Pathological Insights into Non-Neoplastic Renal Parenchyma in Wilms Tumor: Implications for Nephron-Sparing Surgery.

INTRODUCTION: This study aimed to evaluate the non-neoplastic renal parenchyma in Wilms tumor (WT) and investigate its impact on nephron-sparing surgery (NSS). MATERIALS AND METHODS: The non-neoplastic renal parenchyma of WT patients was prospectively collected for pathological examination. The histology of non-neoplastic renal parenchyma was assessed from two perspectives: nephrogenic rests (NRs) and nephrons. RESULTS: A total of 46 non-neoplastic renal parenchyma specimens were collected from 42 WT patients. The surgeons assessed the median proportion of non-neoplastic renal parenchyma as 30%, whereas using ellipsoid volume, it was calculated to be 27%. The Youden index of surgeons' assessment peaked at a 15% proportion of non-neoplastic renal parenchyma. The bilateral WT (BWT) group and NSS group exhibited significant differences compared with the unilateral WT group and radical nephrectomy group, respectively, with the BWT group showing a tendency toward thickened basement membrane. CONCLUSION: The presence of NRs and endogenous nephron alternations should be given due attention in WT. The probability of abnormalities is low when the proportion of non-neoplastic renal parenchyma exceeds 15%, providing pathological support for expanding the adaptation of NSS.

Trends in prevalence of hypertension and high-normal blood pressure among US adults, 1999-2018.

Hypertension and high-normal blood pressure (BP) increase the risk for cardiovascular diseases. Examining trends in hypertension and high-normal BP among US adults is crucial. Participants aged 20 years or older from the 1999-2018 National Health and Nutrition Examination Surveys, were included. Trend analyses were performed to assess temporal changes in prevalence of hypertension and high-normal BP among US adults. Among the 48,580 participants included in this analysis, the mean (SD) age was 47.2 years (18 years) and 50.9% were women. Age-adjusted prevalence of hypertension was stable from 1999 to 2000 (29.5% [95% CI 26.6-32.3%]) through 2017-2018 (31.9%, [95% CI 29.0-34.7%]) (P = 0.265 for linear trend). Age-adjusted prevalence of high-normal BP decreased from 10.9% (95% CI 9.4-12.5%) in 1999-2000 to 8.0% (95% CI 7.1-9.0%) in 2007-2008, then increased to 9.8% (95% CI 8.3-11.3%) in 2017-2018 (P = 0.002 for nonlinear trend). Compared with men, hypertension and high-normal BP was less likely among women (multivariable-adjusted prevalence ratio, 0.90 [95% CI 0.84-0.97]; 0.68 [95% CI 0.52-0.88], respectively). Compared with non-Hispanic Black, high-normal BP was less likely among Mexican American, non-Hispanic White, and other race (multivariable-adjusted prevalence ratio, 0.59 [95% CI 0.44-0.79]; 0.53 [95% CI 0.41-0.69]; 0.56 [95% CI 0.74 - 0.71], respectively). The same held for hypertension.

Pan-genome analyses of eleven Fraxinus species provide insights into salt adaptation in ash trees.

Ash trees (Fraxinus) exhibit rich genetic diversity and wide adaptation to various ecological environments, several of which are highly salt-tolerant. Dissecting the genomic basis underlying ash tree salt adaptation is vital for its resistance breeding. Here, we presented eleven high-quality chromosome-level genome assemblies for Fraxinus species, revealing two unequal sub-genome compositions and two more recent whole-genome triplication events in evolutionary history. A Fraxinus structural variation-based pan-genome was constructed and revealed that presence-absence variations (PAVs) of transmembrane transport genes likely contribute to Fraxinus salt adaptation. Through whole-genome resequencing of an inter-species cross F1-population of F. velutina 'Lula 3' (salt-tolerant) × F. pennsylvanica 'Lula 5' (salt-sensitive), we performed a salt tolerance PAV-based quantitative trait loci (QTL) mapping and pinpointed two PAV-QTLs and candidate genes associated with Fraxinus salt tolerance. Mechanismly, FvbHLH85 enhanced salt tolerance by mediating reactive oxygen species and Na+/K+ homeostasis, while FvSWEET5 by mediating osmotic homeostasis. Collectively, these findings provide valuable genomic resources for Fraxinus salt resistance breeding and research community.

The effectiveness of nirmatrelvir/ritonavir regimen in hospitalized renal transplant patients with prolonged COVID-19 infection: a multicenter clinical experience.

OBJECTIVES: Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated. METHODS: In this multicenter retrospective study, 85 KTRs with COVID-19 were enrolled, including 50 moderate, 21 severe, and 14 critical patients. RESULTS: The median time from onset to starting NR treatment was 14 (IQR, 11-19) days. Before NR treatment, 96.5% patients reduced use of antimetabolites. They also stopped using calcineurin inhibitors (CNI) 12-24 hours before NR treatment, with CNI concentrations well-controlled during NR treatment. The use of intravenous corticosteroids increased with COVID-19 severity. The median time to reach viral negative conversion was 5 (IQR, 4-8) days for all patients. For moderate and severe COVID-19 patients, they had a low rate of ICU admission (1.4%), exacerbation requiring upgraded oxygen therapy (5.6%), and dialysis (2.8%); no intubation and mechanical ventilation, and no deaths were observed. Patients with critical COVID-19 had a low mortality rate (7.1%). CONCLUSIONS: A regimen including NR for clearing SARS-CoV-2 along with reducing immunosuppressants and using intravenous corticosteroids is associated with lower rates of exacerbation and mortality in KTRs who have moderate to critical SARS-CoV-2 infection and the virus still present after 5 days.

Humic acid enhances the co-transport of colloids and phosphorus in saturated porous media.

Phosphorus (P) has been widely recognized as a substance that is difficult to transport due to its tendency to become easily fixed in the soil. However, many reports demonstrate that groundwater P pollution is rising in humus-rich areas. Research is urgently needed to confirm (or reject) the hypothesis that increased P pollution is related to humus, as there is currently limited quantitative research on this topic. In this study, we conducted a series of batch equilibrium adsorption-desorption experiments and column experiments to quantify the effects of montmorillonite colloids (MCs) and humic acids (HCs, the main components of humus) on the P transport behavior. The results indicate that P's adsorption and desorption behavior on MCs can be well simulated using the Langmuir and Temkin models (R2 > 0.91). Compared to the non-HC treatments, HCs significantly increased MCs' P adsorption and desorption capacity 5.18 and 7.21 times, respectively. Moreover, HCs facilitated the transport ability of the MC-P mixture through the saturated quartz sand column. In a 0.1 M NaCl solution, the MC-P mixture is nearly completely adsorbed on the surface of quartz sand, with a penetration rate of only 0.5%. In contrast, the HC-MC-P mixture can evidently penetrate further at a rate of 26.1%. The transport parameters fitted using HYDRUS-1D further indicated that the presence of humic acids significantly decreased the deposition coefficients of colloids, thereby enhancing the co-transport of colloids and P through the quartz sand porous medium. The potential mechanism of P pollution in humus-rich areas is likely enhanced by the formation of an HC-colloid-P mixture, which greatly increases the adsorption amount of P on colloids and enhances the electrostatic and spatial repulsion between colloids as well as between colloids and quartz sand. It reduces the aggregation and adsorption of colloids, ultimately transferring P into groundwater through colloid-facilitated co-transport. The findings of this study clarified the relationship between the transport of P, colloids, and HCs, which provides a theoretical basis for explaining the P pollution mechanism in humus-rich areas.

Dosing strategy of tacrolimus when co-administered with Wuzhi tablet in renal transplant recipients.

OBJECTIVE: Tacrolimus (TAC) is a first-line immunosuppressant to prevent allograft rejection. Wuzhi tablet is widely used as a TAC-sparing agent in China that could significantly elevate TAC exposure. However, insufficient data support the dose recommendation of TAC when co-administered with Wuzhi. MATERIALS AND METHODS: A total of 305 adult renal transplant patients with 2,541 TAC trough concentrations (C0) were enrolled for population pharmacokinetic (PPK) modeling. CYP3A5 polymorphism was genotyped, and corresponding clinical factors were recorded. Nonlinear mixed-effects modeling and Monte Carlo simulation were used for dose recommendation. PK parameters were calculated based on one-compartment model with first-order absorption and elimination. RESULTS: The estimated total clearance (CL/F) and volume of distribution (Vd/F) of TAC were 23.84 L/h and 1,075.96 L, respectively. Wuzhi, CYP3A5 genotype, hematocrit (HCT), and weight were found to have a significant influence on CL/F. CL/F was significantly lower in the individuals who were CYP3A5 non-expressers and received TAC together with Wuzhi. CYP3A5 genotype (expressers or non-expressers), body weight (40 - 80 kg), and hematocrit (20 - 40%) were selected as the specific clinical scenarios, and the starting dose of TAC ranged from 1.5 to 4.5 mg when co-administered with Wuzhi. CONCLUSION: We establish a TAC PPK model comprising Wuzhi as a covariate in renal transplant recipients and recommend an initial dose of TAC when co-administered with Wuzhi, which could provide reference for the individualized regimens of TAC.

Primary exophytic urothelial carcinoma of the bladder: A case report.

RATIONALE: Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients. PATIENT CONCERNS: An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss. DIAGNOSIS: Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC. INTERVENTIONS: The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy. OUTCOMES: The patient's mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery. LESSONS: UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.

JrPHL8-JrWRKY4-JrSTH2L module regulates resistance to Colletotrichum gloeosporioides in walnut.

Walnut anthracnose (Colletotrichum gloeosporioides) reduces walnut yield and quality and seriously threatens the healthy development of the walnut industry. WRKY transcription factors (TFs) are crucial regulatory factors involved in plant-pathogen interactions. Our previous transcriptome analysis results indicate that JrWRKY4 responds to infection by C. gloeosporioides, but its specific regulatory network and disease resistance mechanism are still unclear. Herein, the characteristics of JrWRKY4 as a transcription activator located in the nucleus were first identified. Gain-of-function and loss-of-function analyses showed that JrWRKY4 could enhance walnut resistance against C. gloeosporioides. A series of molecular experiments showed that JrWRKY4 directly interacted with the promoter region of JrSTH2L and positively regulated its expression. In addition, JrWRKY4 interacted with JrVQ4 to form the protein complex, which inhibited JrWRKY4 for the activation of JrSTH2L. Notably, a MYB TF JrPHL8 interacting with the JrWRKY4 promoter has also been identified, which directly bound to the MBS element in the promoter of JrWRKY4 and induced its activity. Our study elucidated a novel mechanism of the JrPHL8-JrWRKY4-JrSTH2L in regulating walnut resistance to anthracnose. This mechanism improves our understanding of the molecular mechanism of WRKY TF mediated resistance to anthracnose in walnut, which provides new insights for molecular breeding of disease-resistant walnuts in the future.

A dual RNA-seq analyses revealed dynamic arms race during the invasion of walnut by Colletotrichum gloeosporioides.

BACKGROUND: Walnut anthracnose caused by Colletotrichum gloeosporioides seriously endangers the yield and quality of walnut, and has now become a catastrophic disease in the walnut industry. Therefore, understanding both pathogen invasion mechanisms and host response processes is crucial to defense against C. gloeosporioides infection. RESULTS: Here, we investigated the mechanisms of interaction between walnut fruits (anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts) and C. gloeosporioides at three infection time points (24hpi, 48hpi, and 72hpi) using a high-resolution time series dual transcriptomic analysis, characterizing the arms race between walnut and C. gloeosporioides. A total of 20,780 and 6670 differentially expressed genes (DEGs) were identified in walnut and C. gloeosporioides against 24hpi, respectively. Generous DEGs in walnut exhibited opposite expression patterns between F26 and F423, which indicated that different resistant materials exhibited different transcriptional responses to C. gloeosporioides during the infection process. KEGG functional enrichment analysis indicated that F26 displayed a broader response to C. gloeosporioides than F423. Meanwhile, the functional analysis of the C. gloeosporioides transcriptome was conducted and found that PHI, SignalP, CAZy, TCDB genes, the Fungal Zn (2)-Cys (6) binuclear cluster domain (PF00172.19) and the Cytochrome P450 (PF00067.23) were largely prominent in F26 fruit. These results suggested that C. gloeosporioides secreted some type of effector proteins in walnut fruit and appeared a different behavior based on the developmental stage of the walnut. CONCLUSIONS: Our present results shed light on the arms race process by which C. gloeosporioides attacked host and walnut against pathogen infection, laying the foundation for the green prevention of walnut anthracnose.

Oxidized ATP Suppresses B Lymphocyte Activity to Attenuate Antibody-mediated Rejection of Kidney Allografts in Mice.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined. METHODS: Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry. RESULTS: Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells. CONCLUSIONS: These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.

Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients.

OBJECTIVES: To describe the pharmacokinetic (PK) characteristics of nirmatrelvir/ritonavir in renal transplant recipients and explore the potential factors that related to the PK variance of nirmatrelvir/ritonavir and its interaction with calcineurin inhibitor (CNI). METHODS: Renal transplant recipients treated with CNI and nirmatrelvir/ritonavir were prospectively enrolled. Steady-state plasma concentrations of nirmatrelvir/ritonavir were determined by high-performance liquid chromatography-tandem mass spectrometry, and the PK parameters were calculated using non-compartmental analysis. Spearman correlation analysis was used for exploring influencing factors. RESULTS: A total of eight recipients were enrolled; for nirmatrelvir and ritonavir, AUC/dose was 0.24179 ± 0.14495 and 0.06196 ± 0.03767 µg·h·mL-1·mg-1. Red blood cell (RBC), hematocrit (Ht), hemoglobins (Hb), and creatinine clearance (Ccr) were negatively correlated with AUC/dose of nirmatrelvir, while Ccr, CYP3A5 genotype, and CYP3A4 genotype were related to the AUC/dose of ritonavir. Ccr was negatively correlated with the C0/dose of tacrolimus (TAC) after termination of nirmatrelvir/ritonavir (rs = -0.943, p = 0.008). CONCLUSIONS: The PK characteristics of nirmatrelvir/ritonavir vary greatly among renal transplant recipients. Factors including Ccr and CYP3A5 genotype were related to the in vivo exposure of nirmatrelvir/ritonavir. During the whole process before and after nirmatrelvir/ritonavir therapy, it is recommended to adjust the CNI basing on renal function to avoid CNI toxicity exposure.

The effect of retirement on physical and mental health in China: a nonparametric fuzzy regression discontinuity study.

BACKGROUND: With the rapid aging of the domestic population, China has a strong incentive to increase the statutory retirement age. How retirement affects the health of the elderly is crucial to this policymaking. The health consequences of retirement have been debated greatly. This study aims to investigate the effects of retirement on physical and mental health among Chinese elderly people. METHODS: The data we use in this study comes from four waves (2011, 2013, 2015, and 2018) of the Harmonized China Health and Retirement Longitudinal Study (Harmonized CHARLS), a prospective cohort. We use the nonparametric fuzzy regression discontinuity design to estimate the effects of retirement on physical and mental health. We test the robustness of our results with respect to different bandwidths, kernel functions, and polynomial orders. We also explore the heterogeneity across gender and education. RESULTS: Results show that retirement has an insignificant effect on a series of physical and mental health outcomes, with and without adjusting several sociodemographic variables. Heterogeneity exists regarding gender and education. Although stratified analyses indicate that the transition from working to retirement leaves minimal effects on males and females, the effects go in the opposite direction. This finding holds for low-educated and high-educated groups for health outcomes including depression and cognitive function. Most of the results are stable with respect to different bandwidths, kernel functions, and polynomial orders. CONCLUSIONS: Our results suggest that it is possible to delay the statutory retirement age in China as retirement has insignificant effects on physical and mental health. However, further research is needed to assess the long-term effect of retirement on health.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Quantitative analysis and stochastic modeling of osteophyte formation and growth process on human vertebrae based on radiographs: a follow-up study.

Osteophytes are frequently observed in elderly people and most commonly appear at the anterior edge of the cervical and lumbar vertebrae body. The anterior osteophytes keep developing and will lead to neck/back pain over time. In clinical practice, the accurate measurement of the anterior osteophyte length and the understanding of the temporal progression of anterior osteophyte growth are of vital importance to clinicians for effective treatment planning. This study proposes a new measuring method using the osteophyte ratio index to quantify anterior osteophyte length based on lateral radiographs. Moreover, we develop a continuous stochastic degradation model with time-related functions to characterize the anterior osteophyte formation and growth process on cervical and lumbar vertebrae over time. Follow-up data of anterior osteophytes up to 9 years are obtained for measurement and model validation. The agreement test indicates excellent reproducibility for our measuring method. The proposed model accurately fits the osteophyte growth paths. The model predicts the mean time to onset of pain and obtained survival function of the degenerative vertebrae. This research opens the door to future quantification and mathematical modeling of the anterior osteophyte growth on human cervical and lumbar vertebrae. The measured follow-up data is shared for future studies.

Healthcare facilities management: A novel data-driven model for predictive maintenance of computed tomography equipment.

BACKGROUND: The breakdown of healthcare facilities is a huge challenge for hospitals. Medical images obtained by Computed Tomography (CT) provide information about the patients' physical conditions and play a critical role in diagnosis of disease. To deliver high-quality medical images on time, it is essential to minimize the occurrence frequencies of anomalies and failures of the equipment. METHODS: We extracted the real-time CT equipment status time series data such as oil temperature, of three equipment, between May 19, 2020, and May 19, 2021. Tube arcing is treated as the classification label. We propose a dictionary-based data-driven model SAX-HCBOP, where the two methods, Histogram-based Information Gain Binning (HIGB) and Coefficient improved Bag of Pattern (CoBOP), are implemented to transform the data into the bag-of-words paradigm. We compare our model to the existing predictive maintenance models based on statistical and time series classification algorithms. RESULTS: The results show that the Accuracy, Recall, Precision and F1-score of the proposed model achieve 0.904, 0.747, 0.417, 0.535, respectively. The oil temperature is identified as the most important feature. The proposed model is superior to other models in predicting CT equipment anomalies. In addition, experiments on the public dataset also demonstrate the effectiveness of the proposed model. CONCLUSIONS: The two proposed methods can improve the performance of the dictionary-based time series classification methods in predictive maintenance. In addition, based on the proposed real-time anomaly prediction system, the model assists hospitals in making accurate healthcare facilities maintenance decisions.

Value of original and modified pathological scoring systems for prognostic prediction in paraffin-embedded donor kidney core biopsy.

BACKGROUND: No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy. METHODS: A total of 185 donor kidney CB specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores. RESULTS: The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59, p < 0.001; PGF: OR = 1.06, p = 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems. CONCLUSIONS: Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section.

The Association Between the Albumin-Bilirubin Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). We retrospectively observed 5629 patients undergoing elective PCI. Contrast-associated acute kidney injury is defined as a 50% or 0.3 mg/dl increase in baseline serum creatinine levels within 48 h of contrast exposure. The incidence of CA-AKI was 6.2% (n = 350). After adjusting for potential confounding factors, multivariate analysis showed that the ALBI score was an independent predictor of CA-AKI (P = .002). A restricted cubic spline analysis confirmed approximately linear relationships between the ALBI score and risks of CA-AKI. Furthermore, at a median follow-up of 2.8 years, multivariate Cox regression analysis indicated that the ALBI score was an independent risk factor for long-term mortality (P < .001). The ALBI score was closely related to the occurrence of CA-AKI and long-term mortality in patients who underwent elective PCI. This score might be useful for risk stratification in high-risk patient groups to predict CA-AKI.

A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients.

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

Prognostic Biomarkers in Kidney Transplantation: A Systematic Review and Critical Appraisal.

SIGNIFICANCE STATEMENT: Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events. Less than 5% of the studies performed an external validation. The authors also showed the poor transparency reporting and identified a data beautification phenomenon. These findings suggest that there is much wasted research effort in transplant biomarker medical research and highlight the need to produce more rigorous studies so that more biomarkers may be validated and successfully implemented in clinical practice. BACKGROUND: Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology, and reporting might contribute to this phenomenon. METHODS: We formed a consortium of experts in systematic reviews, nephrologists, methodologists, and epidemiologists. A systematic literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library between January 1, 2005, and November 12, 2022 (PROSPERO ID: CRD42020154747). All English language, original studies investigating the association between a biomarker and kidney allograft outcome were included. The final set of publications was assessed by expert reviewers. After data collection, two independent reviewers randomly evaluated the inconsistencies for 30% of the references for each reviewer. If more than 5% of inconsistencies were observed for one given reviewer, a re-evaluation was conducted for all the references of the reviewer. The biomarkers were categorized according to their type and the biological milieu from which they were measured. The study characteristics related to the design, methods, results, and their interpretation were assessed, as well as reproducible research practices and transparency indicators. RESULTS: A total of 7372 publications were screened and 804 studies met the inclusion criteria. A total of 1143 biomarkers were assessed among the included studies from blood ( n =821, 71.8%), intragraft ( n =169, 14.8%), or urine ( n =81, 7.1%) compartments. The number of studies significantly increased, with a median, yearly number of 31.5 studies (interquartile range [IQR], 23.8-35.5) between 2005 and 2012 and 57.5 (IQR, 53.3-59.8) between 2013 and 2022 ( P < 0.001). A total of 655 studies (81.5%) were retrospective, while 595 (74.0%) used data from a single center. The median number of patients included was 232 (IQR, 96-629) with a median follow-up post-transplant of 4.8 years (IQR, 3.0-6.2). Only 4.7% of studies were externally validated. A total of 346 studies (43.0%) did not adjust their biomarker for key prognostic factors, while only 3.1% of studies adjusted the biomarker for standard-of-care patient monitoring factors. Data sharing, code sharing, and registration occurred in 8.8%, 1.1%, and 4.6% of studies, respectively. A total of 158 studies (20.0%) emphasized the clinical relevance of the biomarker, despite the reported nonsignificant association of the biomarker with the outcome measure. A total of 288 studies assessed rejection as an outcome. We showed that these rejection studies shared the same characteristics as other studies. CONCLUSIONS: Biomarker studies in kidney transplantation lack validation, rigorous design and methodology, accurate interpretation, and transparency. Higher standards are needed in biomarker research to prove the clinical utility and support clinical use.