Driving pressure association with mortality in post-lung transplant patients: A prospective observational study.

OBJECTIVE: To investigate the association between driving pressure (ΔP) and 90-day mortality in patients following lung transplantation (LTx) in patients who developed primary graft dysfunction (PGD). METHODS: This prospective, observational study involved consecutive patients who, following LTx, were admitted to our intensive care unit (ICU) from January 2022 to January 2023. Patients were separated into two groups according to ΔP at time of admission (i.e., low, ≤15 cmH2O or high, >15 cmH2O). Postoperative outcomes were compared between groups. RESULTS: In total, 104 patients were involved in the study, and of these, 69 were included in the low ΔP group and 35 in the high ΔP group. Kaplan-Meier analysis of 90-day mortality showed a statistically significant difference between groups with survival better in the low ΔP group compared with the high ΔP group. According to Cox proportional regression model, the variables independently associated with 90-day mortality were ΔP and pneumonia. Significantly more patients in the high ΔP group than the low ΔP group had PGD grade 3 (PGD3), pneumonia, required tracheostomy, and had prolonged postoperative extracorporeal membrane oxygenation (ECMO) time, postoperative ventilator time, and ICU stay. CONCLUSIONS: Driving pressure appears to have the ability to predict PGD3 and 90-day mortality of patients following LTx. Further studies are required to confirm our results.

A novel nomogram for predicting prolonged mechanical ventilation in lung transplantation patients using extracorporeal membrane oxygenation.

Prolonged mechanical ventilation (PMV) is commonly associated with increased post-operative complications and mortality. Nevertheless, the predictive factors of PMV after lung transplantation (LTx) using extracorporeal membrane oxygenation (ECMO) as a bridge remain unclear. The present study aimed to develop a novel nomogram for PMV prediction in patients using ECMO as a bridge to LTx. A total of 173 patients who used ECMO as a bridge following LTx from January 2022 to June 2023 were divided into the training (122) and validation sets (52). A mechanical ventilation density plot of patients after LTx was then performed. The training set was divided in two groups, namely PMV (95) and non-prolonged ventilation (NPMV) (27). For the survival analysis, the effect of PMV was assessed using the log-rank test. Univariate and multivariate logistic regression analyses were performed to assess factors associated with PMV. A risk nomogram was established based on the multivariate analysis, and model performance was further assessed in terms of calibration, discrimination, and clinical usefulness. Internal validation was additionally conducted. The difference in survival curves in PMV and NPMV groups was statistically significant (P < 0.001). The multivariate analysis and risk factors in the nomogram revealed four factors to be significantly associated with PMV, namely the body mass index (BMI), operation time, lactic acid at T0 (Lac), and driving pressure (DP) at T0. These four factors were used to develop a nomogram, with an area under the curve (AUC) of 0.852 and good calibration. After internal validation, AUC was 0.789 with good calibration. Furthermore, goodness-of-fit test and decision-curve analysis (DCA) indicated satisfactory performance in the training and internal validation sets. The proposed nomogram can reliably and accurately predict the risk of patients to develop PMV after LTx using ECMO as a bridge. Four modifiable factors including BMI, operation time, Lac, and DP were optimized, which may guide preventative measures and improve prognosis.

Combination of platelet-to-lymphocyte ratio and D-dimer for the identification of cardiogenic cerebral embolism in non-valvular atrial fibrillation.

Background: Non-valvular atrial fibrillation (NVAF) is the most common cause of cardiogenic cerebral embolism (CCE). However, the underlying mechanism between cerebral embolism and NVAF is indefinite, and there is no effective and convenient biomarker to identify potential risk of CCE in patients with NVAF in clinic. The present study aims to identify risk factors for interpreting the potential association of CCE with NVAF and providing valuable biomarkers to predict the risk of CCE for NVAF patients. Methods: 641 NVAF patients diagnosed with CCE and 284 NVAF patients without any history of stroke were recruited in the present study. Clinical data including demographic characteristics, medical history, and clinical assessments, were recorded. Meanwhile, Blood cell counts, lipid profiles, high-sensitivity C-reactive protein, and coagulation function-related indicators were measured. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a composite indicator model based on the blood risk factors. Results: (1) CCE patients had significantly increased neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and D-dimer levels as compared with patients in the NVAF group, and these three indicators can distinguish CCE patients from ones in the NVAF group with an area under the curve (AUC) value of over 0.750, respectively. (2) Using the LASSO model, a composite indicator, i.e., the risk score, was determined based on PLR and D-dimer and displayed differential power for distinguishing CCE patients from NVAF patients with an AUC value of over 0.934. (3) The risk score was positively correlated with the National Institutes of Health Stroke Scale and CHADS2 scores in CCE patients. (4) There was a significant association between the change value of the risk score and the recurrence time of stroke in initial CCE patients. Conclusions: The PLR and D-dimer represent an aggravated process of inflammation and thrombosis in the occurrence of CCE after NVAF. The combination of these two risk factors can contribute to identifying the risk of CCE for patients with NVAF with an accuracy of 93.4%, and the greater in change of composite indicator, the shorter in the recurrence of CCE for NVAF patients.

Up-regulation of MMP-2 by histone H3K9 ß-hydroxybutyrylation to antagonize glomerulosclerosis in diabetic rat.

AIMS: Besides energy supply, ß-hydroxybutyrate (BHB) acts as a bioactive molecule to play multiple protective roles, even in diabetes and its complications. The aim of this study was to investigate the antagonizing effects of BHB against diabetic glomerulosclerosis and the underlying mechanism. METHODS: Male Sprague-Dawley rats were intraperitoneally injected with streptozotocin to induce diabetes and then treated with different concentrations of ß-hydroxybutyrate. After 10 weeks, body weight, blood glucose, serum creatinine and 24-h urine protein were examined. Glomerular morphological changes and the contents of collagen type IV (COL IV) were evaluated. Then, transforming growth factor (TGF)-ß/Smad3 contents and matrix metalloproteinase-2 (MMP-2) generation were detected. Moreover, the total contents of trans-activating histone H3K9 ß-hydroxybutyrylation (H3K9bhb) and the contents of H3K9bhb in the Mmp-2 promoter were measured. RESULTS: It was firstly confirmed that BHB treatments reduced renal biochemical indicators and attenuated glomerular morphological changes of the diabetic rats, with COL IV content decreased in a concentration-dependent manner. Then, BHB treatments were found to up-regulate renal MMP-2 generation of the diabetic rats significantly, while not affecting the increased TGF-ß/Smad3 contents. Furthermore, the contents of H3K9bhb in the Mmp-2 promoter were elevated significantly for the middle and high concentrations of BHB treatments, up-regulating MMP-2 generation. CONCLUSION: BHB treatments could up-regulate MMP-2 generation via causing elevated H3K9bhb in its promoter to antagonize glomerulosclerosis in the diabetic rats.