Assessment of adverse events of the novel cardiovascular drug vericiguat: a real-world pharmacovigilance study based on FAERS.

BACKGROUND: This study aims to analyze the adverse event reports (AERs) to vericiguat using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) and provide evidence for the clinical use. METHODS: AERs due to vericiguat from 2021Q1 to 2024Q1 identified as the primary suspect were screened, with duplicate reports subsequently eliminated. Various quantitative signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were then employed for data mining and analysis. Signal strength is represented by the 95% confidence interval, information component (IC), and empirical Bayesian geometric mean (EBGM). RESULTS: A total of 617 vericiguat-related AERs were identified. Strong signals were observed in 21 system organ classes. Furthermore, the most frequently reported preferred terms (PT) was hypotension (n = 86, ROR 25.92, PRR 24.11, IC 4.59, EBGM 24.07), followed by dizziness (n = 52, ROR 6.44, PRR 6.20, IC 2.63, EBGM 6.20), malaise (n = 25, ROR 3.59, PRR 3.54, IC 1.82, EBGM 3.54), blood pressure decreased (n = 23, ROR 20.00, PRR 19.64, IC 4.29, EBGM 19.61), and anemia (n = 21, ROR 6.67, PRR 6.57, IC 2.72, EBGM 6.57). CONCLUSIONS: This study extended the adverse reactions documented in the FDA instruction and provided supplementary evidence regarding the clinical safety of vericiguat.

Multi-omics analysis reveals that Cas13d contributes to PI3K-AKT signaling and facilitates cell proliferation via PFKFB4 upregulation.

The CRISPR-Cas system is a powerful gene editing technology, the clinical application of which is currently constrained due to safety concerns. A substantial body of safety research concerning Cas9 exists; however, scant attention has been directed toward investigating the safety profile of the emergent Cas13 system, which confers RNA editing capabilities. In particular, uncertainties persist regarding the potential cellular impacts of Cas13d in the absence of reliance on a cleavage effect. In this study, we conducted an initial exploration of the effects of Cas13d on HeLa cells. Total RNA and protein samples were extracted after transfection with a Cas13d-expressing plasmid construct, followed by transcriptomic and proteomic sequencing. Differential gene expression analysis identified 94 upregulated and 847 downregulated genes, while differential protein expression analysis identified 185 upregulated and 231 downregulated proteins. Subsequently, enrichment analysis was conducted on the transcriptome and proteome sequencing data, revealing that the PI3K-Akt signaling pathway is a common term. After intersecting the differentially expressed genes enriched in the PI3K-Akt signaling pathway with all the differentially expressed proteins, it was found that the expression of the related regulatory gene PFKFB4 was upregulated. Moreover, western blot analysis demonstrated that Cas13d can mediate PI3K-Akt signaling upregulation through overexpression of PFKFB4. CCK-8 assay, colony formation, and EdU experiments showed that Cas13d can promote cell proliferation. Our data demonstrate, for the first time, that Cas13d significantly impacts the transcriptomic and proteomic profiles, and proliferation phenotype, of HeLa cells, thus offering novel insights into safety considerations regarding gene editing systems.

CircCHSY1 protects hearts against ischemia/reperfusion injury by enhancing heme oxygenase 1 expression via miR-24-3p.

AIMS: Circular RNAs are important players involving in a variety of physiological and pathological processes. However, their functions and mechanisms during myocardial ischemic injury and protection remain largely unknown. We recently found significant alterations of many circRNAs including circCHSY1 following myocardial ischemia/reperfusion (I/R) injury, whereas their exact functions are unclear. Here, we investigated roles of circCHSY1 in the acute myocardial I/R injury and the potential mechanisms involved. METHODS AND RESULTS: The expression of circCHSY1 was detected in cardiomyocytes from mouse, rat and human embryonic stem cells (hESC-CMs). It was further upregulated in mouse I/R (30 min/24 h) hearts, oxygen glucose deprivation/reperfused (OGD/R, 6 h/2 h) primary neonatal rat ventricular cardiomyocytes (NRCMs) and OGD/R (48 h/2 h) hESC-CMs. Adenovirus-mediated circCHSY1-overexpression significantly decreased infarct size and lactate dehydrogenase (LDH) release in mouse I/R hearts. Consistently, circCHSY1 overexpression reduced the LDH release in the OGD/R NRCMs and hESC-CMs, improved cell viability, and preserved mitochondrial function in the OGD/R NRCMs, whereas there were no significant differences in cell viability and LDH release between the OGD/R NRCMs with and without siRNA-mediated circCHSY1 knockdown. Mechanistically, circCHSY1 was detected to bind with miR-24-3p analyzed by dual luciferase assay and RNA pull-down assays. CircCHSY1 overexpression-mediated protective effects on cells and mitochondria in OGD/R NRCMs were reversed by the miR-24-3p mimic. Further, dual luciferase assay showed that miR-24-3p directly bound to heme oxygenase 1 (HO1) via its 3'UTR. The protein level of HO1 was downregulated by miR-24-3p mimic in OGD/R NRCMs but enhanced by the circCHSY1 overexpression in vitro and in vivo. Functionally, the HO1 knockdown by adenovirus in vivo and by siRNA in vitro eliminated cardioprotective effects of circCHSY1 overexpression. CONCLUSION: CircCHSY1 is upregulated following myocardial I/R injury. The higher level of circCHSY1 protects I/R hearts and cardiomyocytes. The protection of circCHSY1 is mediated through enhancement of the HO1 level, resulting in preserving mitochondrial homeostasis via targeting miR-24-3p in cardiomyocytes. These findings suggest circCHSY1 as a protective factor.

Genetic Causality between Type 1 Diabetes and Arrhythmia Identified by a Two-sample Mendelian Randomization Study.

BACKGROUND: Clinical studies have shown that cardiovascular diseases in patients with type 1 diabetes (T1D) are often atypical or asymptomatic. The link between T1D and arrhythmia remains unclear. To infer causality between T1D and arrhythmia at the genetic level, we conducted a Mendelian randomization study through the genetic tools of T1D. METHODS: In this study, we used genetic variables and summary statistics from genome-wide association studies of T1D and arrhythmia. Single nucleotide polymorphisms were selected based on the assumptions of instrumental variables. The inverse variance-weighted method was used as the primary analysis to summarize the causal effects between exposure and outcome. The weighted median and weighted mode methods were used as secondary methods. We tested for horizontal pleiotropy using the MR-Egger method and detected heterogeneity using the Q-test. A leave-one-out sensitivity analysis was performed. Scatter plots, forest plots, and funnel plots were used to visualize the results of the MR analysis. RESULTS: In this study, we selected 28 T1D-related SNPs as instrumental variables. The IVW [odds ratio (OR) = 0.98, 95 % confidence interval (CI) = 0.97-1.00, P = 0.008], weighted median (OR = 0.98, 95 % CI = 0.96 - 0.99, P = 0.009), and weighted mode (OR = 0.98, 95 % CI = 0.96-0.99, P = 0.018) analysis methods suggested a causal effect of T1D on arrhythmia. The MR-Egger method indicated no horizontal pleiotropy (P = 0.649), and the Q-test showed no heterogeneity (IVW, P = 0.653). CONCLUSIONS: Our MR analysis revealed a causal association between T1D and the development of arrhythmia, indicating that patients with T1D had a higher risk of arrhythmia.

Identification of Shared Signature Genes and Immune Microenvironment Subtypes for Heart Failure and Chronic Kidney Disease Based on Machine Learning.

Background: A complex interrelationship exists between Heart Failure (HF) and chronic kidney disease (CKD). This study aims to clarify the molecular mechanisms of the organ-to-organ interplay between heart failure and CKD, as well as to identify extremely sensitive and specific biomarkers. Methods: Differentially expressed tandem genes were identified from HF and CKD microarray datasets and enrichment analyses of tandem perturbation genes were performed to determine their biological functions. Machine learning algorithms are utilized to identify diagnostic biomarkers and evaluate the model by ROC curves. RT-PCR was employed to validate the accuracy of diagnostic biomarkers. Molecular subtypes were identified based on tandem gene expression profiling, and immune cell infiltration of different subtypes was examined. Finally, the ssGSEA score was used to build the ImmuneScore model and to assess the differentiation between subtypes using ROC curves. Results: Thirty-three crosstalk genes were associated with inflammatory, immune and metabolism-related signaling pathways. The machine-learning algorithm identified 5 hub genes (PHLDA1, ATP1A1, IFIT2, HLTF, and MPP3) as the optimal shared diagnostic biomarkers. The expression levels of tandem genes were negatively correlated with left ventricular ejection fraction and glomerular filtration rate. The CIBERSORT results indicated the presence of severe immune dysregulation in patients with HF and CKD, which was further validated at the single-cell level. Consensus clustering classified HF and CKD patients into immune and metabolic subtypes. Twelve immune genes associated with immune subtypes were screened based on WGCNA analysis, and an ImmuneScore model was constructed for high and low risk. The model accurately predicted different molecular subtypes of HF or CKD. Conclusion: Five crosstalk genes may serve as potential biomarkers for diagnosing HF and CKD and are involved in disease progression. Metabolite disorders causing activation of a large number of immune cells explain the common pathogenesis of HF and CKD.

Calpain inhibition protects against atrial fibrillation by mitigating diabetes-associated atrial fibrosis and calcium handling dysfunction in type 2 diabetes mice.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for atrial structural remodeling and atrial fibrillation (AF). Calpain activity is hypothesized to promote atrial remodeling and AF. OBJECTIVE: The purpose of this study was to investigate the role of calpain in diabetes-associated AF, fibrosis, and calcium handling dysfunction. METHODS: DM-associated AF was induced in wild-type (WT) mice and in mice overexpressing the calpain inhibitor calpastatin (CAST-OE) using high-fat diet feeding followed by low-dose streptozotocin injection (75 mg/kg). DM and AF outcomes were assessed by measuring blood glucose levels, fibrosis, and AF susceptibility during transesophageal atrial pacing. Intracellular Ca2+ transients, spontaneous Ca2+ release events, and intracellular T-tubule membranes were measured by in situ confocal microscopy. RESULTS: WT mice with DM had significant hyperglycemia, atrial fibrosis, and AF susceptibility with increased atrial myocyte calpain activity and Ca2+ handling dysfunction relative to control treated animals. CAST-OE mice with DM had a similar level of hyperglycemia as diabetic WT littermates but lacked significant atrial fibrosis and AF susceptibility. DM-induced atrial calpain activity and downregulation of the calpain substrate junctophilin-2 were prevented by CAST-OE. Atrial myocytes of diabetic CAST-OE mice exhibited improved T-tubule membrane organization, Ca2+ handling, and reduced spontaneous Ca2+ release events compared to littermate controls. CONCLUSION: This study confirmed that DM promotes calpain activation, atrial fibrosis, and AF in mice. CAST-OE effectively inhibits DM-induced calpain activation and reduces atrial remodeling and AF incidence through improved intracellular Ca2+ homeostasis. Our results support calpain inhibition as a potential therapy for preventing and treating AF in DM patients.

Hydrogen-rich saline alleviates cardiomyocyte apoptosis by reducing expression of calpain1 via miR-124-3p.

AIMS: Molecular hydrogen has been exhibited a protective function in heart diseases. Our previous study demonstrated that hydrogen-rich saline (HRS) could scavenge free radicals selectively and alleviate the inflammatory response in the myocardial ischaemia/reperfusion (I/R) injury, but the underlying mechanism has not been fully clarified. METHODS AND RESULTS: Adult (10 weeks) C57BL/6 male mice and neonatal rat cardiomyocytes were used to establish I/R and hypoxia/reoxygenation (H/R) injury models. I/R and H/R models were treated with HRS to classify the mechanisms of cardioproctective function. In this study, we found that miR-124-3p was significantly decreased in both I/R and H/R models, while it was partially ameliorated by HRS pretreatment. HRS treatment also alleviated ischaemia-induced apoptotic cell death and increased cell viability during I/R process, whereas silencing expression of miR-124-3p abolished this protective effect. In addition, we identified calpain1 as a direct target of miR-124-3p, and up-regulation of miR-124-3 produced both activity and expression of calpain1. It was also found that compared with the HRS group, overexpression of calpain1 increased caspase-3 activities, promoted cleaved-caspase3 and Bax protein expressions, and correspondingly decreased Bcl-2, further reducing cell viability. These results illustrated that calpain1 overexpression attenuated protective effect of HRS on cardiomyocytes in H/R model. CONCLUSIONS: The present study showed a protective effect of HRS on I/R injury, which may be associated with miR-124-3p-calpain1 signalling pathway.

Phenotyping cardiogenic shock that showed different clinical outcomes and responses to vasopressor use: a latent profile analysis from MIMIC-IV database.

Background: Cardiogenic shock (CS) is increasingly recognized as heterogeneous in its severity and response to therapies. This study aimed to identify CS phenotypes and their responses to the use of vasopressors. Method: The current study included patients with CS complicating acute myocardial infarction (AMI) at the time of admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Laboratory and clinical variables were collected and used to conduct latent profile (LPA) analysis. Furthermore, we used a multivariable logistic regression (LR) model to explore the independent association between the use of vasopressors and endpoints. Result: A total of 630 eligible patients with CS after AMI were enrolled in the study. The LPA identified three profiles of CS: profile 1 (n = 259, 37.5%) was considered as the baseline group; profile 2 (n = 261, 37.8%) was characterized by advanced age, more comorbidities, and worse renal function; and profile 3 (n = 170, 24.6%) was characterized by systemic inflammatory response syndrome (SIRS)-related indexes and acid-base balance disturbance. Profile 3 showed the highest all-cause in-hospital mortality rate (45.9%), followed by profile 2 (43.3%), and profile 1 (16.6%). The LR analyses showed that the phenotype of CS was an independent prognostic factor for outcomes, and profiles 2 and 3 were significantly associated with a higher risk of in-hospital mortality (profile 2: odds ratio [OR] 3.95, 95% confidence interval [CI] 2.61-5.97, p < 0.001; profile 3: OR 3.90, 95%CI 2.48-6.13, p < 0.001) compared with profile 1. Vasopressor use was associated with an improved risk of in-hospital mortality for profile 2 (OR: 2.03, 95% CI: 1.15-3.60, p = 0.015) and profile 3 (OR: 2.91, 95% CI: 1.02-8.32, p = 0.047), respectively. The results of vasopressor use showed no significance for profile 1. Conclusion: Three phenotypes of CS were identified, which showed different outcomes and responses to vasopressor use.

A nomogram for predicting postoperative overall survival of patients with lung squamous cell carcinoma: A SEER-based study.

Background: Lung squamous cell carcinoma (LSCC) is a common subtype of non-small cell lung cancer. Our study aimed to construct and validate a nomogram for predicting overall survival (OS) for postoperative LSCC patients. Methods: A total of 8,078 patients eligible for recruitment between 2010 and 2015 were selected from the Surveillance, Epidemiology, and End Results database. Study outcomes were 1-, 2- and 3-year OS. Analyses performed included univariate and multivariate Cox regression, receiver operating characteristic (ROC) curve construction, calibration plotting, decision curve analysis (DCA) and Kaplan-Meier survival plotting. Results: Seven variables were selected to establish our predictive nomogram. Areas under the ROC curves were 0.658, 0.651 and 0.647 for the training cohort and 0.673, 0.667 and 0.658 for the validation cohort at 1-, 2- and 3-year time-points, respectively. Calibration curves confirmed satisfactory consistencies between nomogram-predicted and observed survival probabilities, while DCA confirmed significant clinical usefulness of our model. For risk stratification, patients were divided into three risk groups with significant differences in OS on Kaplan-Meier analysis (P < 0.001). Conclusion: Here, we designed and validated a prognostic nomogram for OS in postoperative LSCC patients. Application of our model in the clinical setting may assist clinicians in evaluating patient prognosis and providing highly individualized therapy.

Case report: Resection of a giant right ventricular myxoma.

Myxoma constitutes the main subtype of all benign cardiac tumors, tending to be more common in women and occurring mostly in the left and right atria. Its classic clinical presentations are intracardiac obstruction, embolization, and systemic or constitutional symptoms, such as fever, in decreasing order. Several imaging techniques such as echocardiography, computed tomography, and angiocardiography contribute to the diagnosis of myxoma, ruling out significant coronary diseases, and assessment of myocardial invasion and tumor involvement of adjacent structures. Surgical resection is the only effective therapeutic option for patients with cardiac myxoma. Here, we report a unique case of a middle-aged man who presented with a giant myxoma and a 3-day history of chest tightness and shortness of breath after physical activity. Subsequently, transthoracic echocardiography revealed a mass of solid echodensity located within the right ventricle, complicated by abnormal hemodynamics. A cardiac computed tomographic angiography showed a large homogeneous density filling defect consuming most parts of the right ventricle and protruding from beat to beat. A surgical resection and histological study later successfully confirmed the diagnosis, and the patient's postoperative recovery course was found to be uneventful.

Machine Learning Methods for Predicting Long-Term Mortality in Patients After Cardiac Surgery.

Objective: This study aims to construct and validate several machine learning (ML) algorithms to predict long-term mortality and identify risk factors in unselected patients post-cardiac surgery. Methods: The Medical Information Mart for Intensive Care (MIMIC-III) database was used to perform a retrospective administrative database study. Candidate predictors consisted of the demographics, comorbidity, vital signs, laboratory test results, scoring systems, and treatment information on the first day of ICU admission. Four-year mortality was set as the study outcome. We used the ML methods of logistic regression (LR), artificial neural network (NNET), naïve bayes (NB), gradient boosting machine (GBM), adapting boosting (Ada), random forest (RF), bagged trees (BT), and eXtreme Gradient Boosting (XGB). The prognostic capacity and clinical utility of these ML models were compared using the area under the receiver operating characteristic curves (AUC), calibration curves, and decision curve analysis (DCA). Results: Of 7,368 patients in MIMIC-III included in the final cohort, a total of 1,337 (18.15%) patients died during a 4-year follow-up. Among 65 variables extracted from the database, a total of 25 predictors were selected using recursive feature elimination and included in the subsequent analysis. The Ada model performed best among eight models in both discriminatory ability with the highest AUC of 0.801 and goodness of fit (visualized by calibration curve). Moreover, the DCA shows that the net benefit of the RF, Ada, and BT models surpassed that of other ML models for almost all threshold probability values. Additionally, through the Ada technique, we determined that red blood cell distribution width (RDW), blood urea nitrogen (BUN), SAPS II, anion gap (AG), age, urine output, chloride, creatinine, congestive heart failure, and SOFA were the Top 10 predictors in the feature importance rankings. Conclusions: The Ada model performs best in predicting 4-year mortality after cardiac surgery among the eight ML models, which might have significant application in the development of early warning systems for patients following operations.

Predictive value of lymphocyte-to-monocyte ratio in critically Ill patients with atrial fibrillation: A propensity score matching analysis.

BACKGROUND: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). Lymphocyte-to-monocyte ratio (LMR) has been proved to be a reliable predictor of many inflammation-associated diseases, but little data are available on the relationship between LMR and AF. We aimed to evaluate the predictive value of LMR in predicting all-cause mortality among AF patients. METHODS: Data of patients diagnosed with AF were retrieved from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. X-tile analysis was used to calculate the optimal cutoff value for LMR. The Cox regression model was used to assess the association of LMR and 28-day, 90-day, and 1-year mortality. Additionally, a propensity score matching (PSM) method was performed to minimize the impact of potential confounders. RESULTS: A total of 3567 patients hospitalized with AF were enrolled in this study. The X-tile software indicated that the optimal cutoff value of LMR was 2.67. A total of 1127 pairs were generated, and all the covariates were well balanced after PSM. The Cox proportional-hazards model showed that patients with the low LMR (≤2.67) had a higher 1-year all-cause mortality than those with the high LMR (>2.67) in the study cohort before PSM (HR = 1.640, 95% CI: 1.437-1.872, p < 0.001) and after PSM (HR = 1.279, 95% CI: 1.094-1.495, p = 0.002). The multivariable Cox regression analysis for 28-day and 90-day mortality yielded similar results. CONCLUSIONS: The lower LMR (≤2.67) was associated with a higher risk of 28-day, 90-day, and 1-year all-cause mortality, which might serve as an independent predictor in AF patients.

Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study.

BACKGROUND: The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data. METHODS: Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings. RESULTS: A total of 2922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1230/2922) patients were exposed to oxygen therapy, and 57.9% (1692/2922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality [odds ratio (OR) 1.30; 95% confidence interval (CI) 0.92-1.82; P = 0.138] or ICU mortality (OR 1.39; 95% CI 0.83-2.32; P = 0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06-1.15; P <  0.001) and hospital LOS (OR 1.06; 95% CI 1.01-1.10; P = 0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups. CONCLUSION: Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.

Admission Serum Ionized and Total Calcium as New Predictors of Mortality in Patients with Cardiogenic Shock.

BACKGROUND: Although serum calcium has been proven to be a predictor of mortality in a wide range of diseases, its prognostic value in critically ill patients with cardiogenic shock (CS) remains unknown. This retrospective observational study is aimed at investigating the association of admission calcium with mortality among CS patients. METHODS: Critically ill patients diagnosed with CS in the Medical Information Mart for Intensive Care-III (MIMIC-III) database were included in our study. The study endpoints included 30-day, 90-day, and 365-day all-cause mortalities. First, admission serum ionized calcium (iCa) and total calcium (tCa) levels were analyzed as continuous variables using restricted cubic spline Cox regression models to evaluate the possible nonlinear relationship between serum calcium and mortality. Second, patients with CS were assigned to four groups according to the quartiles (Q1-Q4) of serum iCa and tCa levels, respectively. In addition, multivariable Cox regression analyses were used to assess the independent association of the quartiles of iCa and tCa with clinical outcomes. RESULTS: A total of 921 patients hospitalized with CS were enrolled in this study. A nonlinear relationship between serum calcium levels and 30-day mortality was observed (all P values for nonlinear trend < 0.001). Furthermore, multivariable Cox analysis showed that compared with the reference quartile (Q3: 1.11 ≤ iCa < 1.17 mmol/L), the lowest serum iCa level quartile (Q1: iCa < 1.04 mmol/L) was independently associated with an increased risk of 30-day mortality (Q1 vs. Q3: HR 1.35, 95% CI 1.00-1.83, P = 0.049), 90-day mortality (Q1 vs. Q3: HR 1.36, 95% CI 1.03-1.80, P = 0.030), and 365-day mortality (Q1 vs. Q3: HR 1.28, 95% CI 1.01-1.67, P = 0.046) in patients with CS. CONCLUSIONS: Lower serum iCa levels on admission were potential predictors of an increased risk of mortality in critically ill patients with CS.

Dynamic monitoring of cardiac foreign body by perioperative echocardiography: A case study.

Cardiac foreign bodies, especially those with sharp tips, may lead to unpredictable complications, such as penetrating cardiac injuries. Yet there have not been many reports of penetrating cardiac injuries caused by a needle that migrates from the neck to the heart. We herein present a review of such a case, focusing on the dynamic monitoring by perioperative echocardiography. The needle was represented on the monitor as a linear artifact that had penetrated through the ventricular wall and caused increasing pericardial effusion. Fortunately, the needle was successfully removed before it completely entered the right ventricular cavity. In this case, perioperative echocardiography played a significant role in clinical emergency decision making.

Prehospital aortic blood flow control techniques for non-compressible traumatic hemorrhage.

Non-compressible hemorrhage in the junctional areas and torso could be life-threatening and its prehospital control remains extremely challenging. The aim of this review was to compare commonly used techniques for the control of non-compressible hemorrhage in prehospital settings, and thereby provide evidence for further improvements in emergency care of traumatic injuries. Three techniques were reviewed including external aortic compression (EAC), abdominal aortic junctional tourniquet (AAJT), and resuscitative endovascular balloon occlusion of the aorta (REBOA). In prehospital settings, all three techniques have demonstrated clinical effectiveness for the control of severe hemorrhage. EAC is a cost- and equipment-free, easy-to-teach, and immediately available technique. In contrast, AAJT and REBOA are expensive and require detailed instructions or systematic training. Compared with EAC, AAJT and REBOA have greater potentials in the management of traumatic hemorrhage. AAJT can be used not only in the junctional areas but also in pelvic and bilateral lower limb injuries. However, both AAJT and REBOA should be used for a limited time (less than 1 hour) due to possible consequences of ischemia and reperfusion. Compared with EAC and AAJT, REBOA is invasive, requiring femoral arterial access and intravascular guidance and inflation. Mortality from non-compressible hemorrhage could be reduced through the prehospital application of aortic blood flow control techniques. EAC should be considered as the first-line choice for many non-compressible injuries that cannot be managed with conventional junctional tourniquets. In comparison, AAJT or REBOA is recommended for better control of the aorta blood flow in prehospital settings. Although these three techniques each have advantages, their use in trauma is not widespread. Future studies are warranted to provide more data about their safety and efficacy.

Role of Hydrogen Sulfide in Myocardial Ischemia-Reperfusion Injury.

ABSTRACT: Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide and carbon monoxide, has been found as an important endogenous gasotransmitter in the last few decades, and it plays a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia-reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of I/R injury, such as S-sulfhydrated modification, antiapoptosis, effects on microRNA, bidirectional effect on autophagy, antioxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development, and the pharmacological characterization of H2S donor drugs have made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.

The Neutrophil Percentage-to-Albumin Ratio as a New Predictor of All-Cause Mortality in Patients with Cardiogenic Shock.

BACKGROUND: Although the neutrophil percentage-to-albumin ratio (NPAR) has proven to be a robust systemic inflammation-based predictor of mortality in a wide range of diseases, the prognostic value of the NPAR in critically ill patients with cardiogenic shock (CS) remains unknown. This study aimed at investigating the association between the admission NPAR and clinical outcomes in CS patients using real-world data. METHODS: Critically ill patients diagnosed with CS in the Medical Information Mart for Intensive Care-III (MIMIC-III) database were included in our study. The study endpoints included all-cause in-hospital, 30-day, and 365-day mortality in CS patients. First, the NPAR was analyzed as a continuous variable using restricted cubic spline Cox regression models. Second, X-tile analysis was used to calculate the optimal cut-off values for the NPAR and divide the cohort into three NPAR groups. Moreover, multivariable Cox regression analyses were used to assess the association of the NPAR groups with mortality. RESULTS: A total of 891 patients hospitalized with CS were enrolled in this study. A nonlinear relationship between the NPAR and in-hospital and 30-day mortality was observed (all P values for nonlinear trend<0.001). According to the optimal cut-off values by X-tile, NPARs were divided into three groups: group I (NPAR < 25.3), group II (25.3 ≤ NPAR < 34.8), and group III (34.8 ≤ NPAR). Multivariable Cox analysis showed that higher NPAR was independently associated with increased risk of in-hospital mortality (group III vs. group I: hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.72-3.92, P < 0.001), 30-day mortality (group III vs. group I: HR 2.42, 95% CI 1.65-3.54, P < 0.001), and 365-day mortality (group III vs. group I: HR 6.80, 95% CI 4.10-11.26, P < 0.001) in patients with CS. CONCLUSIONS: Admission NPAR was independently associated with in-hospital, 30-day, and 365-day mortality in critically ill patients with CS.

Admission oxygen saturation and all-cause in-hospital mortality in acute myocardial infarction patients: data from the MIMIC-III database.

BACKGROUND: Acute myocardial infarction (AMI) is mainly caused by a mismatch of blood oxygen supply and demand in the myocardium. However, several studies have suggested that excessively high or low arterial oxygen tension could have deleterious effects on the prognosis of AMI patients. Therefore, the relationship between blood oxygenation and clinical outcomes among AMI patients is unclear, and could be nonlinear. In the critical care setting, blood oxygen level is commonly measured continuously using pulse oximetry-derived oxygen saturation (SpO2). The present study aimed to determine the association between admission SpO2 levels and all-cause in-hospital mortality, and to elucidate the optimal SpO2 range with real-world data. METHODS: Patients diagnosed with AMI on admission in the Medical Information Mart for Intensive Care III (MIMIC-III) database were included. A generalized additive model (GAM) with loess smoothing functions was used to determine and visualize the nonlinear relationship between admission SpO2 levels within the first 24 hours after ICU admission and mortality. Moreover, the Cox regression model was constructed to confirm the association between SpO2 and mortality. RESULTS: We included 1,846 patients who fulfilled our inclusion criteria, among whom 587 (31.80%) died during hospitalization. The GAM showed that the relationship between admission SpO2 levels and all-cause in-hospital mortality among AMI patients was nonlinear, as a U-shaped curve was observed. In addition, the lowest mortality was observed for an SpO2 range of 94-96%. Adjusted multivariable Cox regression analysis confirmed that the admission SpO2 level of 94-96% was independently associated with decreased mortality compared to SpO2 levels <94% [hazard ratio (HR) 1.352; 95% confidence interval (CI): 1.048-1.715; P=0.028] and >96% (HR 1.315; 95% CI: 1.018-1.658; P=0.030). CONCLUSIONS: The relationship between admission SpO2 levels and all-cause in-hospital mortality followed a U-shaped curve among patients with AMI. The optimal oxygen saturation range was identified as an SpO2 range of 94-96%, which was independently associated with increased survival in a large and heterogeneous cohort of AMI patients.