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Background: Insulin resistance (IR) is closely related to the development of cardiovascular diseases. Triglyceride-glucose-body mass index (TyG-BMI) has been proven to be a reliable surrogate of IR, but the relationship between TyG-BMI and acute myocardial infarction (AMI) is unknown. The present study aims to determine the effects of TyG-BMI on the clinical prognosis of critically ill patients with AMI. Methods: The data of AMI patients were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were divided into four groups according to the TyG-BMI quartile. Outcomes were defined as 30-, 90-, 180-, and 365-day all-cause mortality. Kaplan-Meier (K-M) curve was used to compare survival rate between groups. Meanwhile, Cox regression analysis and restricted cubic splines (RCS) were used to explore the relationship between TyG-BMI index and outcome events. Results: A total of 1,188 critically ill patients with AMI were included in this study. They were divided into four groups according to TyG-BMI quartiles, there were significant differences in 90-, 180-, and 365-day all-cause mortality while there was no difference in 30-day all-cause mortality. Interestingly, with the increase of TyG-BMI, the 90-, 180-, and 365-day survival rate increased first and then gradually decreased, but the survival rate after decreasing was still higher than that in the group with the lowest TyG-BMI. U-shaped relationships between TyG-BMI index and 90-, 180-, and 365-day all-cause mortality were identified using RCS curve and the inflection point was 311.1, 316.5, and 320.1, respectively, whereas the TyG-BMI index was not non-linearly associated with 30-day all-cause mortality. The results of Cox proportional hazard regression analysis are consistent with those of RCS analysis. Conclusion: U-shaped relationships are existed between the TyG-BMI index and 90-, 180-, and 365-day all-cause mortality in critically ill patients with AMI, but not 30-day all-cause mortality. The TyG-BMI index can be used as an effective index for early prevention of critically ill patients with AMI.
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Background: Inflammation is related to cardiovascular disease. Among the many inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) were considered as novel predictors for atherosclerosis outcomes. We aimed to investigate the impact of these inflammatory markers on the prognosis of patients with atrial fibrillation (AF). Methods: We obtained data on AF patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. These patients were classified into two groups based on their survival status within 30 days. Then, they were divided into three groups based on the tertile of baseline NLR, PLR, and SII, respectively. We comprehensively explored the relationship between those inflammatory indicators and all-cause mortality in patients with AF by Kaplan-Meier analysis, multivariate Cox regression analysis, receiver operating characteristic (ROC) analyses, restricted cubic spline regression (RCS), and subgroup analysis. Results: A total of 4562 patients with AF were included. Statistically significant differences were found between survivor and non-survivor groups for NLR, PLR and SII. Patients in the high tertile of the NLR had a higher mortality rate than those in the low and intermediate tertiles, as did patients in the PLR and the SII. NLR, PLR and SII were independently associated with increased risk of all-cause mortality. RCS showed that the 30-day and 365-day risk of death were linearly associated with increases in NLR, PLR, and SII, respectively. Conclusion: NLR, PLR, and SII have the potential to be used as indicators for stratifying the risk of mortality in critically ill patients with AF.
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Objective: To examine the impact of moderate alcohol consumption on the progression of chronic kidney disease (CKD) in individuals diagnosed with non-alcoholic fatty liver disease (NAFLD), as NAFLD has been identified as an autonomous risk factor for CKD and previous research has demonstrated a reduction in overall mortality in NAFLD patients who consume alcohol in moderation.Methods: This study included participants from ten consecutive rounds of the National Health and Nutrition Examination Survey (NHANES:1998-2018). Multivariate logistic regression models were employed to assess the impact of moderate alcohol consumption on chronic kidney disease (CKD) in both male and female populations. Subgroup analysis was conducted by categorizing patients with non-alcoholic fatty liver disease (NAFLD) based on the Fibrosis-4 (FIB-4) index.Results: 17040 participants were eligible to be included in the study. The logistic regression analysis model showed that moderate alcohol consumption was a protective factor for CKD in male NAFLD patients, with an unadjusted OR: 0.37 (0.22,0.65), and p < 0.001. After further adjustment, the association persisted. However, the association was not significant in female patients with NAFLD. Among men with low risk of liver fibrosis group, moderate alcohol consumption remained a protective factor for CKD (OR = 0.32, 95% CI 0.12-0.84, p = 0.02), but the association was not significant in the high risk of liver fibrosis group. In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group.Conclusion: Moderate alcohol consumption is associated with a lower prevalence of CKD in men with NAFLD.
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Stéatose hépatique non alcoolique , Insuffisance rénale chronique , Humains , Mâle , Femelle , Stéatose hépatique non alcoolique/complications , Stéatose hépatique non alcoolique/épidémiologie , Enquêtes nutritionnelles , Insuffisance rénale chronique/épidémiologie , Insuffisance rénale chronique/étiologie , Consommation d'alcool/effets indésirables , Consommation d'alcool/épidémiologie , Cirrhose du foie/complicationsRÉSUMÉ
OBJECTIVE: Current guidelines are debated when it comes to starting anticoagulant therapy in patients with non-valvular atrial fibrillation (NVAF) and low CHA2DS2-VASc scores (1-2 in women and 0-1 in men). However, these individuals still have a high likelihood of developing left atrial thrombus/spontaneous echo contrast (LAT/SEC) and experiencing subsequent thromboembolism. Recent research has demonstrated that lipoprotein(a) [Lp(a)] may increase the risk of thrombosis, but the relationship between Lp(a) and LAT/SEC in NVAF patients is not clearly established. Therefore, this study sought to evaluate the predictive ability of Lp(a) for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. METHODS: NVAF patients with available transesophageal echocardiography (TEE) data were evaluated. Based on the TEE results, the subjects were classified into non-LAT/SEC and LAT/SEC groups. The risk factors for LAT/SEC were examined using binary logistic regression analyses and were validated by using 1:1 propensity score matching (PSM). Subsequently, novel predictive models for LAT/SEC were developed by integrating the CHA2DS2-VASc score with the identified factors, and the accuracy of these models was tested using receiver operating characteristic (ROC) analysis. RESULTS: In total, 481 NVAF patients were enrolled. The LAT/SEC group displayed higher Lp(a) concentrations. It was found that enlarged left atrial diameter (LAD), high concentrations of Lp(a), and a history of coronary heart disease (CHD) were independent predictors of LAT/SEC. Lp(a) and LAD still had predictive values for LAT/SEC after adjusting for PSM. In both the highest quartile groups of Lp(a) (>266 mg/L) and LAD (>39.5 mm), the occurrence of LAT/SEC was higher than that in the corresponding lowest quartile. By incorporating Lp(a) and the LAD, the predictive value of the CHA2DS2-VASc score for LAT/SEC was significantly improved. CONCLUSION: Elevated Lp(a) and enlarged LAD were independent risk factors for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. The prediction accuracy of the CHA2DS2-VASc score for LAT/SEC was significantly improved by the addition of Lp(a) and LAD. When evaluating the stroke risk in patients with NVAF, Lp(a) and LAD should be taken into account together with the CHA2DS2-VASc score. TRIAL REGISTRATION: Retrospectively registered.
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Fibrillation auriculaire , Lipoprotéine (a) , Thrombose , Femelle , Humains , Mâle , Fibrillation auriculaire/complications , Fibrillation auriculaire/imagerie diagnostique , Études transversales , Score de propension , Thrombose/imagerie diagnostique , Thrombose/étiologieRÉSUMÉ
It has been demonstrated that lactate/albumin (L/A) ratio is substantially relevant to the prognosis of sepsis, septic shock, and heart failure. However, there is still debate regarding the connection between the L/A ratio and severe acute myocardial infarction (AMI). The aim of this study is to determine the prognostic role of L/A ratio in patients with severe AMI. Our retrospective study extracted data from the Medical Information Mart for Intensive Care III (MIMIC-III) database, included 1,134 patients diagnosed with AMI. Based on the tertiles of L/A ratio, the patients were divided into three groups: Tertile1 (T1) group (L/A ratio<0.4063, n=379), Tertile2 (T2) group (0.4063≤L/A ratio≤0.6667, n =379), and Tertile3 (T3) group (L/A ratio>0.6667, n =376). Uni- and multivariate COX regression model were used to analyze the relationship between L/A ratio and 14-day, 28-day and 90-day all-cause mortality. Meanwhile, the restricted cubic spline (RCS) model was used to evaluate the effect of L/A ratio as a continuous variable. Higher mortality was observed in AMI patients with higher L/A ratio. Multivariate Cox proportional risk model validated the independent association of L/A ratio with 14-day all-cause mortality [hazard ratio (HR) 1.813, 95% confidence interval (CI) 1.041-3.156 (T3 vs T1 group)], 28-day all-cause mortality [HR 1.725, 95% CI 1.035-2.874 (T2 vs T1 group), HR 1.991, 95% CI 1.214-3.266 (T3 vs T1 group)], as well as 90-day all-cause mortality [HR 1.934, 95% CI 1.176-3.183 (T2 vs T1 group), HR 2.307, 95% CI 1.426-3.733 (T3 vs T1 group)]. There was a consistent trend in subgroup analysis. The Kaplan-Meier (K-M) survival curves indicated that patients with L/A ratio>0.6667 had the highest mortality. Even after adjusting the confounding factors, RCS curves revealed a nearly linearity between L/A ratio and 14-day, 28-day and 90-day all-cause mortality. Meanwhile, the areas under the receiver operating characteristic (ROC) curve (AUC) of 14-day, 28-day and 90-day all-cause mortality were 0.730, 0.725 and 0.730, respectively. L/A ratio was significantly associated with 14-day, 28-day and 90-day all-cause mortality in critical patients with AMI. Higher L/A ratio will be considered an independent risk factor for higher mortality in AMI patients.
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Acide lactique , Infarctus du myocarde , Humains , Études rétrospectives , Albumines , Soins de réanimationRÉSUMÉ
Low heart rate is a risk factor of mortality in many cardiovascular diseases. However, the relationship of minimum heart rate (MHR) with outcomes after cardiac surgery is still unclear, and the association between optimum MHR and risk of mortality in patients receiving cardiac surgery remains unknown. In this retrospective study using the Multi-parameter Intelligent Monitoring in Intensive Care (MIMIC-III) database, 8243 adult patients who underwent cardiac surgery were included. The association between MHR and the 30-day, 90-day, 180-day, and 1-year mortality of patients undergoing cardiac surgery was analyzed using multivariate Cox proportional hazard analysis. As a continuous variable, MHR was evaluated using restricted cubic regression splines, and appropriate cut-off points were determined. Kaplan-Meier curve was used to further explore the relationship between MHR and prognosis. Subgroup analyses were performed based on age, sex, hypertension, diabetes, and ethnicity. The rates of the 30-day, 90-day, 180-day, and 1-year mortalities of patients in the low MHR group were higher than those in the high MHR group (4.1% vs. 2.9%, P < 0.05; 6.8% vs. 5.3%, P < 0.05; 8.9% vs. 7.0%, P < 0.05, and 10.9% vs. 8.8%, P < 0.05, respectively). Low MHR significantly correlated with the 30-day, 90-day, 180-day, and 1-year mortality after adjusting for confounders. A U-shaped relationship was observed between the 30-day, 90-day, 180-day, and 1-year mortality and MHR, and the mortality was lowest when the MHR was 69 bpm. Kaplan-Meier curve analysis also indicated that low MHR had poor prognosis in patients undergoing cardiac surgery. According to subgroup analyses, the effect of low MHR on post-cardiac surgery survival was restricted to patients who were < 75 years old, male, without hypertension and diabetes, and of White ethnicity. MHR (69 bpm) was associated with better 30-day, 90-day, 180-day, and 1-year survival in patients after cardiac surgery. Therefore, effective HR control strategies are required in this high-risk population.
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Procédures de chirurgie cardiaque , Rythme cardiaque , Complications postopératoires , Adulte , Sujet âgé , Humains , Mâle , Procédures de chirurgie cardiaque/effets indésirables , Soins de réanimation , Diabète , Hypertension artérielle , Pronostic , Études rétrospectives , Complications postopératoires/mortalitéRÉSUMÉ
BACKGROUND: The significantly prognostic value of fibrinogen-to-albumin ratio (FAR) has been proved in patients with coronary artery disease and different oncologic disorders. This study aimed to investigate the predictive value of FAR for left ventricular systolic dysfunction (LVSD) in acute coronary syndromes (ACS) patients. METHODS: A total of 650 ACS patients after percutaneous coronary intervention (PCI) were eventually enrolled in the analysis. Participants were classified into three groups according to baseline FAR levels (T1: FAR < 73.00; T2: 73.00 ≤ FAR < 91.00; T3: FAR ≥ 91.00). The association between FAR and LVSD was assessed by binary logistic regression analysis. A nomogram to predict the risk of LVSD was constructed based on the output indices from multivariate regression analyses. RESULTS: Patients with LVSD showed significantly higher FAR, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without. FAR was an independent predictor of left ventricular dysfunction from the multivariate analyses (OR, 1.038; 95%CI, 1.020-1.057; P < 0.001). The area under receiver operating characteristic curve (AUC) of FAR predicting the occurrence of LVSD was 0.735. Meanwhile, FAR was the most powerful predictor than MLR, NLR, and PLR. Nomogram with the AUC reaching 0.906 showed a robust discrimination. CONCLUSIONS: Admission FAR is independently and significantly associated with LVSD in patients with ACS undergoing PCI.
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Syndrome coronarien aigu , Intervention coronarienne percutanée , Dysfonction ventriculaire gauche , Humains , Syndrome coronarien aigu/complications , Études transversales , Albumines , Fibrinogène , Études rétrospectivesRÉSUMÉ
BACKGROUND: Coronary artery disease (CAD) tends to progress more rapidly in the type 2 diabetes mellitus (T2DM) population and may be associated with dyslipidemia. This study explored the relationship of the atherogenic index of plasma (AIP) to coronary artery lesions in the T2DM population of different sexes. METHODS: The research included 737 individuals who underwent coronary angiography from 2018 to 2019. The included clinical data and coronary angiographic findings were analyzed in the study. RESULTS: Among the included male patients, those with coronary artery disease had a higher adjusted AIP (aAIP). In correlation analysis, the Gensini score was positively and linearly correlated with the aAIP in male T2DM patients. An aAIP cutoff value of 1.17 was determined from the receiver operating characteristic (ROC) curve of aAIP versus CAD risk in the study population. After dividing the aAIP into two groups by the cutoff value of aAIP, the group with the lower value was used as the control for logistic regression analysis. The results showed that the risk of CAD and multivessel lesions was higher when the aAIP was higher in men with T2DM, and this positive association was not affected by HbA1c, age, or the presence of glucose-lowering therapy. The ROC curve suggested that the aAIP can predict CAD risk in male T2DM patients. However, no relationship was found in the included female patients. CONCLUSION: In male T2DM patients, AIP may serve as a reliable marker for coronary artery lesions.
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Athérosclérose , Maladie des artères coronaires , Diabète de type 2 , Humains , Mâle , Femelle , Études transversales , Facteurs de risque , Caractères sexuels , Coronarographie/méthodesRÉSUMÉ
Background: Base excess (BE) represents an increase or decrease of alkali reserves in plasma to diagnose acid-base disorders, independent of respiratory factors. Current findings about the prognostic value of BE on mortality of patients with acute myocardial infarction (AMI) are still unclear. The purpose of this study was to explore the prognostic significance of BE for short-term all-cause mortality in patients with AMI. Methods: A total of 2,465 patients diagnosed with AMI in the intensive care unit from the Medical Information Mart for Intensive Care III (MIMIC-III) database were included in our study, and we explored the association of BE with 28-day and 90-day all-cause mortality using Cox regression analysis. We also used restricted cubic splines (RCS) to evaluate the relationship between BE and hazard ratio (HR). The primary outcomes were 28-day and 90-day all-cause mortality. Results: When stratified according to quantiles, low BE levels at admission were strongly associated with higher 28-day and 90-day all-cause mortality. Multivariable Cox proportional hazard models revealed that low BE was an independent risk factor of 28-day all-cause mortality [HR 4.158, 95% CI 3.203-5.398 (low vs. normal BE) and HR 1.354, 95% CI 0.896-2.049 (high vs. normal BE)] and 90-day all-cause mortality [HR 4.078, 95% CI 3.160-5.263 (low vs. normal BE) and HR 1.369, 95% CI 0.917-2.045 (high vs. normal BE)], even after adjustment for significant prognostic covariates. The results were also consistent in subgroup analysis. RCS revealed an "L-type" relationship between BE and 28-day and 90-day all-cause mortality, as well as adjusting for confounding variables. Meanwhile, Kaplan-Meier survival curves were stratified by combining BE with carbon dioxide partial pressure (PaCO2), and patients had the highest mortality in the group which had low BE (< 3.5 mEq/L) and high PaCO2 (> 45 mmHg) compared with other groups. Conclusion: Our study revealed that low BE was significantly associated with 28-day and 90-day mortality in patients with AMI and indicated the value of stratifying the mortality risk of patients with AMI by BE.
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OBJECTIVE: Although the levels of plasma fibrinogen and albumin have been proven to be in relation to coronary heart disease (CHD), the association between fibrinogen-to-albumin ratio (FAR) and acute coronary syndrome (ACS) has not been adequately investigated. The aim of this study is to investigate the relationship between FAR and the presence and severity of CHD in patients with ACS. METHODS AND RESULTS: A total of 1575 individuals who received coronary angiography (CAG) were enrolled. Patients were divided into the ACS group and the control group. The severity of ACS was determined by Gensini score, number of diseased coronary artery and the presence of myocardial infarction (MI). Data showed that the level of FAR in ACS group was higher than in the control group (81.20 ± 35.45 vs. 72.89 ± 20.24, P < 0.001). The results from subgroup analysis indicated that the values of FAR in the high Gensini score group, MI group and multiple-vessel stenosis group were higher than the matched subgroups. After adjustment for confounders, FAR was still independently related to the presence and severity of ACS (MI OR 2.097, 95%CI 1.430-3.076; High GS: OR 2.335, 95%CI 1.567-3.479; multiple-vessel disease: OR 2.088, 95%CI 1.439-3.030; P < 0.05). CONCLUSION: The levels of FAR are independently associated with the presence and the severity of coronary artery disease in patients with ACS. Furthermore, FAR, as a more convenient and rapid biological indicator, may provide a new idea for predicting the presence and severity of ACS.
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Syndrome coronarien aigu/sang , Maladie des artères coronaires/sang , Fibrinogène/analyse , Infarctus du myocarde/sang , Sérum-albumine humaine/analyse , Syndrome coronarien aigu/imagerie diagnostique , Sujet âgé , Marqueurs biologiques/sang , Coronarographie , Maladie des artères coronaires/imagerie diagnostique , Études transversales , Femelle , Humains , Mâle , Adulte d'âge moyen , Infarctus du myocarde/imagerie diagnostique , Acuité des besoins du patient , Valeur prédictive des tests , Appréciation des risques , Facteurs de risqueRÉSUMÉ
Background Pathophysiologic mechanisms underlying cardiac structural and functional changes in obesity are complex and linked to adipocytokines released from pericardial adipose tissue (PAT) and cardiomyocyte apoptosis. Although leptin is involved in various pathological conditions, its role in paracrine action of pericardial adipose tissue on myocardial apoptosis remains unknown. This study was designed to investigate the role of PAT-derived leptin on myocardial apoptosis in high-fat diet-induced obese rats. Methods and Results Hearts were isolated from lean or high-fat diet-induced obese Wistar rats for myocardial remodeling studies. Obese rats had abnormal myocardial structure, diastolic dysfunction, greatly elevated cardiac apoptosis, enhanced cardiac fibrosis, and increased oxidative stress level. ELISA detected significantly higher than circulating leptin level in PAT of obese, but not lean, rats. Western blot and immunohistochemical analyses demonstrated increased leptin receptor density in obese hearts. H9c2 cardiomyoblasts, after being exposed to PAT-conditioned medium of obese rats, exhibited pronounced reactive oxygen species-mediated apoptosis, which was partially reversed by leptin antagonist. Moreover, leptin derived from PAT of obese rats inhibited Na+/K+-ATPase activity of H9c2 cells through stimulating reactive oxygen species, thereby activating calcium-dependent apoptosis. Pretreatment with specific inhibitors revealed that Janus kinase 2/signal transducer and activator of transcription 3 and phosphoinositide 3-kinase/protein kinase B signaling pathways were involved in leptin-induced myocardial apoptosis. Conclusions PAT-derived leptin induces myocardial apoptosis in high-fat diet-induced obese rats via activating Janus kinase 2/signal transducer and activator of transcription 3/reactive oxygen species signaling pathway and inhibiting its downstream Na+/K+-ATPase activity.
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Apoptose , Leptine , Myocytes cardiaques , Transduction du signal , Tissu adipeux , Animaux , Alimentation riche en graisse , Kinase Janus-2 , Myocytes cardiaques/cytologie , Obésité , Phosphatidylinositol 3-kinases , Rats , Rat Wistar , Espèces réactives de l'oxygène , Facteur de transcription STAT-3 , Sodium-Potassium-Exchanging ATPaseRÉSUMÉ
BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital heart defect usually accompanied with different hemodynamic abnormalities. Due to the rarity of QAV, treatment and prognosis of QAV patients with aortic regurgitation still remain challenging. We here present the first case of a patient with severe QAV regurgitation who underwent successful treatment and performed favorable prognosis with transapical aortic valve implantation (TAVI) using J-Valve system. CASE PRESENTATION: A 62-year-old man experienced intermittent palpitation, shortness of breath and chest pain. Echocardiography revealed congenital QAV with massive aortic regurgitation and mild aortic stenosis, left ventricular enlargement. Aortic valve replacement was successfully performed with TAVI using J-Valve system. The postoperation and follow-up was uneventful. CONCLUSION: TAVI using J-Valve system has emerged as a new high success rate method for treatment of patients with simple non-calcified aortic valve insufficiency.
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Insuffisance aortique , Valve aortique quadricuspide , Valve aortique/imagerie diagnostique , Valve aortique/chirurgie , Insuffisance aortique/imagerie diagnostique , Insuffisance aortique/chirurgie , Cathéters , Humains , Mâle , Adulte d'âge moyen , Débit systolique , Fonction ventriculaire gaucheRÉSUMÉ
BACKGROUND: Intra-aortic foreign body (IAFB) is uncommon, which is usually caused by a rupture of the catheter or guidewire. IAFB can cause catastrophic complications, including arrhythmia, embolization of guidewire fragments, intravascular clipping of the guidewire and vascular perforation. However, there are still no guidelines on removal and management of IAFB. Here, we present a rare case of fractured cerebral angiographic guidewires in the aorta that resulted in multiple cerebral infarctions. CASE PRESENTATION: A 50-year-old man experienced new cerebral infarction after cerebral angiography. Computed tomography and echocardiography demonstrated foreign bodies in his ascending aorta and aortic arch. Open surgery was successfully performed to retrieve the guidewires. The postoperation and follow-up was uneventful. CONCLUSION: It is very important for interventional radiologists to check the catheter and guidewire after operation and perform ultrasound or radiograph to prevent IAFB. Additionally, the effective management of IAFB requires the early detection and the selection of appropriate treatment options, as well as long-time follow up.
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Aorte , Angiographie cérébrale/instrumentation , Infarctus cérébral/étiologie , Corps étrangers/chirurgie , Aorte/imagerie diagnostique , Infarctus cérébral/imagerie diagnostique , Échocardiographie , Corps étrangers/complications , Corps étrangers/imagerie diagnostique , Humains , Mâle , Adulte d'âge moyen , Radiographie , Tomodensitométrie , Lésions du système vasculaireRÉSUMÉ
Properties of mutant human ether-à-go-go-related gene (hERG) channels can be modified by some antibiotics. However, the pharmacological effects of posaconazole on cardiomyocyte hERG channels remain unclear. Whole-cell patch clamping, western blotting and laser confocal scanning microscopy were used to evaluate the effects of posaconazole on wild-type (WT)-, A561V- and L539 fs/47-hERG channels expressed in human embryonic kidney (HEK) 293 cells. In electrophysiological experiments, HEK 293 cells were transiently co-transfected with equal amounts of WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG plasmids to mimic a heterozygous genotype. Posaconazole (30 µM) increased tail currents in cells expressing WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG by 82.65%, 147.72% and 134.73%, respectively, compared to controls. Posaconazole increased hERG protein expression in cells expressing WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG compared to controls condition as well as their trafficking to the cell membrane. To our knowledge, this is the first study to show that antifungal agent posaconazole rescues the mutant A561 V-hERG and L539 fs/47-hERG channels by altering the gating kinetics, enhancing the expression and trafficking of hERG channels. The results demonstrate that posaconazole could be a promising candidate for the prevention and treatment of long QT syndrome and other arrhythmia-related diseases.
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Canaux potassiques éther-à-go-go , Syndrome du QT long , Triazoles , Phénomènes électrophysiologiques , Cellules HEK293 , Hétérozygote , Humains , Techniques de patch-clampRÉSUMÉ
BACKGROUND: Prolonged QT intervals have been observed in pregnant women, which predispose them to a higher risk of potentially lethal ventricular arrhythmias. This study was designed to evaluate the prevalence of QTc prolongation in Chinese hospitalized parturient women with single and twin pregnancies, and to explore potential risk factors associated with QTc prolongation. METHODS: This retrospective study included 1,218 patients from a large Chinese population between January 2014 and October 2020. Data from parturient women with single and twin pregnancies without pre-pregnancy cardiac diseases were collected. QTc was corrected by the Fridericia formula [QTc = QT/RR(1/3)], and QTc ≥ 460 ms for females was defined as prolonged QTc, QTc ≥ 500 ms was defined as severely prolonged QTc. The prevalence and common risk factors of QTc prolongation during pregnancy were analyzed in this cohort. Uni- and multivariable logistic regression analysis were performed to identify clinical parameters associated with QTc prolongation in this population. RESULTS: The prevalence of QTc prolongation was 48.19% among this population, 10.56% in single pregnancy, 89.44% in twin pregnancies. The prevalence of severely prolonged QTc was 23.48% among the total cohort, 0.49% in single pregnancy, and 46.47% in twin pregnancies. The mean QTc interval was significantly longer in twin pregnancies than in single pregnancy (498.65 ± 38.24 vs. 424.96 ± 27.67 ms, P < 0.001). Systolic blood pressure, diastolic blood pressure, total cholesterol, serum uric acid, gestational hypertension and twin pregnancies were associated with QTc prolongation in parturient women. CONCLUSION: This is the first study to assess the prevalence and risk factors of QTc prolongation between single and twin pregnancies. QTc prolongation is more prevalent, and QTc intervals are significantly longer in twin pregnancies as compared to single pregnancy.
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OBJECTIVE: To investigate the relationship of 1-h postload plasma glucose during the oral glucose tolerance test with the severity of coronary artery lesions and risk of 1-year re-admission in coronary heart disease patients with normal glucose tolerance. METHODS: A total of 266 consecutive coronary heart disease patients who underwent coronary angiography and had normal glucose tolerance confirmed by oral glucose tolerance test during hospitalization were prospectively enrolled and followed in two groups according to the 1-h postload plasma glucose cut-off point (1-h postload plasma glucose <155 mg/dL, n = 149 and 1-h postload plasma glucose ⩾155 mg/dL, n = 117). Angiographic severity was assessed by number of diseased vessels, lesion morphology and Gensini score. The risk of 1-year re-admission with adverse cardiovascular events after discharge was analysed. RESULTS: Subjects with a 1-h postload plasma glucose ⩾155 mg/dL had higher incidence of multivessel disease and complex lesions, Gensini score and risk of 1-year re-admission than subjects with a 1-h postload plasma glucose <155 mg/dL (all p < 0.05). In the stepwise multivariate regression analysis, 1-h postload plasma glucose was the major determinant of the Gensini score. Subgroup analyses by sex showed that men with a 1-h postload plasma glucose ⩾155 mg/dL had higher incidence of complex lesions and risk of 1-year re-admission than men with a 1-h postload plasma glucose <155 mg/dL (all p < 0.05). CONCLUSION: Coronary heart disease patients with normal glucose tolerance and elevated 1-h postload plasma glucose levels had a greater severity of coronary artery lesions and an increased risk of re-admission with adverse cardiovascular events, particularly in men.