KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter.

Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis.

BACKGROUND: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. METHODS AND RESULTS: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co-expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis-related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four-gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. CONCLUSION: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment.

The lncRNA GAS5 upregulates ANXA2 to mediate the macrophage inflammatory response during atherosclerosis development.

Inflammatory macrophages play a crucial role in atherosclerosis development. The long non-coding RNA growth arrest-specific 5 (GAS5) regulates THP-1 macrophage inflammation by sponging microRNAs. The purpose of this study was to investigate the regulatory mechanism of GAS5 in atherosclerosis development. GSE40231, GSE21545, and GSE28829 datasets from the Gene Expression Omnibus database were integrated after adjusting for batch effect. Differential analysis was performed on the integrated dataset and validated using the Genotype-Tissue Expression and GSE57691 datasets. Potential biological functions of GAS5 and annexin A2 (ANXA2) were identified using gene set enrichment analysis (GSEA). ssGSEA, CIBERSORTx, and ImmuCellAI algorithms were used to identify immune infiltration in plaque samples. GAS5 and ANXA2 expression levels in RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL) were measured by qRT-PCR and Western blot. Small interfering and short hairpin RNA were used to silence GAS5 expression. Plasmids of ANXA2 were used to establish ANXA2 overexpression. Apoptosis and inflammatory markers in macrophages were detected by Western blot. Aortic samples from APOE-/- mice were collected to validate the expression of GAS5 and ANXA2. GAS5 expression was significantly increased during atherosclerosis. GAS5 expression was positively correlated with macrophage activation and ANXA2 expression in plaques. Furthermore, ANXA2 upregulation was also related to the activation of macrophage. GSEA indicated similar biological functions for GAS5 and ANXA2 in plaques. Moreover, in vitro experiments showed that both GAS5 and ANXA2 contributed to macrophage apoptosis and inflammation. Rescue assays revealed that the inflammatory effects of GAS5 on macrophages were ANXA2-dependent. In vivo experiments confirmed the highly expression of Gas5 and Anxa2 in the plaque group. We identified the atherogenic roles of GAS5 and ANXA2 in the inflammatory response of macrophages. The inflammatory response in ox-LDL-treated macrophages was found to be mediated by GAS5-ANXA2 regulation, opening new avenues for atherosclerosis therapy.

A Journey of Challenges and Victories: A Bibliometric Worldview of Nanomedicine since the 21st Century.

Nanotechnology profoundly affects the advancement of medicine. Limitations in diagnosing and treating cancer and chronic diseases promote the growth of nanomedicine. However, there are very few analytical and descriptive studies regarding the trajectory of nanomedicine, key research powers, present research landscape, focal investigative points, and future outlooks. Herein, articles and reviews published in the Science Citation Index Expanded of Web of Science Core Collection from first January 2000 to 18th July 2023 are analyzed. Herein, a bibliometric visualization of publication trends, countries/regions, institutions, journals, research categories, themes, references, and keywords is produced and elaborated. Nanomedicine-related academic output is increasing since the COVID-19 pandemic, solidifying the uneven global distribution of research performance. While China leads in terms of publication quantity and has numerous highly productive institutions, the USA has advantages in academic impact, commercialization, and industrial value. Nanomedicine integrates with other disciplines, establishing interdisciplinary platforms, in which drug delivery and nanoparticles remain focal points. Current research focuses on integrating nanomedicine and cell ferroptosis induction in cancer immunotherapy. The keyword "burst testing" identifies promising research directions, including immunogenic cell death, chemodynamic therapy, tumor microenvironment, immunotherapy, and extracellular vesicles. The prospects, major challenges, and barriers to addressing these directions are discussed.

Genome-wide DNA methylation of lesional and peri-lesional skin in vitiligo: a comparative and integrated analysis of multi-omics in Chinese population.

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs (ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B, HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1). Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies.

Chronic kidney disease in the shadow of COVID-19: insights from the bibliometric analysis.

OBJECTIVE: This study aims to present the current status and frontiers of research on COVID-19 in relation to chronic kidney disease through bibliometric analysis and visualization. METHODS: Access to information through the Web of Science Core Collection, retrieved from December 2019 to May 2023. The bibliometric visualization of countries, institutions, and keywords was analyzed using VOSviewer. RESULTS: A total of 1038 publications are included. The global scientific community showed a high level of collaborative consensus. The three countries with the most publications are the USA, China, and the UK. The institution with the most publications is Harvard Medical School. The research frontier for 2020 is thrombosis, for 2021 is telemedicine, for 2022 is depression, and for 2019-2023 is the COVID-19 vaccines. CONCLUSIONS: This is the first bibliometric report to establish a link between COVID-19 and CKD. The USA, China, and some European countries and their institutions are major contributors to these publications. Thrombosis, telemedicine, depression, and COVID-19 vaccines are current hot topics in the field and have the potential to shape future research trends.

LncRNA GAS5 downregulates NLRP3 inflammasome activation-mediated pyroptosis in sepsis-induced myocardial injury by targeting SIRT3/AMPKα.

An increasing body of studies has demonstrated the significance of long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) in inflammation and myocardial injury in septic shock. This research aims to determine whether GAS5 contributes to the pathological development of sepsis-induced cardiac damage and NLRP3 inflammasome-mediated myocardial cell pyroptosis. Cecal ligation and puncture (CLP) surgery was used to cause septic shock in C57BL/6 wild-type mice. After CLP, inflammatory, pyroptosis parameters of myocardial tissue, survival rate, and Murine Sepsis Score (MSS) were assessed to evaluate the involvement of GAS5 in the mouse myocardial depression. To investigate GAS5's function in lipopolysaccharide (LPS) induced myocardial cell pyroptosis, gain- and loss-of-function experiments were conducted in vitro on HL-1 cells. Our findings indicated that CLP dramatically reduced survival rates, MSS, SIRT3 and p-AMPK expression, and activated the Nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome-mediated pyroptosis. The NF-κB and pyroptosis pathways were greatly elevated while SIRT3/p-AMPKα was dramatically decreased as a result of GAS5 being downregulated. Meanwhile, the regulatory effect could be suppressed by SIRT3 and AMPKα activator. Our observations supported the idea that GAS5 has a crucial protective impact against myocardial inflammation and pyroptosis in sepsis.

DNA methylation profiling and integrative multi-omics analysis of skin samples reveal important contribution of epigenetics and immune response in the pathogenesis of acne vulgaris.

The regulatory effect of DNA methylation on the pathogenesis of acne vulgaris is completely unknown. Herein we analyzed the DNA methylation profile in skin samples of acne vulgaris and further integrated it with gene expression profiles and single-cell RNA-sequencing data. Finally, 31,134 differentially methylated sites and 770 differentially methylated and expressed genes (DMEGs) were identified. The multi-omics analysis suggested the importance of DNA methylation in inflammation and immunity in acne. And DMEGs were verified in an external dataset and were closely related to early inflammatory acne. Additionally, we conducted experiments to verify the mRNA expression and DNA methylation level of DMEGs. This study supports the significant contribution of epigenetics to the pathogenesis of acne vulgaris and may provide new ideas for the molecular mechanisms of and potential therapeutic strategies for acne vulgaris.

Prevalence and risk factors of acne scars in patients with acne vulgaris.

BACKGROUND: Acne scar is a persistent complication of acne vulgaris. However, the prevalence and risk factors are still unclear. This study aimed to assess the global prevalence and risk factors of acne scars in patients with acne. MATERIALS AND METHODS: A systematic search of published studies in three databases was performed and the meta-analyses were conducted. RESULTS: Finally, we included 37 studies involving 24 649 acne patients. And, the pooled prevalence of acne scars in these patients was 47% (95% confidence interval [CI]: 38-56%). Besides, the differences in prevalence were observed based on the subgroup analysis for age, gender, acne severity, source of patients, and so on. Subsequently, we quantified the relationship of three risk factors with acne scars: male gender (odds ratio [OR]: 1.58, 95% CI: 1.19-2.09), positive family history of acne (OR: 2.73, 95% CI: 1.26-5.91), and acne severity (OR for moderate acne: 2.34, 95% CI: 1.54-3.57; OR for severe acne: 5.51, 95% CI: 2.45-12.41). CONCLUSION: Herein, we found that 47% of acne patients suffered from acne scars and identified three risk factors: male gender, positive family history of acne, and acne severity. In order to reduce acne scarring, attention and effective therapy early in the course of acne is important.

Acne and risk of mental disorders: A two-sample Mendelian randomization study based on large genome-wide association data.

Background: Despite a growing body of evidence that acne impacts mental disorders, the actual causality has not been established for the possible presence of recall bias and confounders in observational studies. Methods: We performed a two-sample Mendelian randomization (MR) analysis to evaluate the effect of acne on the risk of six common mental disorders, i.e., depression, anxiety, schizophrenia, obsessive-compulsive disorder (OCD), bipolar disorder, and post-traumatic stress disorder (PTSD). We acquired genetic instruments for assessing acne from the largest genome-wide association study (GWAS) of acne (N = 615,396) and collected summary statistics from the largest available GWAS for depression (N = 500,199), anxiety (N = 17,310), schizophrenia (N = 130,644), OCD (N = 9,725), bipolar disorder (N = 413,466), and PTSD (N = 174,659). Next, we performed the two-sample MR analysis using four methods: inverse-variance weighted method, MR-Egger, weighted median, and MR pleiotropy residual sum and outliers. Sensitivity analysis was also performed for heterogeneity and pleiotropy tests. Results: There was no evidence of a causal impact of acne on the risk of depression [odds ratio (OR): 1.002, p = 0.874], anxiety (OR: 0.961, p = 0.49), OCD (OR: 0.979, p = 0.741), bipolar disorder (OR: 0.972, p = 0.261), and PTSD (OR: 1.054, p = 0.069). Moreover, a mild protective effect of acne against schizophrenia was observed (OR: 0.944; p = 0.033). Conclusion: The increased prevalence of mental disorders observed in patients with acne in clinical practice was caused by modifiable factors, and was not a direct outcome of acne. Therefore, strategies targeting the elimination of potential factors and minimization of the occurrence of adverse mental events in acne should be implemented.

Aerobic exercise inhibits renal EMT by promoting irisin expression in SHR.

To determine the effect of aerobic exercise in different intensities on renal injury and epithelial-mesenchymal transformation (EMT) in the kidney of spontaneously hypertensive rats (SHR) and explore possible mechanisms, we subjected SHR to different levels of 14-week aerobic treadmill training. We tested the effects of aerobic exercise on irisin level, renal function, and EMT modulators in the kidney. We also treated angiotensin II-induced HK-2 cells with irisin and tested the changes in EMT levels. The data showed low and moderate aerobic exercise improved renal function and inhibited EMT through promoting irisin expression in SHR. However, high-intensity exercise training had no effect on renal injury and EMT in SHR but did significantly activate STAT3 phosphorylation in the kidney. These results clarify the mechanisms of exercise in improving hypertension-related renal injury and suggest that irisin might be a therapeutic target for patients with kidney injury.

An Intelligent Diagnostic Model for Melasma Based on Deep Learning and Multimode Image Input.

INTRODUCTION: The diagnosis of melasma is often based on the naked-eye judgment of physicians. However, this is a challenge for inexperienced physicians and non-professionals, and incorrect treatment might have serious consequences. Therefore, it is important to develop an accurate method for melasma diagnosis. The objective of this study is to develop and validate an intelligent diagnostic system based on deep learning for melasma images. METHODS: A total of 8010 images in the VISIA system, comprising 4005 images of patients with melasma and 4005 images of patients without melasma, were collected for training and testing. Inspired by four high-performance structures (i.e., DenseNet, ResNet, Swin Transformer, and MobileNet), the performances of deep learning models in melasma and non-melasma binary classifiers were evaluated. Furthermore, considering that there were five modes of images for each shot in VISIA, we fused these modes via multichannel image input in different combinations to explore whether multimode images could improve network performance. RESULTS: The proposed network based on DenseNet121 achieved the best performance with an accuracy of 93.68% and an area under the curve (AUC) of 97.86% on the test set for the melasma classifier. The results of the Gradient-weighted Class Activation Mapping showed that it was interpretable. In further experiments, for the five modes of the VISIA system, we found the best performing mode to be "BROWN SPOTS." Additionally, the combination of "NORMAL," "BROWN SPOTS," and "UV SPOTS" modes significantly improved the network performance, achieving the highest accuracy of 97.4% and AUC of 99.28%. CONCLUSIONS: In summary, deep learning is feasible for diagnosing melasma. The proposed network not only has excellent performance with clinical images of melasma, but can also acquire high accuracy by using multiple modes of images in VISIA.

Macrophages regulate vascular smooth muscle cell function during atherosclerosis progression through IL-1ß/STAT3 signaling.

Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis progression, but the functional changes in VSMCs and the associated cellular crosstalk during atherosclerosis progression remain unknown. Here we show that scRNA-seq analysis of proximal adjacent (PA) and atherosclerotic core (AC) regions of human carotid artery plaques identifies functional alterations in macrophage-like VSMCs, elucidating the main state differences between PA and AC VSMCs. And, IL-1ß mediates macrophage-macrophage-like VSMC crosstalk through regulating key transcription factors involved in macrophage-like VSMCs functional alterations during atherosclerosis progression. In vitro assays reveal VSMCs trans-differentiated into a macrophage-like phenotype and then functional alterations in response to macrophage-derived stimuli. IL-1ß promots the adhesion, inflammation, and apoptosis of macrophage-like VSMCs in a STAT3 dependent manner. The current findings provide interesting insight into the macrophages-macrophage-like VSMC crosstalk, which would drive functional alterations in the latter cell type through IL-1ß/STAT3 axis during atherosclerosis progression.

Association between frontal fibrosing Alopecia and Rosacea: Results from clinical observational studies and gene expression profiles.

Background: In recent years, frontal fibrosing alopecia (FFA), a type of scarring alopecia, has attracted increasing attention. Several studies have reported the frequent occurrence of rosacea in FFA; however, the association between FFA and rosacea and the underlying pathogenesis have not been thoroughly clarified. Thus, this study aimed to quantify these relationships and investigate their shared molecular mechanisms. Methods: We evaluated the association between FFA and rosacea by analyzing clinical data from nine observational studies. We then analyzed the gene expression profiles of FFA and rosacea. First, differential expression analysis and weighted gene co-expression network analysis were used to identify the common differentially expressed genes (DEGs). Later, we conducted a functional enrichment analysis and protein-protein interaction network and used seven algorithms to identify hub genes. Then, we performed a correlation analysis between the hub genes and the gene set variation analysis scores of common pathways in the gene set enrichment analysis (GSEA). The results were validated using different datasets. Finally, transcription factors were predicted and verified, and CIBERSORT and single-sample GSEA were used to estimate the infiltrating immune cells. Results: Patients with FFA had significantly higher odds for rosacea (pooled odds ratio [OR], 2.46; 95% confidence interval [CI], 1.78-3.40), and the pooled prevalence of rosacea in patients with FFA was 23% (95% CI, 14-23%). Furthermore, we identified 115 co-DEGs and 13 hub genes (CCR5, CCL19, CD2, CD38, CD83, CXCL8, CXCL9, CXCL10, CXCL11, CXCR4, IRF1, IRF8, and PTPRC). Seven pathways showed a high correlation with these hub genes. In addition, one TF, STAT1, was highly expressed in both diseases, and the results of the immune infiltration analysis indicated the importance of M1 macrophages and effector memory CD8+ T cells. Conclusion: This study contributes to the understanding of the relationship between FFA and rosacea, and based on the hub genes, we reveal the potential pathologies shared by the two diseases. This finding provides new insights of underlying molecular mechanisms and it may inspire future research on this comorbidity.

Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis.

Background: Hypoglycemia is a dangerous side effect of intensive glucose control in diabetes. Even though it leads to adverse cardiovascular events, the effects of hypoglycemia on vascular biology in diabetes have not been adequately studied. Methods: Aged Sprague-Dawley rats were fed a high-fat diet and given streptozotocin to induce type 2 diabetes mellitus (T2DM). Acute and recurrent hypoglycemia were then induced by glucose via insulin administration. Vascular function, oxidative stress, and pyroptosis levels in aortic tissue were assessed by physiological and biochemical methods. Results: Hypoglycemia was associated with a marked decrease in vascular function, elevated oxidative stress, and elevated pyroptosis levels in the thoracic aorta. The changes in oxidative stress and pyroptosis were greater in rats with recurrent hypoglycemia than in those with acute hypoglycemia. Conclusions: Hypoglycemia impaired vascular function in aged rats with T2DM by inducing pyroptosis. The extent of injury increased with the duration of blood glucose fluctuation.

Sex differences on outcomes following left atrial appendage occlusion in atrial fibrillation: A systematic review and meta-analysis.

There is a lack of sufficient data on sex-related differences in outcomes of nonvalvular atrial fibrillation (AF) patients following left atrial appendage occlusion (LAAO). We conducted a meta-analysis to investigate the procedural complications and long-term outcomes after LAAO in women versus men. We screened Medline, EMBASE, Cochrane Center Register of Controlled Trials, and Clinical Trials.gov. The inclusion criteria were studies targeting the sex-related differences in outcomes in nonvalvular AF patients treated by LAAO. Procedural endpoints of interest included success rate, pericardial complications, major bleeding, and vascular complications during hospitalization. Long-term outcomes included all-cause mortality and ischemic stroke during follow-up. Studies that merely considered sex in the subgroup analysis were not included. Six observational studies with a total of 64,035 patients were identified. The procedural success rates did not differ between sexes (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.89-1.09, p = 0.77), while women experienced more pericardial complications (OR: 1.78, 95% CI: 1.58-2.01, p < 0.00001), major bleedings (OR: 2.04, 95% CI: 1.75-2.39, p < 0.00001), and vascular complications (OR: 1.75, 95% CI: 1.41-2.17, p < 0.00001) than men. The sensitivity analysis performed by removing the largest study showed good stability. The long-term mortality and stroke rates did not differ between women and men in either the 1-year subgroup or the 2-year subgroup. In conclusion, despite comparable procedural success rates, women have a significantly higher incidence of pericardial complications, major bleeding, and vascular complications following LAAO. The long-term mortality and stroke rates do not differ between the sexes.

Blood Urea Nitrogen for Short-Term Prognosis in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction.

Purpose: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI). Our study aimed to evaluate the short-term prognostic value of admission blood urea nitrogen (BUN) in patients with CS complicating AMI. Materials and Methods: 218 consecutive patients with CS after AMI were enrolled. The primary endpoint was 30-day mortality. The association of admission BUN and 30-day mortality and major adverse cardiovascular event (MACE) was investigated by Cox regression. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) further examined the predictive value of BUN. Results: During a period of 30-day follow-up, 105 deaths occurred. Compared to survivors, nonsurvivors had significantly higher admission BUN (p < 0.001), creatinine (p < 0.001), BUN/creatinine (p = 0.03), and a lower glomerular filtration rate (p < 0.001). The area under the curve (AUC) of the 4 indices for predicting 30-day mortality was 0.781, 0.734, 0.588, and 0.773, respectively. When compared to traditional markers associated with CS, the AUC for predicting 30-day mortality of BUN, lactate, and left ventricular ejection fraction were 0.781, 0.776, and 0.701, respectively. The optimal cut-off value of BUN for predicting 30-day mortality was 8.95 mmol/L with Youden-Index analysis. Multivariate Cox analysis indicated BUN >8.95 mmol/L was an important independent predictor for 30-day mortality (HR 2.08, 95%CI 1.28-3.36, p = 0.003) and 30-day MACE (HR 1.85, 95%CI 1.29-2.66, p = 0.001). IDI (0.053, p = 0.005) and NRI (0.135, p = 0.010) showed an improvement in the accuracy for mortality prediction of the new model when BUN was included compared with the standard model of predictors in previous scores. Conclusion: An admission BUN >8.95 mmol/L was robustly associated with increased short-term mortality and MACE in patients with CS after AMI. The prognostic value of BUN was superior to other renal markers and comparable to traditional markers. This easily accessible index might be promising for early risk stratification in CS patients following AMI.

Incidence, Clinical Characteristics and Short-Term Prognosis in Patients With Cardiogenic Shock and Various Left Ventricular Ejection Fractions After Acute Myocardial Infarction.

The 2016 European Society of Cardiology Guidelines introduced a new term, mid-range left ventricular ejection fraction (mrEF) heart failure, however, the clinical characteristics and short-term outcomes in cardiogenic shock patients with mrEF after acute myocardial infarction remain unclear. This retrospective study analyzed the baseline characteristics, management, and outcomes according to the left ventricular ejection fraction (LVEF), reduced LVEF (rEF) ≤40%, mrEF 41% to 49%, and preserved LVEF (pEF) ≥50% in patients with acute myocardial infarction complicated by cardiogenic shock. The primary end point was 30-day all-cause mortality and the secondary end point was the composite events of major adverse cardiovascular events (MACEs). In 218 patients, 71 (32.6%) were patients with mrEF. Compared with those with pEF, patients with mrEF had some similar clinical characteristics to that of rEF. The 30-day all-cause mortality in patients with rEF, mrEF, and pEF were 72.7%, 56.3%, and 32.0%, respectively (p = 0.001). The 30-day MACE were 90.9%, 69.0%, and 60.2%, respectively (p = 0.001). After multivariable adjustment, patients with mrEF and rEF had comparable 30-day all-cause mortality (hazard ratio [HR] = 0.81, 95% confidence interval [CI] 0.50 to 1.33, p = 0.404), and pEF was associated with decreased risk of 30-day all-cause mortality compared with rEF (HR = 0.41, 95% CI 0.24 to 0.71, p = 0.001). In contrast, the risk of 30-day MACE in mrEF and pEF were lower than that of rEF (HR = 0.62, 95% CI 0.40 to 0.96, p = 0.031 and HR = 0.53, 95% CI 0.34 to 0.80, p = 0.003, respectively). In conclusion, 1/3 of patients with acute myocardial infarction complicated by cardiogenic shock were mrEF. The clinical characteristics and short-term mortality in patients with mrEF were inclined to that of rEF and the occurrence of early left ventricular systolic dysfunction is of prognostic significance.

Leukocyte and its Subtypes as Predictors of Short-Term Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI. METHODS: Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis. RESULTS: Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 × 109/L) (HR 1.815; 95%CI 1.134, 2.903; P = 0.013), low eosinophil (<0.3%) (HR 2.562; 95%CI 1.412, 4.648; P = 0.002) and low basophil (≤0.1%) (HR 1.694; 95%CI 1.106, 2.592; P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 × 109/L) (HR 1.894; 95%CI 1.285, 2.791; P = 0.001), low eosinophil (<0.3%) (HR 1.729; 95%CI 1.119, 2.670; P = 0.014) and low basophil (≤0.1%) (HR 1.560; 95%CI 1.101, 2.210; P = 0.012) were independently associated with increased risk of 30-day MACE. CONCLUSIONS: Leukocyte and its subtypes changed significantly in patients with CS complicating AMI. In addition to leukocyte, eosinophil and basophil also served as independent prognostic factors for 30-day outcomes. Moreover, as the composite of leukocyte and its subtypes increased the predictive power, thus leukocyte and its subtypes, especially eosinophil and basophil should be taken into consideration for the current risk stratification model.

The Association of Thyroid Hormones With Cardiogenic Shock and Prognosis in Patients with ST Segment Elevation Myocardial Infarction (STEMI) Treated with Primary PCI.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of the death in patients with ST elevation myocardial infarction (STEMI). Thyroid dysfunction is related to prognosis of patients with myocardial infarction. Hence, the aim of this study is to explore the relationship between thyroid hormones (free triiodothyronine [FT3] and free thyroxine [FT4]) and CS. METHODS: A total of 1270 patients with STEMI treated with percutaneous coronary intervention (PCI) were consecutively enrolled in our study. Patients were classified into two groups according to with or without CS during hospitalization. Stepwise multivariate logistic analysis was conducted to investigate the association of thyroid hormones and CS. Restricted cubic spline method was employed to further explore the relationship between CS and thyroid hormones. RESULTS: Patients who developed CS (n=103) had lower FT3 and higher FT4 upon admission. The stepwise logistic analysis showed both FT3 (P=0.038) and FT4 (P=0.024) were independently related to CS. Restricted cubic splines indicated that lower FT3 (<2.25 pg/ml) or higher FT4 (>1.25 ng/dl) were correlated with higher prevalence of CS. Over 2.5 years' follow-up, patients (n=294) with low FT3 (<2.85 pg/ml) and high FT4 (>=0.88 ng/dl) had the highest all-cause mortality (18.2%), whereas patients (n=293) with high FT3 and low FT4 had the lowest all-cause mortality (3.8%) (P for trend <0.0001). CONCLUSIONS: Both FT3 and FT4 were independently associated with in-hospital CS development in patients with STEMI treated with PCI. Patients with lower range of FT3 and upper range of FT4 had the worst outcomes in long-term follow-up.