Comparison of liberal versus restrictive transfusion strategies after hip surgery in patients with coronary artery disease: a post hoc analysis of the FOCUS trial.

BACKGROUND: There are no clear recommendations for optimal transfusion thresholds for patients with coronary artery disease who undergo noncardiac surgery. By comparing restrictive and liberal transfusion strategies for coronary artery disease combined with hip surgery, this study hopes to provide recommendations for transfusion strategies in this special population. METHODS: A total of 805 patients from the FOCUS trial (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) with coronary artery disease combined with hip surgery were divided into two groups based on transfusion thresholds: restricted transfusion (a hemoglobin level of 8 g/deciliter) and liberal transfusion (a hemoglobin threshold of 10 g/deciliter). The primary outcome of this study was a composite endpoint including in-hospital death, myocardial infarction, unstable angina, and acute heart failure. The secondary endpoints included other in-hospital adverse events and 30- and 60-day follow-up events. Analyses were performed by intention to treat. RESULTS: Except for the proportion of congestive heart failure patients, the baseline levels of the two groups were comparable. The median number of transfusion units in the liberal transfusion group was 2 units, and the median transfusion volume in the restricted transfusion group was 0 units. The primary outcome was not significantly different between the two groups (9.2% vs. 9.4%, p = 0.91). The incidence of in-hospital myocardial infarction events was lower in the liberal transfusion group than in the restricted transfusion group (3.2% vs. 6.2%) (OR = 0.51, P = 0.048). The remaining in-hospital endpoint events, except for myocardial infarction, were not significantly different between the two groups. The 30-day and 60-day endpoints of death and inability to walk independently were not significantly different between the two groups, with ORs (95% CI) of 1.00 (0.75-1.31) and 1.06 (0.80-1.41), respectively. We also found no interaction between transfusion strategies and factors such as age, sex, or multiple underlying comorbidities at the 60-day follow-up. CONCLUSIONS: There was no significant difference in the in-hospital, 30-day or 60-day outcome endpoints between the two groups. However, this study demonstrated that a liberal transfusion strategy tends to reduce the incidence of in-hospital myocardial infarction events in patients with coronary artery disease combined with hip surgery compared to a restrictive transfusion strategy. More high-quality studies should be designed to investigate the optimal transfusion threshold in patients with coronary artery disease treated without cardiac surgery.

The Management and Antithrombotic Strategies of Patients with Coronary Artery Disease and High Bleeding Risk.

PURPOSE OF REVIEW: In this review, we aim to summarize the current understanding of high bleeding risk (HBR) patients in coronary artery disease (CAD) and provide a comprehensive evaluation of the available antithrombotic strategies for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) procedures. RECENT FINDINGS: CAD is a major cause of mortality among cardiovascular diseases, resulting from insufficient blood flow in the coronary artery due to atherosclerosis. Antithrombotic therapy is a crucial component of drug therapy for CAD and multiple studies had been focusing on the optimal antithrombotic strategies of different CAD populations. However, there is no fully harmonized definition of the model of bleeding, and the optimal antithrombotic strategy for such patients at HBR is inconclusive. In this review, we summarize bleeding risk stratification models for CAD patients and discuss the de-escalation of antithrombotic strategies among HBR patients. Furthermore, we realize that for certain subgroups of CAD-HBR patients, more individualized and precise antithrombotic strategy development is needed. So, we highlight special populations, such as CAD patients combined with valvular diseases, with both high ischemia and bleeding risks, and those proceeding surgical treatment, which requires greater research attention. We note that de-escalating therapy for CAD-HBR patients is an emerging trend in managing this population, but the optimal antithrombotic strategies should be re-considered according to the patient's baseline characteristics.

Glutathione inhibited starch digestion: Structural and kinetic analysis of substrate and α-amylase.

Glutathione (GSH) is a natural antioxidant that helps fight free radicals. Whether it will affect the activity of amylase and starch digestion remains unknown. This research disclosed that GSH could interact with starch through hydrogen bonds, which accelerated the swelling of starch granules and promoted the formation of ordered double-helix crystalline, and therefore inhibited starch digestion. Moreover, pig pancreas α-amylase (PPA) which was incubated with GSH displayed a less stable conformation and decreased activity. However, in a crowded media constructed by sodium caseinate (NaCas), an antagonistic effect existed between GSH and NaCas. As the rate and extent of starch digestion have been linked with health aspects, this study suggests that GSH can be used in the formulation of diet foods. It also reminds us to consider the synergistic or antagonistic effects caused by the coexisted components in the complexed food matrix.

Soluble ST2 in coronary artery disease: Clinical biomarkers and treatment guidance.

The IL-33/ST2 L signaling pathway is involved in the pathophysiological processes of several diseases and mainly exerts anti-inflammatory and antifibrotic effects. Soluble suppression of tumorigenicity 2 (sST2), which serves as a competitive inhibitory molecule of this pathway, is a member of the interleukin (IL)-1 family, a decoy receptor for IL33, thought to play a role in cardiac remodeling and the inflammatory process. However, the association between sST2 and coronary artery disease (CAD), one of the most common causes of heart failure, is still being explored. We therefore reviewed the research on sST2 in the field of CAD, including reflecting the atherosclerosis burden, predicting no-reflow, predicting prognosis, responding to myocardial remodeling, and guiding management, hoping to provide cardiologists with new perspectives.

An artificial intelligence-based risk prediction model of myocardial infarction.

BACKGROUND: Myocardial infarction can lead to malignant arrhythmia, heart failure, and sudden death. Clinical studies have shown that early identification of and timely intervention for acute MI can significantly reduce mortality. The traditional MI risk assessment models are subjective, and the data that go into them are difficult to obtain. Generally, the assessment is only conducted among high-risk patient groups. OBJECTIVE: To construct an artificial intelligence-based risk prediction model of myocardial infarction (MI) for continuous and active monitoring of inpatients, especially those in noncardiovascular departments, and early warning of MI. METHODS: The imbalanced data contain 59 features, which were constructed into a specific dataset through proportional division, upsampling, downsampling, easy ensemble, and w-easy ensemble. Then, the dataset was traversed using supervised machine learning, with recursive feature elimination as the top-layer algorithm and random forest, gradient boosting decision tree (GBDT), logistic regression, and support vector machine as the bottom-layer algorithms, to select the best model out of many through a variety of evaluation indices. RESULTS: GBDT was the best bottom-layer algorithm, and downsampling was the best dataset construction method. In the validation set, the F1 score and accuracy of the 24-feature downsampling GBDT model were both 0.84. In the test set, the F1 score and accuracy of the 24-feature downsampling GBDT model were both 0.83, and the area under the curve was 0.91. CONCLUSION: Compared with traditional models, artificial intelligence-based machine learning models have better accuracy and real-time performance and can reduce the occurrence of in-hospital MI from a data-driven perspective, thereby increasing the cure rate of patients and improving their prognosis.

Impact of Thrombocytopenia on In-Hospital Outcome in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI. METHODS: Using the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100 × 109/L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group (≤85 × 109/L), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion. RESULTS: Of 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p = 0.029). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding (BARC ≥ 2) (OR 2.56, 95% CI 1.24 to 5.44, p = 0.011). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p = 0.025). CONCLUSIONS: It seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.

Concomitant coronary and pulmonary embolism associated with patent foramen ovale: A case report.

RATIONALE: The differential diagnosis of acute chest pain is very important, and can sometimes be challenging. Related diseases share a number of risk factors, and occasionally, 1 condition causes another disease to develop. PATIENT CONCERNS: We described a 59-year-old man who presented to emergency department complaining of chest pain. DIAGNOSES: He was suffered acute myocardial infarction (MI) and pulmonary embolism (PE) simultaneously. INTERVENTIONS: Dual antiplatelet therapy, statin, and low molecular weight heparin were administrated during his stay. The searches for cancers, autoimmune diseases, and hematologic diseases were unremarkable, ruling out a hypercoagulable state. Subsequent ultrasound scan revealed a thrombus in a vein of the lower left extremity. Thus, paradoxical embolism was highly suspected. OUTCOMES: Paradoxical embolism is a rare cause of acute MI, which may have occurred in our patient. This was evidenced by a previously unrecognized patent foramen ovale (PFO) with a right-to-left atrial shunt detected using contrast transesophageal echocardiography. LESSONS: Acute MI complicated with PE is not common in the clinical setting. The fatal condition is difficult to diagnose because of the similar symptoms and confusing causes. Paradoxical embolism can cause this phenomenon, and physicians should be highly vigilant in the search for a PFO in cases of paradoxical embolism.

Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

AIMS: Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. METHODS AND RESULTS: In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. CONCLUSIONS: Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

Micellization and synergistic interaction of binary surfactant mixtures based on sodium nonylphenol polyoxyethylene ether sulfate.

Mixed micelle formation and synergistic interactions of binary surfactant combinations of sodium nonylphenol polyoxyethylene ether sulfate (NPES) with typical surfactants such as sodium dodecyl sulfate (SDS), Triton X-100 (TX100), cetyl trimethyl ammonium bromide (CTAB), and sodium bis(2-ethylhexyl) sulfosuccinate (AOT) at 25 degrees C in the presence of NaCl have been investigated. The critical micelle concentration of the binary mixtures has been quantitatively estimated by steady-state fluorescence measurements. The micellar characteristics such as composition, activity coefficients, and mutual interaction parameters have been estimated following different theoretical treatments. Investigation on the micellization and synergistic interaction of NPES with four kinds of surfactants showed that the behavior of the binary mixture deviated from the ideal state. The analysis revealed that the interaction parameter values (beta) varied with variation of solvent composition. Besides the strong electrostatic attraction between the oppositely charged surfactant NPES-CTAB mixture, the interaction between NPES and SDS also showed far more deviation from ideal behavior than that of TX100 and AOT. The reason for the synergism is also discussed and the results show that an ionic and a nonionic surfactant character existed concurrently in NPES due to the combination of a sulfate group and polyoxyethylene as a hydrophilic moiety. Zeta potential and diffusion coefficient measurements of micelles confirmed the synergistic interaction between the binary surfactants.