A Nomogram Model for Predicting Type-2 Myocardial Infarction Induced by Acute Upper Gastrointestinal Bleeding.

OBJECTIVE: To examine the independent risk factors of type-2 myocardial infarction (T2MI) elicited by acute upper gastrointestinal bleeding (AUGIB), and to establish a nomogram model for the prediction of AUGIB-induced T2MI. METHODS: A nomogram model was established on the basis of a retrospective study that involved 533 patients who suffered from AUGIB in the Department of Critical Care Medicine (CCM) or Emergency Intensive Care Unit (EICU) of Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to December 2020. The predictive accuracy and discriminative power of the nomogram were initially evaluated by internal validation, which involved drawing the receiver operating characteristic (ROC) curve, calculating the area under the curve (AUC), plotting the calibration curve derived from 1000 resampled bootstrap data sets, and computing the root mean square error (RMSE). The predictive ability of the nomogram was further validated through the prospective and multicenter study conducted by the investigators, which enrolled 240 AUGIB patients [including 88 cases from Renmin Hospital of Wuhan University, 73 cases from Qilu Hospital of Shandong University (Qingdao), and 79 cases from Northern Jiangsu People's Hospital)], who were admitted to the Department of CCM or EICU, from February 2021 to July 2021. RESULTS: Among the 533 patients in the training cohort, 78 (14.6%) patients were assigned to the T2MI group and 455 (85.4%) patients were assigned to the non-T2MI group. The multivariate analysis revealed that age >65, hemorrhagic shock, cerebral stroke, heart failure, chronic kidney disease, increased blood urea nitrogen, decreased hematocrit, and elevated D-Dimer were independent risk factors for AUGIB-induced T2MI. All these factors were incorporated into the nomogram model. The AUC for the nomogram for predicting T2MI was 0.829 (95% CI, 0.783-0.875) in the internal validation cohort and 0.848 (95% CI, 0.794-0.902) in the external validation cohort. The calibration curve for the risk of T2MI exhibited good consistency between the prediction by the nomogram and the actual clinical observation in both the internal validation (RMSE=0.016) and external validation (RMSE=0.020). CONCLUSION: The nomogram was proven to be a useful tool for the risk stratification of T2MI in AUGIB patients, and is helpful for the early identification of AUGIB patients who are prone to T2MI for early intervention, especially in emergency departments and intensive care units.

Mitochondrial Autophagy and NLRP3 Inflammasome in Pulmonary Tissues from Severe Combined Immunodeficient Mice after Cardiac Arrest and Cardiopulmonary Resuscitation.

BACKGROUND: The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury. METHODS: A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1. RESULTS: (1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P = 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser327) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t = -1.36, P < 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t = -0.33, P < 0.01), whereas phos-ULK1 (Ser757) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P < 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P < 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P = 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome. CONCLUSIONS: There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained.