AKI-Pro score for predicting progression to severe acute kidney injury or death in patients with early acute kidney injury after cardiac surgery.

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.

Postoperative glucocorticoids in patients with acute type A aortic dissection (GLAD): study protocol for a prospective, single-center, randomized controlled trial.

BACKGROUND: Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. METHODS: This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. DISCUSSION: The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

Early postoperative organ dysfunction is highly associated with the mortality risk of patients with type A aortic dissection.

OBJECTIVES: This study assessed the impact of early postoperative organ dysfunction (EPOD) on in-hospital mortality of patients with type A aortic dissection (TAAD) after surgery. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest from January 2020 to December 2021 were included. The Sequential Organ Failure Assessment (SOFA) score was calculated for 3 days postoperatively to stratify the severity of organ dysfunction. Patients with the SOFA of 0-4, 5-8 or >8 were defined as mild, moderate or severe EPOD. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Kaplan-Meier curves were used to compare survival probability. The area under the receiver operating characteristic curve and calibration plots were used to evaluate the predictive power and overall performance of SOFA. RESULTS: Of the 368 patients, 5 patients (3%) with moderate EPOD and 33 patients (23%) with severe EPOD died. No patient died with mild EPOD. The areas under the receiver operating characteristic curve of SOFA for predicting mortality and the composite outcome were 0.85 (0.81-0.88) and 0.81 (0.77-0.85) on postoperative day 1. Each point of postoperative day 1 SOFA score corresponded to an odds ratio of 1.65 (1.42-1.92) for mortality. Of the 6 components of the SOFA system, only coagulation (2.34 [1.32-4.13]), cardiovascular (1.47 [1.04-2.08]), central nervous system (1.96 [1.36-2.82]) and renal (1.67 [1.04-2.70]) functions were associated with the higher risk of mortality. CONCLUSIONS: EPOD stratified by the SOFA score was associated with a higher risk of death and predicted the clinical outcomes of patients with TAAD with good accuracy.

The role of prostate-specific antigen density and negative multiparametric magnetic resonance imaging in excluding prostate cancer for biopsy-naïve men: clinical outcomes from a high-volume center in China.

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.

Exosome-Derived From Sepsis Patients' Blood Promoted Pyroptosis of Cardiomyocytes by Regulating miR-885-5p/HMBOX1.

Background: Septic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood. Materials and Methods: Exosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1ß and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression. Results: Sepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1ß and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent. Conclusion: Sepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.

The comparison of survival between active surveillance or watchful waiting and focal laser ablation in patients with low-risk prostate cancer.

Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010-2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan-Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37-3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02-2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.

The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer: a real-world study from the SEER database.

To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02-1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23-4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92-1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24-6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury.

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%-15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.