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Aim: This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites. Methods: We systematically searched the PubMed, Embase, and Cochrane databases for trials investigating ICI-based therapies published between their inception and August 2023. Results: In total, 147 studies involving 45,855 patients met the inclusion criteria. Among them, patients treated with ICIs reported 39.8% and 14.9% of all-grade and grade ≥3 immune-related adverse events (irAEs), respectively. The most common all-grade irAEs were dermatological and gastrointestinal issues, diarrhea, and pruritus, whereas patients who received ICIs showed most common grade ≥3 irAEs, including gastrointestinal events, diarrhea, increased aspartate aminotransferase and alanine transaminase levels, and hepatic and dermatological events. The overall trAE incidence in patients treated with ICIs was 83.2% for all-grade trAEs and 38.2% for grade ≥3 trAEs. TrAE incidence was highest for patients treated with cytotoxic T lymphocyte antigen-4 inhibitors for all-grade and grade ≥3 trAEs, with incidences of 86.4% and 39.2%, respectively. ICIs combined with targeted therapy showed the highest all-grade and grade ≥3 trAEs, with incidences of 96.3% and 59.4%, respectively. The most common all-grade trAEs were anemia, decrease in white blood cell count, decrease in neutrophil count, nausea, fatigue, diarrhea, and alopecia; patients who received ICIs presented relatively high incidences of grade ≥3 trAEs. Conclusion: This study provided comprehensive data regarding irAEs and trAEs in patients receiving ICIs. These results should be applied in clinical practice to provide an essential reference for safety profiles of ICIs. Systematic review registration: INPLASY platform, identifier INPLASY202380119.
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AIMS: The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an alternative to cardiac magnetic resonance (CMR) myocardial injury makers for risk stratification and prediction of left ventricular function (LVF) recovery among patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This multicentre observational study enrolled 328 STEMI patients (88.4% men, 57.3 ± 10.6 years of age) undergoing CMR examination 1 week post-reperfusion therapy. Patients with baseline left ventricular ejection fraction (LVEF) < 50% underwent a follow-up CMR 6 months later, categorized into baseline normal LVF (ejection fraction [EF] ≥ 50% at baseline, n = 155); recovered LVF (EF < 50% at baseline and ≥50% after 6 months, n = 69); and reduced LVF (EF < 50% at baseline and after 6 months, n = 104). The median follow-up was 4 (3-4) years for all patients, with 61 patients experiencing major adverse cardiovascular event (MACEs). Patients with reduced LVF had a higher risk of MACEs than those with baseline normal LVF (P = 0.01), while the recovered LVF group had no significant difference (P > 0.05). A Selvester score >10 doubled the risk of MACEs in patients with systolic dysfunction (1.91 [1.02 to 3.58], P = 0.04). Additionally, Selvester score, baseline LVEF, transmural infarction, and peak CK-MB were independent predictors of recovered LVF, with Selvester score providing incremental predictive value to peak CK-MB in predicting recovered LVF (∆AUC = 0.07, P < 0.05). CONCLUSIONS: The Selvester score improves risk stratification among STEMI patients beyond LVEF and provide independent and incremental information to clinical parameters in predicting recovered LVF.
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OBJECTIVE: To investigate the predictive value of radiomics features based on cardiac magnetic resonance (CMR) cine images for left ventricular adverse remodeling (LVAR) after acute ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: We conducted a retrospective, single-center, cohort study involving 244 patients (random-split into 170 and 74 for training and testing, respectively) having an acute STEMI (88.5% males, 57.0 ± 10.3 years of age) who underwent CMR examination at one week and six months after percutaneous coronary intervention. LVAR was defined as a 20% increase in left ventricular end-diastolic volume 6 months after acute STEMI. Radiomics features were extracted from the one-week CMR cine images using the least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the selected features was evaluated using receiver operating characteristic curve analysis and the area under the curve (AUC). RESULTS: Nine radiomics features with non-zero coefficients were included in the LASSO regression of the radiomics score (RAD score). Infarct size (odds ratio [OR]: 1.04 (1.00-1.07); P = 0.031) and RAD score (OR: 3.43 (2.34-5.28); P < 0.001) were independent predictors of LVAR. The RAD score predicted LVAR, with an AUC (95% confidence interval [CI]) of 0.82 (0.75-0.89) in the training set and 0.75 (0.62-0.89) in the testing set. Combining the RAD score with infarct size yielded favorable performance in predicting LVAR, with an AUC of 0.84 (0.72-0.95). Moreover, the addition of the RAD score to the left ventricular ejection fraction (LVEF) significantly increased the AUC from 0.68 (0.52-0.84) to 0.82 (0.70-0.93) (P = 0.018), which was also comparable to the prediction provided by the combined microvascular obstruction, infarct size, and LVEF with an AUC of 0.79 (0.65-0.94) (P = 0.727). CONCLUSION: Radiomics analysis using non-contrast cine CMR can predict LVAR after STEMI independently and incrementally to LVEF and may provide an alternative to traditional CMR parameters.
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ST Elevation Myocardial Infarction , Female , Humans , Infant, Newborn , Male , Cohort Studies , Magnetic Resonance Spectroscopy , Retrospective Studies , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Stroke Volume , Ventricular Function, LeftABSTRACT
OBJECTIVES: To evaluate the changes in cardiac magnetic resonance (CMR) characteristics and investigate the predictors of reverse left ventricular remodeling (r-LVR) in ST-segment elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: Eighty-six STEMI patients (median 56 years) were retrospectively studied. The patients were divided into r-LVR and without r-LVR groups. CMR analysis included LV volume, infarct characteristics, and global and regional myocardial function. The strain and displacement were assessed by CMR-feature tracking. The predictors of r-LVR were analyzed by the logistic regression method. RESULTS: There were 37 patients in the r-LVR group and 49 patients in the without r-LVR group. At initial CMR, there was no difference in LV volume and global cardiac function between the two groups. However, the infarct zone radial and longitudinal displacements were higher in the r-LVR group (p < 0.05, respectively). At the second CMR, the r-LVR group showed higher LVEF, lower LV volume, and total enhanced mass (all p < 0.05). The infarct zone radial and circumferential strains and radial displacement were higher in the r-LVR group (all p < 0.05). The r-LVR group had better recovery of myocardial injury and function. Of note, microvascular obstruction (MVO) mass (odds ratio: 0.779 (0.613-0.989), p = 0.041) and infarct zone peak longitudinal displacement (PLD) (odds ratio: 1.448 (1.044-2.008), p = 0.026) were independent predictors of r-LVR. CONCLUSIONS: At initial CMR, there were no differences in global cardiac function between the two groups, but infarct zone displacements were higher in the r-LVR group. The r-LVR group had better recovery of cardiac function. In addition, MVO mass and infarct zone PLD were independent predictors of r-LVR. CLINICAL RELEVANCE STATEMENT: Our study assessed changes in cardiac structure, function, and tissue characteristics after STEMI by CMR, investigated the best predictors of r-LVR in STEMI patients, and laid the foundation for the development of new parameter-guided treatment strategies for STEMI patients. KEY POINTS: ⢠At initial CMR, the reverse left ventricular remodeling (r-LVR) group had less myocardial damage and higher infarct zone displacement, but there were no differences in global function between the two groups. ⢠Both groups showed recovery of myocardial injury and cardiac function over time, but the r-LVR group had less enhanced mass and better cardiac function compared to the without r-LVR group at the second CMR. ⢠Microvascular obstruction mass and infarct zone peak longitudinal displacement by cardiac magnetic resonance feature-tracking were significant predictors of r-LVR in STEMI patients.
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Retrospective Studies , Ventricular Remodeling , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Ventricular Function, Left , Magnetic Resonance Imaging, Cine , Stroke VolumeABSTRACT
Tailored hydration strategies appear to provide an effective solution for preventing contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). The Vigileo/FloTrac system could predict the patients' fluid responsiveness and tolerance to hydration. This prospective multicenter, randomized controlled, open-label study evaluated the efficacy of aggressive hydration guided by the Vigileo/FloTrac system for CIN prevention in patients with acute myocardial infarction (AMI). This trial enrolled patients with AMI undergoing urgent PCI, and these patients were randomized (1:1) to receive either aggressive hydration guided by Vigileo/FloTrac system (intervention group) or general hydration (control group). Patients with AMI in the intervention group received a loading dose of saline, and the hydration speed was adjusted according to the change of Vigileo/FloTrac index. The primary end point is CIN, which was defined as a >25% or >0.5 mg/100 ml increase in serum creatinine compared with baseline during the first 72 hours after urgent PCI. This trial was registered in ClinicalTrials.gov (NCT04382313). A total of 344 patients with AMI were enrolled and randomized in our trial, and the baseline characteristics, including risk factors of CIN, of the Vigileo/FloTrac-guided hydration group (n = 173) and control group (n = 171) were well balanced (all p >0.05). The total hydration volume in Vigileo/FloTrac-guided hydration group was significantly much more than control group (1,910 ± 600 vs 440 ± 90 ml, p <0.001). The incidence of CIN in the Vigileo/FloTrac-guided hydration group was significantly decreased than that in the control group (12.1% [21/173] vs 22.2% [38/171], p = 0.013). There was not significantly different in the incidence of acute heart failure after PCI (9.2% [16/173] vs 7.6% [13/171], p = 0.583). The incidence of main adverse cardiovascular events in the Vigileo/FloTrac-guided hydration group was lower than that in the control group but without statistically difference (30 events [17.3%] vs 38 events [22.2%], p = 0.256). In conclusion, Vigileo/FloTrac system-guided aggressive hydration could effectively decrease the risk of CIN for patients with AMI undergoing urgent PCI and avoid attack of acute heart failure at the same time.
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Acute Kidney Injury , Heart Failure , Kidney Diseases , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Contrast Media/adverse effects , Prospective Studies , Fluid Therapy/adverse effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Acute Kidney Injury/epidemiology , Myocardial Infarction/complications , Kidney Diseases/epidemiology , Heart Failure/complications , CreatinineABSTRACT
BACKGROUND: Cardiac magnetic resonance imaging (CMR) is the gold standard for measuring infarct size (IS). However, this method is expensive and requires a specially trained technologist to administer. We therefore sought to quantify the IS using machine learning (ML) based analysis on clinical features, which is a convenient and cost-effective alternative to CMR. METHODS AND RESULTS: We included 315 STEMI patients with CMR examined one week after morbidity in final analysis. After feature selection by XGBoost on fifty-six clinical features, we used five ML algorithms (random forest (RF), light gradient boosting decision machine, deep forest, deep neural network, and stacking) to predict IS with 26 (selected by XGBoost with information gain greater than average level of 56 features) and the top 10 features, during which 5-fold cross-validation were used to train and optimize models. We then evaluated the value of actual and ML-IS for the prediction of adverse remodeling. Our finding indicates that MLs outperform the linear regression in predicting IS. Specifically, the RF with five predictors identified by the exhaustive method performed better than linear regression (LR) with 10 indicators (R2 of RF: 0.8; LR: 0). The finding also shows that both actual and ML-IS were independently associated with adverse remodeling. ML-IS ≥ 21% was associated with a twofold increase in the risk of LV remodeling (P < 0.01) compared with patients with reference IS (1st tertile). CONCLUSION: ML-based methods can predict IS with widely available clinical features, which provide a proof-of-concept tool to quantitatively assess acute phase IS.
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/etiology , Heart , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging, Cine/methods , Percutaneous Coronary Intervention/adverse effects , Ventricular Function, LeftABSTRACT
PURPOSE: Trimetazidine, a metabolic agent with anti-ischemic effects, was reported to reduce reperfusion injury in animal models. In this randomized double-blind placebo-controlled trial, we investigated the effects of trimetazidine on the reduction of infarction size in patients undergoing revascularization for ST segment elevation myocardial infarction (STEMI). METHODS: Patients with STEMI randomly received trimetazidine (n = 87) or placebo (n = 86) before primary percutaneous coronary intervention (PCI), and subsequently received oral trimetazidine or placebo for 12 months after reperfusion. The predefined primary endpoint was infarction size on cardiac magnetic resonance (CMR) performed at 7 days after primary PCI. The trial was registered on www. CLINICALTRIALS: gov (registration number: NCT02826616). RESULTS: The clinical characteristics of the patients in both groups were well-matched at baseline. At 7 days after primary PCI, the percentage and absolute infarction size in the trimetazidine group were significantly smaller than those in the control group (22% ± 12% [n = 74] vs. 27% ± 13% [n = 74], p = 0.011 and 28 ± 18 g [n = 74] vs. 35 ± 19 g [n = 74], p = 0.022, respectively), and the incidence of myocardial microvascular obstruction (MVO) measured by CMR was significantly reduced in the trimetazidine group (29.7% [22/74] vs. 52.7% [39/74], p = 0.005). The myocardial salvage index (MSI) measured by CMR was significantly higher in the trimetazidine group (48% ± 20% vs. 39% ± 20%, p = 0.008). The incidence of readmission due to aggravated heart failure did not differ significantly between the trimetazidine group and the control group (8.0% vs. 14.0%, p = 0.234). CONCLUSIONS: In patients with STEMI undergoing primary PCI, early trimetazidine before reperfusion reduced myocardial infarction size and MVO, and improved MSI.
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Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Trimetazidine , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Trimetazidine/adverse effects , Percutaneous Coronary Intervention/adverse effects , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/drug therapy , Myocardium/pathology , Treatment OutcomeABSTRACT
AIM: To investigate the impact of meteorological factors in different environments in the eastern and western regions of China on the incidence of lipid-abnormal dry eye.METHODS: This is a multicenter retrospective study. From March 1, 2021 to February 28, 2022, all patients with dry eye were selected from the ophthalmology clinic of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine and Friendship Hospital of Xinjiang Yili Kazakh Autonomous Prefecture. General data(gender, age, employment and education)and climate data for outdoor environments(temperature, humidity, air quality index and wind)on the day of the visit were collected. Patients who met the inclusion and exclusion criteria were selected. Single factor, multiple factors and nonlinear model analysis were applied to identify environmental factors of lipid-abnormal dry eye in both regions.RESULTS: There was no significant difference in the incidence of lipid-abnormal dry eye between Nanjing and Yili in different seasons. The incidence of lipid-abnormal dry eye in Yili was significantly higher in all seasons than in Nanjing(P&#x003C;0.001). The results of univariate research showed that the factors affecting the incidence of lipid-abnormal dry eye were gender, employment, humidity, air quality, and wind. The results of multivariate Logistic regression analysis showed that humidity, temperature and air quality were statistically significant, and remained significant after adjusting for the three confounding factors of age, gender and employment situation. Nonlinear analysis showed that the probability of lipid-abnormal dry eye increased with the decrease of temperature when the temperature was below 10℃; within the range of 10℃~15℃, the probability of lipid-abnormal dry eye tended to stabilize. When the temperature exceeded 15℃, the probability of lipid-abnormal dry eye increased with the increase of temperature. Humidity was negatively correlated with the onset of lipid-abnormal dry eye. As humidity increased, the probability of lipid-abnormal dry eye decreased.CONCLUSIONS: The risk of lipid-abnormal dry eye in Yili is higher than that in Nanjing throughout the four seasons. Humidity, temperature, air quality and other environmental and meteorological factors can all affect the incidence of lipid-abnormal dry eye.
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Objective:To explore the mechanism of Yiqi Yangyin decoction in the treatment of thyroid cancer by means of network pharmacology and molecular docking technique.Meth-ods:the chemical constituents of 10 kinds of Yiqi Yangyin decoction were searched by HERB database,the active components were screened by PubChem and SwissADNE,and the action targets of active components were predicted by Swisstargetprediction.The disease targets after operation of thyroid cancer were obtained by searching the databases of GeneCards,OMIM,Dis-GeNET and DrugBank.The intersection target of drug and disease was obtained by Venny2.1.0 platform,the intersection target protein interaction network was constructed by String database,and the core target protein was screened by Cytoscape3.9.1,the drug-active ingredient-target network map was constructed by Cytoscape3.9.1,and the key active components were obtained;the enrichment analysis of GO and KEGG was carried out using Metascape database;and the molecular docking verification of key targets and key components was carried out.Results:157active components of Yiqi Yangyin decoction were obtained,and 507targets of active compo-nents were predicted,1817 targets of thyroid cancer-related diseases and 154targets of drug-disease intersection were obtained.The key target genes of SRC,HSP90AA1,PIK3R1,PIK3CA and AKT1 were obtained by PPI analysis.Quercetin,kaempferol and luteolin were the key active components.Molecular docking showed that the key targets and key active components had good affinity.KEGG enrichment analysis showed that cancer pathway,PI3K-Akt pathway and HIF-1 pathway were the key pathways of drug action.Conclusion:Yiqi Yangyin decoction can play a therapeutic role in anti-inflammation,anti-tumor and improving tissue microenvironment with multi-components,multi-targets and multi-pathways.
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Objective To analyze the data of percutaneous coronary stent implantation related groups in certain hospi-tal of Beijing,so as to provide data support for promoting CHS-DRG payment reform and provide guidance and reference for its refined management.Methods The case data of local medical insurance patients in Beijing who received percutaneous coronary stent implantation from January 2020 to December 2021 in certain hospital were statistically analyzed,collect the medical insurance settlement information of the selected patients,and analyze the factors that affect their entry into FM19 group settlement.Results There are differences in the factors affecting FM19 inclusion in different reform stages,overtransfer personnel is a new independent factor that interferes with the group settlement in the actual operation stage.Some special operation codes may interfere with cases entering FM19 group due to pri-ority effect among disease groups.Conclusion The grouping settlement conditions of CHS-DRG are more complex,patients with different expense types need to be specifically analyzed according to the current grouping scheme and reimbursement policy.At present,there are relatively few disease groups settled by package for urban residents,and they continue to be affected by the rule of grouping priority.However,it is necessary to fully implement and strengthen the cost control of disease groups for urban employees,and rationally optimize the diagnosis and treat-ment plan to finely control medical costs.
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Background Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double-blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results A total of 238 patients with ST-segment-elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6-mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g; P=0.022), and the effect remained significant on long-term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g; P=0.008). The incidence of no-reflow/slow-flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118]; P=0.001), and thus, complete ST-segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118]; P=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%; P=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%; P=0.009) after reperfusion. Conclusions In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST-segment-elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03445728.
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Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/drug therapy , Nicorandil/therapeutic use , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/therapy , Stroke Volume , Treatment Outcome , Ventricular Function, LeftABSTRACT
Background: To analyze the relationship between left ventricular (LV) myocardial strain and transmurality of myocardial infarction at three circular sections (basal, mid-ventricular, apical) by a combined analysis of cardiac magnetic resonance feature tracking (CMR-FT) and late gadolinium enhancement (LGE) information in a cohort of ST-elevation acute myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PPCI). Methods: In all, 136 patients with STEMI who underwent PPCI within 12 hours of symptom onset were included. CMR-FT and LGE-MRI were performed 5±2 days after PCI for measuring regional and global myocardial strain indexes and transmural extent. Multivariate regression analysis and Kaplan-Meier survival analysis were performed. Results: Regional radial and circumferential strain decreased with increasing transmurality of myocardial infarction irrespective of basal, mid-ventricular, or apical segments. Segmental longitudinal strain was significantly decreased in the transmural infarcted segments only at the apical and mid-ventricular levels. A significant correlation was found between the number of transmural infarcts and global strain parameters in the apical and mid-ventricular portions. Transmural infarcted segments in apical + mid-ventricular portions >2 was related to an increased risk of cardiac events in patients with STEMI following PPCI than those ≤2. GLS was found to be an independent predictor of cardiac events in these patients. Conclusions: The number of transmural infarcted segments in apical + mid-ventricular portions affects LV global function and prognosis. Global longitudinal strain (GLS) is a significant predictor of adverse events after PPCI for STEMI. Morphologic and functional data fused to study complex pathophysiologic processes of LV early after STEMI may help in risk stratification of patients.
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The coronary arteries mainly function to perfuse the myocardium. When coronary artery resistance increases, myocardial perfusion decreases and myocardial remodeling occurs. Mitochondrial damage has been regarded as the primary cause of microvascular dysfunction. In the present study, we explored the effects of mitophagy activation on microvascular damage. Hypoxia/reoxygenation injury induced mitochondrial oxidative stress, thereby promoting mitochondrial dysfunction in endothelial cells. Mitochondrial impairment induced apoptosis, reducing the viability and proliferation of endothelial cells. However, supplementation with the mitophagy inducer urolithin A (UA) preserved mitochondrial function by reducing mitochondrial oxidative stress and stabilizing the mitochondrial membrane potential in endothelial cells. UA also sustained the viability and improved the proliferative capacity of endothelial cells by suppressing apoptotic factors and upregulating cyclins D and E. In addition, UA inhibited mitochondrial fission and restored mitochondrial fusion, which reduced the proportion of fragmented mitochondria within endothelial cells. UA enhanced mitochondrial biogenesis in endothelial cells by upregulating sirtuin 3 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha. These results suggested that activation of mitophagy may reduce hypoxia/reoxygenation-induced cardiac microvascular damage by improving mitochondrial quality control and increasing cell viability and proliferation.
Subject(s)
Endothelial Cells , Mitophagy , Endothelial Cells/metabolism , Humans , Hypoxia/metabolism , Ischemia/metabolism , Mitochondria , Mitophagy/physiology , ReperfusionABSTRACT
Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.
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Mitochondria-derived peptides (MDPs) are a new class of bioactive peptides encoded by small open reading frames (sORFs) within known mitochondrial DNA (mtDNA) genes. MDPs may affect the expression of nuclear genes and play cytoprotective roles against chronic and age-related diseases by maintaining mitochondrial function and cell viability in the face of metabolic stress and cytotoxic insults. In this review, we summarize clinical and experimental findings indicating that MDPs act as local and systemic regulators of glucose homeostasis, immune and inflammatory responses, mitochondrial function, and adaptive stress responses, and focus on evidence supporting the protective effects of MDPs against myocardial infarction. These insights into MDPs actions suggest their potential in the treatment of cardiovascular diseases and should encourage further research in this field.
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A variety of complex risk factors and pathological mechanisms contribute to myocardial stress, which ultimately promotes the development of cardiovascular diseases, including acute cardiac insufficiency, myocardial ischemia, myocardial infarction, high-glycemic myocardial injury, and acute alcoholic cardiotoxicity. Myocardial stress is characterized by abnormal metabolism, excessive reactive oxygen species production, an insufficient energy supply, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. Mitochondria, the main organelles contributing to the energy supply of cardiomyocytes, are key determinants of cell survival and death. Mitophagy is important for cardiomyocyte function and metabolism because it removes damaged and aged mitochondria in a timely manner, thereby maintaining the proper number of normal mitochondria. In this review, we first introduce the general characteristics and regulatory mechanisms of mitophagy. We then describe the three classic mitophagy regulatory pathways and their involvement in myocardial stress. Finally, we discuss the two completely opposite effects of mitophagy on the fate of cardiomyocytes. Our summary of the molecular pathways underlying mitophagy in myocardial stress may provide therapeutic targets for myocardial protection interventions.
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A major shortcoming of postischemic therapy for myocardial infarction is the no-reflow phenomenon due to impaired cardiac microvascular function including microcirculatory barrier function, loss of endothelial activity, local inflammatory cell accumulation, and increased oxidative stress. Consequently, inadequate reperfusion of the microcirculation causes secondary ischemia, aggravating the myocardial reperfusion injury. ATP-sensitive potassium ion (KATP) channels regulate the coronary blood flow and protect cardiomyocytes from ischemia-reperfusion injury. Studies in animal models of myocardial ischemia-reperfusion have illustrated that the opening of mitochondrial KATP (mito-KATP) channels alleviates endothelial dysfunction and reduces myocardial necrosis. By contrast, blocking mito-KATP channels aggravates microvascular necrosis and no-reflow phenomenon following ischemia-reperfusion injury. Nicorandil, as an antianginal drug, has been used for ischemic preconditioning (IPC) due to its mito-KATP channel-opening effect, thereby limiting infarct size and subsequent severe ischemic insult. In this review, we analyze the protective actions of nicorandil against microcirculation reperfusion injury with a focus on improving mitochondrial integrity. In addition, we discuss the function of mitochondria in the pathogenesis of myocardial ischemia.
Subject(s)
Microcirculation/drug effects , Mitochondria/drug effects , Myocardial Reperfusion Injury/drug therapy , Nicorandil/pharmacology , Oxidative Stress/drug effects , Animals , Humans , Mitochondria/metabolism , Myocardial Ischemia/drug therapyABSTRACT
BACKGROUND: Reduced forced expiratory flow between 25% and 75% of vital capacity percent predicted (FEF25-75%) representing small airway dysfunction (SAD) was associated with asthma development and progression. OBJECTIVE: To investigate whether FEF25-75% was superior to forced expiratory volume in 1 second in predicted (FEV1%) in reflecting asthma features in adult patients. METHODS: A retrospective spirometry dataset comprising 1801 adult patients with confirmed asthma and a subgroup of 332 patients having detailed clinical data were used to explore the association of FEF25-75% and/or FEV1% with clinical features of asthma. RESULTS: Of the 1801 subjects, FEV1% and FEF25-75% ranged from 136.8% to 10.2% and 127.3% to 3.1%, respectively. FEF25-75% < 65% was present in 1,478 (82.07%) of patients. FEF25-75% was strongly correlated with matched FEV1% (r = 0.900, P < .001). FEF25-75% and FEV1% were both correlated with airway hyperresponsiveness (r = 0.436, P < .001; r = 0.367, P < .001), asthma control test score (r = 0.329, P < .001; r = 0.335, P < .001), and sputum eosinophil count (r = -0.306, P < .001; r = -0.307, P < .001). Receiver-operating characteristic curves showed that FEF25-75% had greater value in predicting severe asthma (area under the curve: 0.84 vs 0.81, P = .018), airflow obstruction (0.97 vs 0.89, P < .001), and severe bronchial hyperresponsiveness (0.74 vs 0.69, P = .012) as compared with FEV1%. Patients with SAD (FEF25-75% < 65%) in the presence of normal FEV1% exhibited higher sputum eosinophil counts and had an increased dosage of daily inhaled corticosteroids (P < .001 and P = .010) than patients with normal lung function and their FEF25-75% values correlated with sputum eosinophil count (r = -0.419, P = .015), but not FEV1%. CONCLUSION: FEF25-75% represented small airway function and was more sensitive at reflecting airway hyperresponsiveness, inflammation, and disease severity as compared with FEV1% in patients with asthma. Our data suggest further assessment of FEF25-75% in asthma management, particularly for those with SAD who present normal FEV1%.
Subject(s)
Asthma , Bronchial Hyperreactivity , Adult , Asthma/diagnosis , Asthma/epidemiology , Forced Expiratory Volume , Humans , Respiratory Function Tests , Retrospective Studies , SpirometryABSTRACT
Previous studies have shown that nicorandil has a protective effect on cardiomyocytes. However, there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) compared to the current standard of percutaneous coronary intervention (PCI) regimen. The CHANGE (China-Admini stration of Nicorandil Group) study is a multicenter, prospective, randomized, double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China, aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocar dial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.