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Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. This property depends on the active nuclear import of its intracellular reverse transcription complex (RTC). We have studied nuclear import of purified HIV-1 RTCs in primary macrophages and found that importin 7, an import receptor for ribosomal proteins and histone H1, is involved in the process. Nuclear import of RTCs requires, in addition, energy and the com ponents of the Ran system. Depletion of importin 7 from cultured cells by small interfering RNA inhibits HIV-1 infection. These results provide a new insight into the molecular mechanism for HIV-1 nuclear import and reveal potential targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

A significant number of patients develop chronic pain after surgery, but prediction of those who are at risk is currently not possible. Thus, prognostic prediction models that include bio-psycho-social and physiological factors in line with the complex nature of chronic pain would be urgently required. Here, we performed a translational study in male volunteers before and after an experimental incision injury. We determined multi-modal features ranging from pain characteristics and psychological questionnaires to blood plasma proteomics. Outcome measures included pain intensity ratings and the extent of the area of hyperalgesia to mechanical stimuli surrounding the incision, as a proxy of central sensitization. A multi-step logistic regression analysis was performed to predict outcome measures based on feature combinations using data-driven cross-validation and prognostic model development. Phenotype-based stratification resulted in the identification of low and high responders for both outcome measures. Regression analysis revealed prognostic proteomic, specific psychophysical, and psychological features. A combinatorial set of distinct features enabled us to predict outcome measures with increased accuracy compared to using single features. Remarkably, in high responders, protein network analysis suggested a protein signature characteristic of low-grade inflammation. Alongside, in silico drug repurposing highlighted potential treatment options employing antidiabetic and anti-inflammatory drugs. Taken together, we present here an integrated pipeline that harnesses bio-psycho-physiological data for prognostic prediction in a translational approach. This pipeline opens new avenues for clinical application with the goal of stratifying patients and identifying potential new targets, as well as mechanistic correlates, for postsurgical pain., Competing Interests: Declaration of Competing Interest MS received research awards and travel support by the German Pain Society (DGSS) both of which were sponsored by Astellas Pharma GmbH (Germany). MS received one-time consulting honoraria by Grunenthal GmbH (Germany). None of these funding sources influenced the content of this study, and MS declares no conflict of interest. During the past 3 yr, EPZ received financial support from Grunenthal for research activities and from Grunenthal (Germany), Medtronic and Merck/MSD for advisory board activities, lecture fees, or both. All money went to the institution EPZ is working for. None of this research support/funds was used for or influenced this manuscript, and EPZ declares no conflict of interest. The remaining authors declare that they have no conflicts of interest., (Copyright © 2025. Published by Elsevier Ltd.)

This study aims to improve our understanding of acute ischemic stroke clot imaging by integrating CT attenuation information with MRI susceptibility signal of thrombi. For this proof-of-principle experimental study, fifty-seven clot analogs were produced using ovine venous blood with a broad histological spectrum. Each clot analog was analyzed to determine its RBC content and chemical composition, including water, Fe III, sodium, pH, and pO2. Non-contrast CT and a susceptibility-weighted MRI sequence were used for imaging. The study found that RBC content correlated more accurately than iron content with clot attenuation on CT. There was a strong correlation between Fe III content and RBC percentage in clots. Specifically, changes in RBC content accounted for 64% of the variance in Fe III content (R2 = 0.640; p < .0001). Thrombi with blooming artifacts (BA) displayed higher attenuation on non-contrast CT than those without (73.4 vs. 40 HU, p < .0001) and had the highest RBC and iron contents. The cut-off value of 1242 µg/g of iron predicted blooming artifacts with high sensitivity and specificity. The pH level strongly affected the appearance of blooming artifacts, particularly for negative clots with high RBC content. These findings provide significant insights into the imaging behavior of acute ischemic stroke clots across both imaging modalities and could potentially improve the diagnosis and treatment of acute stroke patients. Furthermore, these results open the possibility for future research aimed at developing pH-modulated therapeutic strategies based on the acid-base state of thrombi., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Artificial intelligence promises to revolutionize mental health care, but small dataset sizes and lack of robust methods raise concerns about result generalizability. To provide insights on minimal necessary data set sizes, we explore domain-specific learning curves for digital intervention dropout predictions based on 3654 users from a single study (ISRCTN13716228, 26/02/2016). Prediction performance is analyzed based on dataset size (N = 100-3654), feature groups (F = 2-129), and algorithm choice (from Naive Bayes to Neural Networks). The results substantiate the concern that small datasets (N ≤ 300) overestimate predictive power. For uninformative feature groups, in-sample prediction performance was negatively correlated with dataset size. Sophisticated models overfitted in small datasets but maximized holdout test results in larger datasets. While N = 500 mitigated overfitting, performance did not converge until N = 750-1500. Consequently, we propose minimum dataset sizes of N = 500-1000. As such, this study offers an empirical reference for researchers designing or interpreting AI studies on Digital Mental Health Intervention data., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged <60 years with de novo AML classified as 2022 ELN favorable genetic risk who achieved a CR and had RNA sequencing (RNA-seq) and gene mutation data from diagnostic samples available (Alliance trial A152010). To identify prognostically relevant transcripts that can distinguish patients cured from patients susceptible to lower or higher risk of relapse or death, we fit a regularized mixture cure model (MCM) where RNA-seq expression values were our candidate covariates. To validate the identified transcripts, we analyzed 75 patients with de novo AML aged <60 years included in the 2022 ELN favorable genetic risk group who achieved a CR in an independent test set from Gene Expression Omnibus (GSE37642). Our MCM identified 145 transcripts associated with cure or long-term RFS and 149 transcripts associated with latency or shorter-term time to relapse. The area under the curve and C-statistic were, respectively, 0.946 and 0.856 for our training set and 0.877 and 0.857 for our test set. Our results suggest that the favorable risk group includes distinct transcriptionally defined subgroups with different biological properties, which may be useful for refining this genetic risk category., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Purpose: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers., Experimental Design: We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response and cytolytic effector functions in the tumor microenvironment. To allow stratification of patients according to tumor GD2 expression, we established and validated immunofluorescence detection of GD2 on paraffin-embedded tumor tissues., Results: Lentiviral all-in-one vector engineering of human T cells with the GD2-specific CAR with and without inducible IL18 resulted in cell products with comparable proportions of CAR-expressing central memory T cells. Production of IL18 strictly depends on GD2 antigen engagement. GD2IL18CART respond to interaction with GD2-positive tumor cells with higher IFNγ and TNFα cytokine release and more effective target cytolysis compared with CAR T cells without inducible IL18. GD2IL18CART further have superior in vivo antitumor activity, with eradication of GD2-positive tumor xenografts. Finally, we established GMP-compliant manufacturing of GD2IL18CART and found it to be feasible and efficient at clinical scale., Conclusions: These results pave the way for clinical investigation of GD2IL18CART in pediatric and adult patients with neuroblastoma and other GD2-positive cancers (EU CT 2022- 501725-21-00). See related commentary by Locatelli and Quintarelli, p. 3361., (©2024 American Association for Cancer Research.)

Purpose: Every year, approximately 10 million people worldwide suffer a traumatic brain injury that leads to hospitalization or mortality. Chronic and acute alcohol intoxication increase the risk of developing traumatic brain injury. Alcohol use disorder (AUD) as a predictor of outcome in neurosurgical patients and the definition of risk factors have been sparsely addressed so far. This study aims to improve the understanding of the effects of alcohol use disorder in the context of neurosurgical therapy., Methods: This study included patients admitted to Münster University Hospital with a traumatic brain injury and alcohol use disorder from January 1, 2010, to December 31, 2018. Univariate and multivariate analyses were performed to identify risk factors for a poorer outcome, assessed by the Glasgow Outcome Score., Results: Of the 197 patients included, 156 (79%) were male, and 41 (21%) were female, with a median age of 49 years (IQR 38-58 years). In multivariate analyses, age (p < 0.001), the occurrence of a new neurologic deficit (p < 0.001), the development of hydrocephalus (p = 0.005), and CT-graphic midline shift due to intracerebral hemorrhage (p = 0.008) emerged as significant predictors of a worse outcome (GOS 1-3). In addition, the level of blood alcohol concentration correlated significantly with the occurrence of seizures (p = 0.009)., Conclusions: Early identification of risk factors in patients with alcohol use disorder and traumatic brain injury is crucial to improve the outcome. In this regard, the occurrence of hydrocephalus or seizures during the inpatient stay should be considered as cause of neurological deterioration in this patient group., (© 2023. The Author(s).)

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor ( n = 276) and those who received a graft from a non-smoking donor ( n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Becker, Pollmann, Funke-Kaiser, Görlich, Katou, Morgül, Kneifel, Reuter, Pascher and Houben.)

Nuclear pore complex (NPC) biogenesis is a still enigmatic example of protein self-assembly. We now introduce several cross-reacting anti-Nup nanobodies for imaging intact nuclear pore complexes from frog to human. We also report a simplified assay that directly tracks postmitotic NPC assembly with added fluorophore-labeled anti-Nup nanobodies. During interphase, NPCs are inserted into a pre-existing nuclear envelope. Monitoring this process is challenging because newly assembled NPCs are indistinguishable from pre-existing ones. We overcame this problem by inserting Xenopus-derived NPCs into human nuclear envelopes and using frog-specific anti-Nup nanobodies for detection. We further asked whether anti-Nup nanobodies could serve as NPC assembly inhibitors. Using a selection strategy against conserved epitopes, we obtained anti-Nup93, Nup98, and Nup155 nanobodies that block Nup-Nup interfaces and arrest NPC assembly. We solved structures of nanobody-target complexes and identified roles for the Nup93 α-solenoid domain in recruiting Nup358 and the Nup214·88·62 complex, as well as for Nup155 and the Nup98 autoproteolytic domain in NPC scaffold assembly. The latter suggests a checkpoint linking pore formation to the assembly of the Nup98-dominated permeability barrier., (© 2024. The Author(s).)

Knowledge of thrombus behavior and visualization on MRI in acute ischemic stroke is less than optimal. However, MRI sequences could be enhanced based on the typical T1 and T2 relaxation times of the target tissues, which mainly determine their signal intensities on imaging. We studied the relaxation times of a broad spectrum of clot analogs along with their image characteristics of three sequences analyzed: a T1-weighted turbo inversion-recovery sequence (T1w Turbo IR), a T1-weighted turbo spin echo with fat suppression (T1w TSE SPIR), and a T2-weighted 3D TSE with magnetization refocusing to remove T1 dependence (T2w TSE DRIVE). We compared their imaging behavior with the intensity values of normal brain tissue using the same imaging protocols as for clots. Each histological and biochemical clot component contributed to each of the relaxation times. Overall, histological composition correlated strongly with T1 times, and iron content, specifically, with T2 relaxation time. Using decision trees, fibrin content was selected as the primary biomarker for T1 relaxation times, inducing an increase. Up to four clot subgroups could be defined based on its distinctive T1 relaxation time. Clot signal intensity in the T1 and T2-weighted images varied significantly according to T1 and T2 relaxation times. Moreover, in comparison with normal brain tissue intensity values, T2w DRIVE images depict thrombi according to the principle of the more fibrin, the higher the intensity, and in T1w TSE, the more erythrocytes, the higher the intensity. These findings could facilitate improvements in MRI sequences for clot visualization and indicate that T2w DRIVE and T1w TSE sequences should depict the vast majority of acute ischemic stroke thrombi as more hyperintense than surrounding tissues., (© 2024. The Author(s).)

Carbohydrate markers of immature cells during prenatal human development can be aberrantly expressed in cancers and deserve evaluation as immune targets. A candidate target in Ewing sarcoma is the globo-series ganglioside stage-specific embryonic antigen-4 (SSEA-4). We detected SSEA-4 expression on the cell surface of all of 14 EwS cell lines and in 21 of 31 (68%) primary EwS tumor biopsies. Among paired subpopulations of tumor cells with low versus high SSEA-4 expression, SSEA-4 high expression was significantly and consistently associated with functional characteristics of tumor aggressiveness, including higher cell proliferation, colony formation, chemoresistance and propensity to migrate. SSEA-4 low versus SSEA-4 high expression was not related to expression levels of the EWSR1-FLI1 fusion transcript or markers of epithelial/mesenchymal plasticity. SSEA-4 low cells selected from bulk populations regained higher SSEA-4 expression in vitro and during in vivo tumor growth in a murine xenograft model. T cells engineered to express SSEA-4-specific chimeric antigen receptors (CARs) specifically interacted with SSEA-4 positive EwS cells and exerted effective antigen-specific tumor cell lysis in vitro. In conclusion, with its stable expression and functional significance in EwS, SSEA-4 is an attractive therapeutic immune target in this cancer that deserves further evaluation for clinical translation., (© 2024. The Author(s).)

Background: We investigated differences in intracranial embolus distribution through communicating arteries in relation to supra-aortic vessel (SAV) patency., Methods: For this experimental analysis, we created a silicone model of the extracranial and intracranial circulations using a blood-mimicking fluid under physiological pulsatile flow. We examined the sequence of embolus lodgment on injecting 104 frangible clot analogues (406 emboli) through the right internal carotid artery (CA) as SAV patency changed: (a) all SAV patent (baseline), (b) emboli from a CA occlusion, (c) emboli contralateral to a CA occlusion and (d) occlusion of the posterior circulation. The statistical analysis included a descriptive analysis of thrombi location after occlusion (absolute and relative frequencies). Sequences of occlusions were displayed in Sankey flow charts for the four SAV conditions. Associations between SAV conditions and occlusion location were tested by Fisher's exact test. Two-sided p values were compared with a significance level of 0.05., Results: The total number of emboli was 406 (median fragments/clot: 4 (IQR: 3-5)). Embolus lodgment was dependent on SAV patency (p<0.0001). In all scenarios, embolism lodging in the anterior cerebral artery (ACA) occurred after a previous middle cerebral artery (MCA) embolism (MCA first lodge: 96%, 100/104). The rate of ipsilateral ACA embolism was 28.9% (28/97) at baseline, decreasing significantly when emboli originated from an occluded CA (16%, 14/88). There were more bihemispheric embolisations in cases of contralateral CA occlusion (37%, 45/122), with bilateral ACA embolisms preceding contralateral MCA embolism in 56% of cases (14/25 opposite MCA and ACA embolism)., Conclusions: All emboli in the ACA occurred after a previous ipsilateral MCA embolism. Bihemispheric embolisms were rare, except when there was a coexisting occlusion in either CA, particularly in cases of a contralateral CA occlusion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Resuscitation is a team effort, and it is increasingly acknowledged that team cooperation requires training. Staff shortages in many healthcare systems worldwide, as well as recent pandemic restrictions, limit opportunities for collaborative team training. To address this challenge, a learner-centred approach known as flipped learning has been successfully implemented. This model comprises self-directed, asynchronous pre-course learning, followed by knowledge application and skill training during in-class sessions. The existing evidence supports the effectiveness of this approach for the acquisition of cognitive skills, but it is uncertain whether the flipped classroom model is suitable for the acquisition of team skills. The objective of this study was to determine if a flipped classroom approach, with an online workshop prior to an instructor-led course could improve team performance and key resuscitation variables during classroom training., Methods: A single-centre, cluster-randomised, rater-blinded study was conducted on 114 final year medical students at a University Hospital in Germany. The study randomly assigned students to either the intervention or control group using a computer script. Each team, regardless of group, performed two advanced life support (ALS) scenarios on a simulator. The two groups differed in the order in which they completed the flipped e-learning curriculum. The intervention group started with the e-learning component, and the control group started with an ALS scenario. Simulators were used for recording and analysing resuscitation performance indicators, while professionals assessed team performance as a primary outcome., Results: The analysis was conducted on the data of 96 participants in 21 teams, comprising of 11 intervention groups and 10 control groups. The intervention teams achieved higher team performance ratings during the first scenario compared to the control teams (Estimated marginal mean of global rating: 7.5 vs 5.6, p < 0.01; performance score: 4.4 vs 3.8, p < 0.05; global score: 4.4 vs 3.7, p < 0.001). However, these differences were not observed in the second scenario, where both study groups had used the e-learning tool., Conclusion: Flipped classroom approaches using learner-paced e-learning prior to hands-on training can improve team performance., Trial Registration: German Clinical Trials Register ( https://drks.de/search/de/trial/DRKS00013096 )., (© 2024. The Author(s).)

Background: Although effective treatments for bulimic-spectrum eating disorders exist, access is often delayed because of limited therapist availability and lengthy waiting lists. Web-based self-help interventions have the potential to bridge waiting times for face-to-face treatment and overcome existing treatment gaps., Aims: This study aims to assess the effectiveness of a web-based guided self-help intervention (everyBody Plus) for patients with bulimia nervosa, binge eating disorder and other specified feeding and eating disorders who are waiting for out-patient treatment., Method: A randomised controlled trial was conducted in Germany and the UK. A total of 343 patients were randomly assigned to the intervention 'everyBody Plus' or a waitlist control condition. The primary outcome was the number of weeks after randomisation until a patient achieved a clinically relevant improvement in core symptoms for the first time. Secondary outcomes included eating disorder attitudes and behaviours, and general psychopathology., Results: At 6- and 12-month follow-up, the probability of being abstinent from core symptoms was significantly larger for the intervention group compared with the control group (hazard ratio: 1.997, 95% CI 1.09-3.65; P = 0.0249). The intervention group also showed larger improvements in eating disorder attitudes and behaviours, general psychopathology, anxiety, depression and quality of life, compared with the control group at most assessment points. Working alliance ratings with the online therapist were high., Conclusions: The self-help intervention everyBody Plus, delivered with relatively standardised online guidance, can help bridge treatment gaps for patients with bulimic-spectrum eating disorders, and achieve faster and greater reductions in core symptoms.

There is an increasing number of potential quantitative biomarkers that could allow for early assessment of treatment response or disease progression. However, measurements of such biomarkers are subject to random variability. Hence, differences of a biomarker in longitudinal measurements do not necessarily represent real change but might be caused by this random measurement variability. Before utilizing a quantitative biomarker in longitudinal studies, it is therefore essential to assess the measurement repeatability. Measurement repeatability obtained from test-retest studies can be quantified by the repeatability coefficient, which is then used in the subsequent longitudinal study to determine if a measured difference represents real change or is within the range of expected random measurement variability. The quality of the point estimate of the repeatability coefficient, therefore, directly governs the assessment quality of the longitudinal study. Repeatability coefficient estimation accuracy depends on the case number in the test-retest study, but despite its pivotal role, no comprehensive framework for sample size calculation of test-retest studies exists. To address this issue, we have established such a framework, which allows for flexible sample size calculation of test-retest studies, based upon newly introduced criteria concerning assessment quality in the longitudinal study. This also permits retrospective assessment of prior test-retest studies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

HIV-1 infection requires nuclear entry of the viral genome. Previous evidence suggests that this entry proceeds through nuclear pore complexes (NPCs), with the 120 × 60 nm capsid squeezing through an approximately 60-nm-wide central channel 1 and crossing the permeability barrier of the NPC. This barrier can be described as an FG phase 2 that is assembled from cohesively interacting phenylalanine-glycine (FG) repeats 3 and is selectively permeable to cargo captured by nuclear transport receptors (NTRs). Here we show that HIV-1 capsid assemblies can target NPCs efficiently in an NTR-independent manner and bind directly to several types of FG repeats, including barrier-forming cohesive repeats. Like NTRs, the capsid readily partitions into an in vitro assembled cohesive FG phase that can serve as an NPC mimic and excludes much smaller inert probes such as mCherry. Indeed, entry of the capsid protein into such an FG phase is greatly enhanced by capsid assembly, which also allows the encapsulated clients to enter. Thus, our data indicate that the HIV-1 capsid behaves like an NTR, with its interior serving as a cargo container. Because capsid-coating with trans-acting NTRs would increase the diameter by 10 nm or more, we suggest that such a 'self-translocating' capsid undermines the size restrictions imposed by the NPC scaffold, thereby bypassing an otherwise effective barrier to viral infection., (© 2024. The Author(s).)

Introduction: Limited research exists on intervention efficacy for comorbid subclinical anxiety and depressive disorders, despite their common co-occurrence. Internet- and mobile-based interventions (IMIs) are promising to reach individuals facing subclinical symptoms., Objective: This study aimed to evaluate the efficacy of a transdiagnostic and self-tailored IMI in reducing subclinical anxiety and depressive symptom severity with either individualized (IG-IMI) or automated (AG-IMI) guidance compared to a waitlist control group with care-as-usual access (WLC)., Methods: Participants included 566 adults with subclinical anxiety (GAD-7 ≥ 5) and/or depressive (CES-D ≥16) symptoms, who did not meet criteria for a full-syndrome depressive or anxiety disorder. In a three-arm randomized clinical trial, participants were randomized to a cognitive behavioral 7-session IMI plus booster session with IG-IMI (n = 186) or AG-IMI (n = 189) or WLC (n = 191). Primary outcomes included observer-rated anxiety (HAM-A) and depressive (QIDS) symptom severity 8 weeks after randomization assessed by blinded raters via telephone. Follow-up outcomes at 6 and 12 months are reported., Results: Symptom severity was significantly lower with small to medium effects in IG-IMI (anxiety: d = 0.45, depression: d = 0.43) and AG-IMI (anxiety: d = 0.31, depression: d = 0.32) compared to WLC. No significant differences emerged between guidance formats in primary outcomes. There was a significant effect in HAM-A after 6 months favoring AG-IMI. On average, participants completed 85.38% of IG-IMI and 77.38% of AG-IMI., Conclusions: A transdiagnostic, self-tailored IMI can reduce subclinical anxiety and depressive symptom severity, but 12-month long-term effects were absent. Automated guidance holds promise for enhancing the scalability of IMIs in broad prevention initiatives., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Based on the Kidney Disease: Improving Global Outcomes (KDIGO) definitions, urine output, serum creatinine, and need for kidney replacement therapy are used for staging acute kidney injury (AKI). Currently, AKI staging correlates strongly with mortality and can be used as a predictive tool. However, factors associated with the development of AKI may affect its predictive ability. We tested whether adjustment for predicted (versus actual) body weight improved the ability of AKI staging to predict hospital mortality., Methods: A total of 3279 patients who had undergone cardiac surgery in a university hospital were retrospectively analyzed. AKI was staged according to KDIGO criteria (standard staging) and after adjustment for hourly urine output adjusted by predicted body weight for each patient and each day of their hospital stay., Results: The incidence of AKI (all stages) was 43% (predicted body weight adjusted) and 50% (standard staging), respectively ( P < .001). In sensitivity-specificity analyses for predicting hospital mortality, the area under the curve was significantly higher after adjustment for predicted body weight than with standard staging ( P = .002)., Conclusions: Compared to standard staging, adjustment of urine output for predicted body weight increases the specificity and improves prediction of hospital mortality in patients undergoing cardiac surgery., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)