lymphocytes are presumably associated with the small- and medium-sized CAA persistence or CAA progression.• The CAA progression was associated with CAA persistence. [ABSTRACT FROM AUTHOR]

Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is currently the most common acquired heart disease in children in many countries. Nevertheless, there is no single useful marker existing for predicting CAL of KD. Recently, many reports have noted that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be utilized as a biomarker to predict CAL. Thus, we perform a meta-analysis to ascertain the diagnostic value of NT-proBNP in detecting CAL of KD in the acute phase. PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure were searched to detect relevant publications. Finally, eight eligible studies were included. The overall diagnostic sensitivity and specificity were 0.84 (95% confidence interval [CI]: 0.78–0.89) and 0.71 (95% CI: 0.68–0.75), respectively. The area under the summary receiver operating characteristic curves value (SROC) curve was 0.8582 ± 0.0531. Moreover, the overall sensitivity and specificity across five studies adopted the threshold of approximately 900 ng/L were 0.82 (95% CI: 0.73–0.89) and 0.72 (95% CI: 0.68–0.76), respectively. SROC was 0.8868 ± 0.0486. This meta-analysis would be the first one to describe the role of NT-proBNP in detecting CAL of KD. We register this study with PROSPERO (CRD42019130083). [ABSTRACT FROM AUTHOR]

Background: In recent years, many studies focused on the association between the microRNAs (miRNAs) and the risk of systemic lupus erythematosus (SLE), especially miRNA-21 (miR-21). We aimed to investigate the role of circulating miRNAs, especially the miR-21, as a biomarker in detecting SLE. Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through Mar 3th, 2019. We performed this meta-analysis in a fixed/random-effect model using Meta-disc 1.4 and STATA 15.1. Results: A total of 17 relevant studies were eligible to analyze pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.71 (95% confidence interval [CI], 0.69 to 0.72); pooled specificity, 0.81 (95%CI, 0.79 to 0.83); and area under the summary receiver operating characteristic curves value (SROC), 0.8797. The miR-21 detection was: pooled sensitivity, 0.68 (95%CI, 0.62 to 0.74); pooled specificity, 0.77 (95%CI, 0.69 to 0.84); and SROC, 0.8281. The meta-regression analysis showed that the type of samples was the sources of heterogeneity. The subgroup analysis suggested that detection in plasma group had the largest AUC of SROC in all the subgroups: pooled sensitivity, 0.8 (95%CI, 0.78 to 0.82); pooled specificity, 0.83 (95%CI, 0.8 to 0.86); and SROC, 0.9068. Conclusions: Our meta-analysis demonstrated that circulating miRNAs might be potential novel biomarkers for detecting SLE, especially miR-21. Moreover, plasma is recommended as the clinical specimen for diagnostic detection. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is now the leading cause of acquired heart disease in children in developed countries. Intravenous immunoglobulin (IVIG) and aspirin were considered as the standard initial treatment of KD for decades. However, the optimal dose of aspirin has remained controversial. In recent years, many studies compared the efficacy of low-dose with high-dose aspirin in the acute phase of KD, but the results have not always been consistent. Therefore, we performed this meta-analysis to evaluate the efficacy of low-dose aspirin compared with high-dose for the initial treatment of KD. Methods: Studies related to aspirin therapy for KD were selected from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Google scholar through Mar 25th, 2019. Data were analyzed using STATA Version 15.1. Additionally, publication bias and sensitivity analysis were also performed by STATA version 15.1. Results: Six studies were included in our analysis of the rate of coronary artery lesion (CAL), five reports for IVIG-resistant KD (rKD), and four for the duration of fever and hospitalization. However, no significant differences were found between low-dose and high-dose aspirin groups in the incidence of CAL (risk ratio (RR), 0.85; 95%CI (0.63, 1.14); P = 0.28), the risk of rKD (RR, 1.39; 95%CI (1.00, 1.93); P = 0.05), and duration of fever and hospitalization (the mean standard deviation (SMD), 0.03; 95%CI (-0.16, 0.22); P = 0.78). Conclusion: Low-dose aspirin (3–5 mg·kg-1·d-1) may be as effective as the use of high-dose aspirin (≥30 mg·kg-1·d-1) for the initial treatment of KD. Further well-designed randomized clinical trials are needed to evaluate the efficacy of low-dose aspirin for the initial treatment of KD. [ABSTRACT FROM AUTHOR]

Backgrounds: Reducing toxicants transplacental rates could contribute to the prevention of congenital heart defects (CHDs). Placental P-glycoprotein (P-gp) plays a vital role in fetal toxicants exposure and subsequently affects the risk of toxicants-induced birth defects. However, data on the role of placental P-gp in decreasing toxicants-induced cardiac anomalies is extremely limited. This study aimed to explore the protective role of placental P-gp in reducing the risk of Di-(2-ethylhexyl)-phthalate (DEHP) induced cardiac anomalies in mice. Methods: The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 500mg/Kg DEHP group (n = 15), 3mg/Kg verapamil group (n = 10) and 500mg/Kg DEHP & 3mg/Kg verapamil group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from E6.5–14.5. Maternal weights were monitored every day and samples were collected at E15.5. HE staining was used to examine fetal cardiac malformations. Real-time quantitative PCR (RT-qPCR) and Western-Blot were applied to detect Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. The mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) was also determined using RT-qPCR. Results: Co-administration of verapamil and DEHP significantly elevated fetal cardiac malformation rates, in comparison with the DEHP group, the verapamil group and the vehicle group. Different phenotypes of cardiac anomalies, including septal defects and ventricular myocardium noncompaction, were noted both in the DEHP group and the DEHP & verapamil group. The ventricular myocardium noncompaction appeared to be more severe in the DEHP & verapamil group. Fetal cardiac PPARγ mRNA expression was notably increased and Gata4/Mef2c/Chf1 expression was markedly decreased in the DEHP & verapamil group. Conclusion: Placental P-gp inhibition enhances susceptibility to DEHP induced cardiac malformations in mice. [ABSTRACT FROM AUTHOR]

Background: Mitochondria are energy-producing structure of the cell and help to maintain redox environment. In cardiovascular disease, the number of mitochondrial DNA (mtDNA) will changes accordingly compare to normal condition. Some investigators ask whether it has a clear association between mtDNA and cardiovascular disease with its adverse events. Thus, we conduct the meta-analysis to assess the role of circulating mtDNA in evaluating cardiovascular disease. Methods: The meta-analysis was conducted in accordance with a predetermined protocol following the recommendations of Cochrane Handbook of Systematic Reviews. We searched the Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center to identify relevant studies up to the end of October 2017. Data were analyzed using STATA. Besides, publication bias and meta-regression analysis were also conducted. Results: We collected results from 5 articles for further analyses with 8,252 cases and 20,904 control. The normalized mtDNA copy number level is lower in cardiovascular disease (CVD) than the control groups with a pooled standard mean difference (SMD) of -0.36(95%CI,-0.65 to -0.08); The pooled odds ratio (OR) for CVD proportion associated with a 1-SD (standard deviation) decrease in mtDNA copy number level is 1.23 (95% CI,1.06–1.42); The OR for CVD patients with mtDNA copy number lower than median level is 1.88(95% CI,1.65–2.13); The OR for CVD patients with mtDNA copy number located in the lowest quartile part is 2.15(95% CI, 1.46–3.18); the OR between mtDNA copy number and the risk of sudden cardiac death (SCD) is 1.83(95% CI, 1.22–2.74). Conclusion: Although inter-study variability, the overall performance test of mtDNA for evaluating CVD and SCD revealed that the mtDNA copy number presented the potential to be a biomarker for CVD and SCD prediction. Given that, the fewer copies of mtDNA, the higher the risk of CVD. [ABSTRACT FROM AUTHOR]

Abstract: Accumulating evidence has suggested a link between maternal di‐(2‐ethylhexyl)‐phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250 mg kg–1 DEHP group (n = 15), 500 mg kg–1 DEHP group (n = 20) and 1 g kg–1 DEHP group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and samples were collected at E15.5. Hematoxylin and eosin staining was used to examine fetal cardiac malformations. Real‐time quantitative polymerase chain reaction and western blot were applied to detect peroxisome proliferator‐activated receptor (PPAR)α/PPARγ/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. Maternal DEHP exposure significantly decreased maternal body weight, fetal weight and placental weight, and remarkably elevated fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly include septal defects, ventricular myocardium noncompaction and cardiac hypoplasia. Higher doses DEHP (500 mg kg–1 and 1 g kg–1) could significantly decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARγ expression was upregulated. Maternal exposure to higher doses of DEHP could result in fetal cardiac development malformations in mice and it might have resulted from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) belong to a class of non-coding RNAs that regulate post-transcriptional gene expression during development and disease. Growing evidence indicates abundant miRNA expression changes and their important role in cardiac hypertrophy and failure. However, the role of miRNAs in fetal cardiac remodeling is little known. Here, we investigated the altered expression of fifteen miRNAs in rat fetal cardiac remodeling compared with adult cardiac remodeling. Among fifteen tested miRNAs, eleven and five miRNAs (miR-199a-5p, miR-214-3p, miR-155-3p, miR-155-5p and miR-499-5p) are significantly differentially expressed in fetal and adult cardiac remodeling, respectively. After comparison of miRNA expression in fetal and adult cardiac remodeling, we find that miRNA expression returns to the fetal level in adult cardiac failure and is activated in advance of the adult level in fetal failure. The current study highlights the contrary expression pattern between fetal and adult cardiac remodeling and that supports a novel potential therapeutic approach to treating heart failure. [ABSTRACT FROM AUTHOR]