• 文章类型: Journal Article
    急性肾损伤(AKI)是最常见和严重的临床肾脏综合征之一,具有较高的发病率和病死率。Ferroptosis是程序性细胞死亡(PCD)的一种形式,以铁过载为特征,活性氧积累,和脂质过氧化。随着近年来对铁死亡的研究越来越多,与AKI的病理生理过程密切相关,为AKI的治疗提供了靶点。这篇综述提供了铁死亡的调节机制的全面概述,总结了它在各种AKI模型中的作用,并探索其与其他形式的细胞死亡的相互作用,它还介绍了AKI向其他疾病进展中的铁死亡的研究。此外,这篇综述重点介绍了通过铁凋亡透镜检测和评估AKI的方法,并描述了铁凋亡治疗AKI的潜在抑制剂.最后,这篇综述提出了对临床AKI治疗未来的看法,旨在刺激对AKI中铁蛋白的进一步研究。
    Acute kidney injury (AKI) is one of the most common and severe clinical renal syndromes with high morbidity and mortality. Ferroptosis is a form of programmed cell death (PCD), is characterized by iron overload, reactive oxygen species accumulation, and lipid peroxidation. As ferroptosis has been increasingly studied in recent years, it is closely associated with the pathophysiological process of AKI and provides a target for the treatment of AKI. This review offers a comprehensive overview of the regulatory mechanisms of ferroptosis, summarizes its role in various AKI models, and explores its interaction with other forms of cell death, it also presents research on ferroptosis in AKI progression to other diseases. Additionally, the review highlights methods for detecting and assessing AKI through the lens of ferroptosis and describes potential inhibitors of ferroptosis for AKI treatment. Finally, the review presents a perspective on the future of clinical AKI treatment, aiming to stimulate further research on ferroptosis in AKI.
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  • 文章类型: Journal Article
    前列腺癌(PCa)是美国男性中最常见的癌症,也是癌症相关死亡的主要原因。溶质载体家族14成员1(SLC14A1)是尿素转运蛋白的成员,对调节尿液浓度很重要。然而,SLC14A1在PCa中的生理意义仍不清楚。在本研究中,通过生物信息学分析和实验,我们发现SLC14A1的表达在PCa进展中显著降低,这可能归因于SLC14A1启动子区域的过度甲基化。此外,SLC14A1启动子的低表达和高甲基化与PCa患者的不良预后密切相关。另一方面,SLC14A1过表达抑制细胞增殖和转移,同时也抑制CDK1/CCNB1通路和mTOR/MMP-9信号通路。此外,SLC14A1表达在前列腺基底型细胞中富集。总之,我们的研究表明,SLC14A1的低表达水平和启动子甲基化可能是PCa进展和预后的新指标,SLC14A1可抑制PCa的进展。
    Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.
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  • 文章类型: Journal Article
    前列腺癌是男性中最常见和最致命的疾病之一,且其早期诊断可对治疗过程产生重大影响,预防死亡。由于它在早期没有明显的临床症状,很难诊断。此外,专家在分析磁共振图像方面的分歧也是一个重大挑战。近年来,各种研究表明,深度学习,尤其是卷积神经网络,已经成功地出现在机器视觉中(特别是在医学图像分析中)。在这项研究中,在多参数磁共振图像上使用了一种深度学习方法,研究了临床和病理数据对模型准确性的协同作用。数据是从德黑兰的Trita医院收集的,其中包括343例患者(在该过程中使用了数据增强和学习迁移方法).在设计的模型中,使用四个独立的ResNet50深度卷积网络分析了四种不同类型的图像,并将其提取的特征转移到完全连接的神经网络,并与临床和病理特征相结合。在没有临床和病理数据的模型中,最高准确率达到88%,但是通过添加这些数据,准确度提高到96%,临床和病理资料对诊断的准确性有显著影响。
    Prostate cancer is one of the most common and fatal diseases among men, and its early diagnosis can have a significant impact on the treatment process and prevent mortality. Since it does not have apparent clinical symptoms in the early stages, it is difficult to diagnose. In addition, the disagreement of experts in the analysis of magnetic resonance images is also a significant challenge. In recent years, various research has shown that deep learning, especially convolutional neural networks, has appeared successfully in machine vision (especially in medical image analysis). In this research, a deep learning approach was used on multi-parameter magnetic resonance images, and the synergistic effect of clinical and pathological data on the accuracy of the model was investigated. The data were collected from Trita Hospital in Tehran, which included 343 patients (data augmentation and learning transfer methods were used during the process). In the designed model, four different types of images are analyzed with four separate ResNet50 deep convolutional networks, and their extracted features are transferred to a fully connected neural network and combined with clinical and pathological features. In the model without clinical and pathological data, the maximum accuracy reached 88%, but by adding these data, the accuracy increased to 96%, which shows the significant impact of clinical and pathological data on the accuracy of diagnosis.
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  • 文章类型: Journal Article
    目的:探讨静脉-动脉体外膜氧合(VA-ECMO)支持下成人急性肾损伤(AKI)3期的发生率及危险因素。
    方法:回顾性病例对照研究。
    方法:单中心,阜外医院。
    方法:纳入2020年1月至2022年12月接受治疗的年龄≥18岁及以上的成人VA-ECMO患者。
    方法:根据患者是否发展为AKI肾病:改善总体预后(KDIGO)3期或<3期进行分组。采用多因素logistic回归分析评估AKI3期的危险因素。
    结果:在登记的患者中,40人(53.3%)发展为AKI3期。AKI3期患者的住院死亡率明显高于AKI<3期患者(67.5%vs34.3%;p=0.004)。多因素logistic回归分析显示,合并高血压(比值比[OR],0.250;95%置信区间[CI],0.063,0.987),p=0.048),ECMO前血红蛋白(或,0.969;95%CI,0.947-0.992;p=0.009),ECMO前乳酸(OR,1.173;95%CI,1.028-1.339;p=0.018),和ECMO前肌酐(OR,1.014;95%CI,1.003-1.025;p=0.011)是AKI3期的独立危险因素。
    结论:这项研究发现,在接受VA-ECMO支持的成年患者中,AKI3期的发生率很高(53.3%),并且与住院死亡率增加有关。合并高血压,低ECMO前血红蛋白,在接受VA-ECMO的患者中,ECMO前乳酸和ECMO前肌酐升高是AKI3期的独立危险因素.必须识别和调整这些风险因素,以增强VA-ECMO支持的结果。
    OBJECTIVE: To investigate the incidence and risk factors of acute kidney injury (AKI) stage 3 in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support.
    METHODS: A retrospective case-control study.
    METHODS: Single center, Fuwai Hospital.
    METHODS: Adult VA-ECMO patients age ≥18 years and older treated between January 2020 and December 2022 were included.
    METHODS: The patients were grouped by whether they developed AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 or <3. Multivariate logistic regression was performed t\"o evaluate risk factors of AKI stage 3.
    RESULTS: Among enrolled patients, 40 (53.3%) developed AKI stage 3. The in-hospital mortality of AKI stage 3 patients was significantly higher than that of AKI stage <3 patients (67.5% vs 34.3%; p = 0.004). Multivariate logistic regression analysis revealed that concomitant hypertension (odds ratio [OR], 0.250; 95% confidence interval [CI], 0.063, 0.987), p = 0.048), pre-ECMO hemoglobin (OR, 0.969; 95% CI, 0.947-0.992; p = 0.009), pre-ECMO lactate (OR, 1.173; 95% CI, 1.028-1.339; p = 0.018), and pre-ECMO creatinine (OR, 1.014; 95% CI, 1.003-1.025; p = 0.011) were independent risk factors for AKI stage 3.
    CONCLUSIONS: This study found a high incidence (53.3%) of AKI stage 3 in adult patients with VA-ECMO support and an association with increased in-hospital mortality. Concomitant hypertension, low pre-ECMO hemoglobin, and elevated pre-ECMO lactate and pre-ECMO creatinine were independent risk factors for AKI stage 3 in patients receiving VA-ECMO. It is imperative to identify and adjust these risk factors to enhance outcomes for those supported by VA-ECMO.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    目的:本研究旨在评估低对比剂的诊断功效和安全性,肾功能受损患者经导管主动脉瓣置换术(TAVR)前的双源双能量CT。
    方法:共54例连续患者(女性:男性,26:38;81.9±7.3年)肾功能降低的患者在2022年6月至2023年3月之间接受了30mL造影剂的TAVR前双能量CT。重建并分析了单色(40-和50-keV)和常规(120-kVp)图像。主观质量评分,血管衰减,对比噪声比(CNR),使用弗里德曼检验和事后分析在成像技术之间比较了信噪比(SNR)。使用组内相关系数(ICC)和Bland-Altman分析评估了主动脉瓣环测量的观察者间可靠性。评估对比后急性肾损伤(AKI)的手术结果和发生率。
    结果:单色图像在所有患者中均达到诊断质量。与常规CT相比,50keV图像实现了出色的血管衰减和CNR(全部P<0.001),同时保持了相似的SNR。对于主动脉瓣环测量,与传统CT相比,50keV图像显示出更高的观察者间可靠性:ICC,0.98vs.面积为0.90,面积为0.97vs.0.95周长;协议宽度的95%限制,0.63cm²vs.0.92cm²面积和5.78mmvs.周长8.50毫米。植入装置的大小与所有患者的CT测量值一致,达到92.6%的程序成功率。在CT后48-72小时内,没有患者的血清肌酐升高≥基线的1.5倍。然而,1例患者因肾功能逐渐恶化导致手术延迟.
    结论:采用50keV重建的低对比剂量成像能够实现精确的TAVR前评估,同时改善图像质量和最小化对比后AKI风险。这种方法可能是肾功能受损患者TAVR前评估的有效且安全的选择。
    OBJECTIVE: This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function.
    METHODS: A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed.
    RESULTS: Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR (P < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration.
    CONCLUSIONS: Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.
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  • 文章类型: Journal Article
    BACKGROUND: The worldwide prevalence of arterial hypertension in pediatric patients is 3.5%, and it has repercussions at renal, cardiovascular, neurological, and lifestyle levels. This study aimed to estimate the prevalence of arterial hypertension, mortality, and follow-up in patients with acute renal failure in the nephrology outpatient clinic at a second-level hospital in Northwestern Mexico.
    METHODS: We conducted a descriptive, retrospective, and observational study. Men and women aged 1-18 years diagnosed with acute kidney injury were analyzed from January 1, 2012, to December 31, 2021. The medical and electronic records of the candidate patients were analyzed, and nutritional data, laboratory analysis, most frequent etiology, and follow-up in the pediatric nephrology clinic were collected. Those with exacerbated chronic kidney disease and previous diagnosis of high blood pressure were excluded.
    RESULTS: One hundred and seventy-four patients were evaluated, and only 40 were eligible for the study (22.98%), predominantly males with a mean age of 9.9 years. The degree of arterial hypertension was 50% for grade I and 50% for grade II (p = 0.007); the mortality rate was 32%. One hundred percent of hypertension cases were controlled at 6 months after discharge (p = 0.000080).
    CONCLUSIONS: Our results were similar to those reported in other studies. Follow-up and early detection of arterial hypertension in children need to be strengthened.
    UNASSIGNED: La prevalencia de hipertensión arterial a nivel mundial es 3.5% en los pacientes pediátricos y tiene repercusiones tanto a nivel renal, cardiovascular, neurológico y estilo de vida. El objetivo de este estudio fue estimar la prevalencia de hipertensión arterial en pacientes con insuficiencia renal aguda, estimar la mortalidad y el seguimiento de los pacientes en la consulta externa de nefrología en un hospital de segundo nivel en el Noroeste de México.
    UNASSIGNED: Estudio observacional descriptivo, retrospectivo. Se analizaron hombres y mujeres entre 1 a 18 años de edad con el diagnóstico de lesión renal aguda, entre 1 de enero del 2012 hasta 31 de diciembre del 2021. Se analizaron las historias clínicas y el expediente electrónico de los pacientes candidatos, se recolectaron datos nutricionales, análisis de laboratorio, etiología más frecuente y el seguimiento en la consulta de nefrología pediátrica. Se excluyeron aquellos con enfermedad renal crónica agudizada y diagnóstico previo de hipertensión arterial.
    RESULTS: 174 pacientes fueron evaluados y solamente 40 fueron candidatos al estudio (22.98%), de los cuales predominaron masculinos con una edad media de 9.9 años. El grado de hipertensión arterial fue 50% para grado I y 50% para grado II (p = 0.007); tasa de mortalidad 32%. El 100% del control de la hipertensión se logró en el seguimiento del egreso de los pacientes en 6 meses (p = 0.000080).
    CONCLUSIONS: Nuestros resultados fueron similares a los reportados en otros estudios. Se debe reforzar el seguimiento y detección oportuna de hipertensión arterial en los niños.
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  • 文章类型: Journal Article
    背景:通过筛选和教育(CHANGE)计划的癌症健康意识提供了癌症意识教育,重点是可改变的危险因素和导航到前列腺筛查,乳房,和结肠直肠癌对公共住房社区的居民来说,他们经历了显著的负面健康社会决定因素。
    方法:五个社区的居民参与。招募社区顾问委员会成员,并向当地环境变化项目提供反馈,招募,以及每个站点的社区参与。在每个站点,由训练有素的主持人提供了四次关于癌症风险因素和病因的教育课程,种族差异,癌症筛查的资格,参与临床试验。出席,知识,对癌症的态度和信念,和高度,体重,在基线和更改后1周测量腰围.
    结果:90名居民(60%65岁及以上,33%男性,60%高中教育,93%AA)参加了该计划。95%完成干预后评估。参与者有资格获得乳房(n=12),前列腺(n=15),和结肠直肠筛查(n=25)基于美国癌症协会指南,和22个戒烟;21个参与者接受了这些服务的导航援助。在测试后,参与者对肥胖/超重癌症风险的知识和行为显着增加,营养,和身体活动。结肠直肠,前列腺,乳腺癌知识得分也有所提高,但并不重要。
    结论:CHANGE参与者表现出改善的健康知识和改善其可改变的健康行为的意图。参与者报告说,他们对寻求预防性护理和对社区参与工作的满意度有积极性和信心。在类似社区中复制该项目可能会改善服务不足人群的知识和健康公平性。
    BACKGROUND: The Cancer Health Awareness through screeNinG and Education (CHANGE) initiative delivers cancer awareness education with an emphasis on modifiable risk factors and navigation to screening for prostate, breast, and colorectal cancers to residents of public housing communities who experience significant negative social determinants of health.
    METHODS: Residents of five communities participated. Community advisory board members were recruited and provided feedback to local environmental change projects, recruitment, and community engagement at each site. At each site, four education sessions were provided by trained facilitators on cancer risk factors and etiology, racial disparities, eligibility for cancer screening, and participation in clinical trials. Attendance, knowledge, attitudes and beliefs about cancer, and height, weight, and waist circumference were measured at baseline and 1-week post-CHANGE sessions.
    RESULTS: 90 residents (60% 65 and older years old, 33% male, 60% High School education, 93% AA) participated in the program. 95% completed post-intervention evaluation. Participants were eligible for breast (n = 12), prostate (n = 15), and colorectal screening (n = 25) based on American Cancer Society guidelines, and 22 for tobacco cessation; 21 participants accepted navigation assistance for these services. At post-test, participants significantly increased in knowledge and behaviors around obesity/overweight risk for cancer, nutrition, and physical activity. Colorectal, prostate, and breast cancer knowledge scores also increased, but were not significant.
    CONCLUSIONS: CHANGE participants demonstrated improved health knowledge and intentions to improve their modifiable health behaviors. Participants reported being motivated and confident in seeking preventive care and satisfaction with community engagement efforts. Replication of this project in similar communities may improve knowledge and health equity among underserved populations.
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  • 文章类型: Journal Article
    建议采用基于曲线下面积(AUC24)的方法来指导万古霉素治疗药物监测(TDM),尽管存在相关风险,但仍普遍使用谷浓度。缺乏明确的毒性目标,这对于肾毒性风险较高的血液学患者很重要。目的是(1)评估基于波谷的TDM对急性肾损伤(AKI)发生率的影响,(2)树立万古霉素肾毒性阈值,(3)评估血液学患者达到万古霉素治疗目标的比例。回顾性数据收集了2020年4月至2021年1月期间接受万古霉素治疗的100名患有血液系统恶性肿瘤或再生障碍性贫血的成年患者。AKI的发生是根据血清肌酐浓度确定的,和个体药代动力学参数使用贝叶斯方法估计。进行受试者工作特征(ROC)曲线分析以评估药代动力学指标预测AKI发生的能力。基于AUC24/MIC≥400和确定的毒性阈值评估达到目标万古霉素暴露的患者比例。AKI发生率为37%。ROC曲线分析表明最大AUC24为644mg。治疗期间的h/L是AKI的重要预测因子。到治疗的第4天,29%的疗程有治疗性万古霉素暴露,只有62%的课程达到AUC24目标。鉴定的毒性阈值支持400-650mg的AUC24目标范围。h/L,假设MIC为1毫克/升,以优化万古霉素的疗效和减少毒性。这项研究强调了该人群中AKI的高发生率,并强调了从基于波谷的TDM过渡到基于AUC的方法以改善临床结果的重要性。
    An area-under-the-curve (AUC24)-based approach is recommended to guide vancomycin therapeutic drug monitoring (TDM), yet trough concentrations are still commonly used despite associated risks. A definitive toxicity target is lacking, which is important for hematology patients who have a higher risk of nephrotoxicity. The aims were to (1) assess the impact of trough-based TDM on acute kidney injury (AKI) incidence, (2) establish a vancomycin nephrotoxicity threshold, and (3) evaluate the proportion of hematology patients achieving vancomycin therapeutic targets. Retrospective data was collected from 100 adult patients with a hematological malignancy or aplastic anemia who received vancomycin between April 2020 and January 2021. AKI occurrence was determined based on serum creatinine concentrations, and individual pharmacokinetic parameters were estimated using a Bayesian approach. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pharmacokinetic indices to predict AKI occurrence. The proportion of patients who achieved target vancomycin exposure was evaluated based on an AUC24/MIC ≥400 and the determined toxicity threshold. The incidence of AKI was 37%. ROC curve analysis indicated a maximum AUC24 of 644 mg.h/L over the treatment period was an important predictor of AKI. By Day 4 of treatment, 29% of treatment courses had supratherapeutic vancomycin exposure, with only 62% of courses achieving AUC24 targets. The identified toxicity threshold supports an AUC24 target range of 400-650 mg.h/L, assuming an MIC of 1 mg/L, to optimize vancomycin efficacy and minimize toxicity. This study highlights high rates of AKI in this population and emphasizes the importance of transitioning from trough-based TDM to an AUC-based approach to improve clinical outcomes.
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  • 文章类型: Journal Article
    背景:急性肾损伤(AKI)是一种影响大部分危重患者的综合征,早期诊断以接受适当的治疗是必要的,因为早期诊断具有挑战性。因此,已经开发了机器学习方法来提前预测AKI。然而,在最先进的方法中,AKI的患病率往往被低估,因为它们依赖于仅基于肌酐的AKI事件注释,忽略尿量。
    我们在多学科的ICU环境中构建和评估AKI的预警系统,使用AKI的完整KDIGO定义。我们提出了基于梯度提升决策树(GBDT)的模型的几种变体,包括一种新颖的基于时间堆叠的方法。使用先前提出的用于AKI预测的基于LSTM的最先进模型作为比较,尚未在ICU设置中进行专门评估。
    结果:我们发现,通过使用GBDT与基于时间的堆叠技术(AUPRC=65.7%,与基于LSTM的模型的AUPRC=62.6%相比),这是由于自ICU入院以来时间的高度相关性。这两个模型在有限的训练数据设置中都显示出轻微的性能下降,在不同的子队列中表现公平,在性别转移方面没有问题。
    遵循官方的KDIGO定义大大增加了带注释的AKI事件的数量。在我们的研究中,GBDT在AKI预测方面优于LSTM模型。一般来说,我们发现两种模型类型在ICU数据出现的各种具有挑战性的设置中都是稳健的.
    方法:复制我们手稿发现的代码可以在以下网址找到:https://github.com/ratschlab/AKI-EWS。
    BACKGROUND: Acute kidney injury (AKI) is a syndrome that affects a large fraction of all critically ill patients, and early diagnosis to receive adequate treatment is as imperative as it is challenging to make early. Consequently, machine learning approaches have been developed to predict AKI ahead of time. However, the prevalence of AKI is often underestimated in state-of-the-art approaches, as they rely on an AKI event annotation solely based on creatinine, ignoring urine output.
    We construct and evaluate early warning systems for AKI in a multi-disciplinary ICU setting, using the complete KDIGO definition of AKI. We propose several variants of gradient-boosted decision tree (GBDT)-based models, including a novel time-stacking based approach. A state-of-the-art LSTM-based model previously proposed for AKI prediction is used as a comparison, which was not specifically evaluated in ICU settings yet.
    RESULTS: We find that optimal performance is achieved by using GBDT with the time-based stacking technique (AUPRC = 65.7%, compared with the LSTM-based model\'s AUPRC = 62.6%), which is motivated by the high relevance of time since ICU admission for this task. Both models show mildly reduced performance in the limited training data setting, perform fairly across different subcohorts, and exhibit no issues in gender transfer.
    Following the official KDIGO definition substantially increases the number of annotated AKI events. In our study GBDTs outperform LSTM models for AKI prediction. Generally, we find that both model types are robust in a variety of challenging settings arising for ICU data.
    METHODS: The code to reproduce the findings of our manuscript can be found at: https://github.com/ratschlab/AKI-EWS.
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