Acute kidney injury (AKI) following cardiac surgery is common and is associated with poor outcomes. The combination of urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) is a strong predictor of AKI after cardiac surgery. However, most studies have focused on non-Asian populations, and comparisons with other AKI biomarkers or the optimal timing for measurement have yet to be explored.

We prospectively enrolled adult patients at Kochi Medical School Hospital in Kochi, Japan, to assess the predictive values of [TIMP-2]•[IGFBP7], TIMP-2, IGFBP7, neutrophil gelatinase-associated lipocalin (NGAL), and liver fatty acid-binding protein (L-FABP) measured preoperatively and at 2, 4, 6, and 8 h, as well as on day 1 and day 2 after postoperative intensive care unit (ICU) admission, using receiver operating characteristic curve (ROC) analysis.

Of the 38 patients, 13 (34.2%) developed AKI: seven (18.4%) with stage 1, four (10.5%) with stage 2, and two (5.2%) with stage 3. ROC analysis showed that the area under the curve (AUC) for predicting any stage of AKI peaked at 0-4 h, with the highest value at 2 h after ICU admission. Among the biomarkers, [TIMP-2]•[IGFBP7] showed the best AUC at 2 h after ICU admission, followed by TIMP-2, IGFBP7, L-FABP, and NGAL.

Our study demonstrated the good predictive performance of urine biomarkers, including [TIMP-2]•[IGFBP7], TIMP-2, IGFBP7, NGAL, and L-FABP, for any stage of cardiac surgery-associated AKI (CSA-AKI). The combination of TIMP-2 and IGFBP7 measured 2 h after postoperative ICU admission effectively predicted CSA-AKI, identifying patients at higher risk.

Sodium-glucose transporter-2 (SGLT2) inhibitors reduced the incidence of acute kidney injury in large cardiovascular outcome trials in patients with chronic heart and kidney failure. Acute kidney injury is a common complication following cardiac surgery. We hypothesized that perioperative SGLT2 inhibition could reduce kidney injury after cardiac surgery, measured with the biomarker neutrophil gelatinase-associated (NGAL).

In this open-label phase IV, randomized, parallel-group, pilot study, adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive either an SGLT2 inhibitor, empagliflozin (10 mg; oral) once daily, from three days before surgery until postoperative day two, or standard-of-care. The primary outcome was the between-group difference of serum NGAL on the second postoperative day. Moreover, other biomarkers for acute kidney injury were measured, including serum kidney injury molecule-1 (KIM-1), hypoxia-inducible factor-1 alpha (HIF-1α), and urine NGAL/Creatinine and KIM-1/Creatinine ratios. Additional outcomes included acute kidney injury incidence within the first seven days following cardiac surgery according to Kidney Disease: Improving Global Outcomes criteria and metabolic parameters, including ketone body concentrations and glycemic control.

Between March 2022 and April 2023, 55 patients were included (sex: 73 % male, age: 66 ± 10 years, BMI: 28 ± 4 kg/m2, empagliflozin n = 25, control n = 30) in the intention-to-treat analysis. There were no significant between-group differences in serum and urine NGAL or KIM-1. However, empagliflozin significantly reduced the incidence of acute kidney injury (20 % vs 66.7 %; absolute difference 46.7 %, 95 % CI, -69.7 - -23.6; P < .001). A significant increase in serum HIF-1α after surgery was solely observed in the control group. We observed no between-group differences in the incidence of (euglycemic) ketoacidosis or hypoglycemic events.

In this pilot study, perioperative SGLT2 inhibition was not associated with lower NGAL levels. We observed that SGLT2 inhibition reduced the incidence of acute kidney injury in this small study population. As the results of this pilot study are hypotheses-generating, further validation is needed in a large-scale, double-blind, placebo-controlled, randomized trial, which is currently ongoing.

Creatinine-to-albumin ratio (CAR) has been recognized as a predictive indicator in the postoperative setting. However, its relationship with outcomes in patients receiving cardiac surgery remains elusive. This study aimed to discuss the link between CAR and 28-day mortality in patients admitted to intensive care unit (ICU) following cardiac surgery, hoping to provide some insights for targeted interventions for improvement of patient outcomes.

MIMIC-IV database was searched to obtain data of patients admitted to ICU following cardiac surgery. Retrieved patients were split into three groups based on CAR levels. The 28-day ICU mortality in each group was evaluated and compared using Kaplan-Meier analysis. Subgroup analysis, multivariate Cox regression and restricted cubic spline (RCS) analysis were used to further examine the relationship between CAR and outcomes. Receiver operating characteristic (ROC) curves were used to assess the predictive ability of CAR. Mediation analysis was conducted to investigate the potential mechanism by which CAR affects 28-day ICU mortality.

A total of 5,670 patients were included and divided into three groups. Patients with high CAR values (CAR ≥ 0.31) had a significantly increased rate of 28-day ICU mortality (11.4%), as compared to those with low CAR levels (CAR < 0.23, 1.83%). In addition, patients with high CAR values (CAR ≥ 0.31) had a lowest survival rate than the other two groups (p < 0.0001). ROC curve analysis showed that CAR exhibited a moderate predictive power (AUC = 0.748). Moreover, CAR was identified as a strong risk factor for 28-day ICU mortality, and a significant dose-response association was presented. Further subgroup analysis revealed pronounced mortality risks in females and patients without chronic conditions such as chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Mediation analysis indicated that CAR affected 28-day ICU mortality through biomarkers like chloride (39.8%), glucose (11.8%), potassium (24.4%), and sodium (28.3%).

CAR served as a risk factor for 28-day ICU mortality in patients receiving cardiac surgery, and it showed a complex dose-response and subgroup-specific association with 28-day ICU mortality. Additionally, CAR affected 28-day ICU mortality through multiple key biomarkers, providing some insights for targeted interventions.

The study aimed to develop a risk prediction model through screening preoperative risk factors for acute kidney injury (AKI) after heart valve replacement in patients with normal renal function.

A total of 608 patients with normal renal function who underwent heart valve replacement from November 2013 to June 2022 were analyzed retrospectively. The Lasso regression was used to preliminarily screen potential risk factors, which were entered into the multivariable logistic regression analysis to identify preoperative independent risk factors for postoperative AKI. Based on the results, a risk prediction model was developed, and traditional and dynamic nomograms were constructed. The risk prediction model was evaluated using receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA).

220 patients (36.2%) developed AKI after surgery. Current smoker, hypertension, heart failure, previous myocardial infarction, cerebrovascular disease, CysC, and NT-proBNP were selected as independent risk factors for AKI. A risk prediction model, a traditional and a dynamic nomogram were developed based on the above factors. The area under the curve (AUC) of the ROC for predicting the risk of postoperative AKI was 0.803 (95% CI 0.769-0.836), with sensitivity and specificity of 84.9% and 63.4%, respectively. The calibration curve slope was close to 1, and the DCA showed that the model produced better clinical benefits when the probability threshold was set at 10%-82%.

We developed a preoperative risk prediction model for AKI after heart valve replacement in patients with normal renal function, which demonstrated satisfactory discrimination and calibration.

Acute kidney injury (AKI) is a frequent clinical complication lacking early diagnostic tests and effective treatments. Novel biomarkers have shown promise for enabling earlier detection, risk stratification, and guiding management of AKI. We conducted a systematic review to synthesize evidence on the efficacy of novel biomarkers for AKI detection and management. Database searches yielded 17 relevant studies which were critically appraised. Key themes were biomarker efficacy in predicting AKI risk and severity before functional changes; potential to improve clinical management through earlier diagnosis, prognostic enrichment, and guiding interventions; emerging roles as therapeutic targets and prognostic tools; and ongoing challenges requiring further validation. Overall, novel biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cell cycle arrest markers ([TIMP-2] •[IGFBP7]) demonstrate capability for very early AKI prediction and accurate risk stratification. Their incorporation has potential to facilitate timely targeted interventions and personalized management. However, factors influencing biomarker performance, optimal cutoffs, cost-effectiveness, and impact on patient outcomes require robust validation across diverse settings before widespread implementation. Addressing these limitations through ongoing research can help translate novel biomarkers into improved detection, prognosis, and management of AKI in clinical practice.

The objective of this study was to develop and validate a nomogram model integrating clinical, biochemical and ultrasound features to predict the malignancy rates of Thyroid Imaging Reporting and Data System 4 (TR4) thyroid nodules.

A total of 1557 cases with confirmed pathological diagnoses via fine-needle aspiration (FNA) were retrospectively included. Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of malignancy. These predictors were incorporated into the nomogram model, and its predictive performance was evaluated using receiver-operating characteristic curve (AUC), calibration plots, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA).

Eight out of 22 variables-age, margin, extrathyroidal extension, halo, calcification, suspicious lymph node metastasis, aspect ratio and thyroid peroxidase antibody-were identified as independent predictors of malignancy. The calibration curve demonstrated excellent performance, and DCA indicated favourable clinical utility. Additionally, our nomogram exhibited superior predictive ability compared to the current American College of Radiology (ACR) score model, as indicated by higher AUC, NRI, IDI, negative likelihood ratio (NLR) and positive likelihood ratio (PLR) values.

The developed nomogram model effectively predicts the malignancy rate of TR4 thyroid nodules, demonstrating promising clinical applicability.

Acute kidney dysfunction is commonly encountered in advanced heart failure and carries significant prognostic implications, often leading to poorer outcomes and increased mortality. It can alter the course of decision making for left ventricular assist device (LVAD) and cardiac transplantation candidacy. Kidney replacement therapies (KRT) offer a critical intervention in this context but require careful consideration of timing, various types of KRT modalities, individual patient preferences and circumstances. This review discusses the intricacies of KRT in advanced heart failure, examining how to optimize timing and choose among the various KRT modalities. It also provides a detailed discussion on the unique clinical scenarios that clinicians may face when treating this vulnerable patient group.

Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2).

Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77-0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85-0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82-0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05).

As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI.

Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1 .

Cell cycle arrest biomarkers (tissue inhibitor of metalloproteinase-2 [uTIMP-2] and insulin-like growth factor binding protein 7 [uIGFBP7]), and neutrophil gelatinase-associated lipocalin (NGAL) variables are valuable biomarkers for early diagnosis of acute kidney injury (AKI) in people.

To evaluate uTIMP-2, uIGFBP7, fractional excretion of NGAL (FeNGAL), and urinary to serum NGAL ratio (u/sNGAL) in healthy dogs, dogs with AKI, dogs with chronic kidney disease (CKD), and critically ill (CI) dogs.

Forty-two client-owned dogs (healthy, n = 10; AKI, n = 11; CKD, n = 11; CI, n = 10).

Prospective, observational study. After assessment of routine renal biomarkers, stress (uTIMP-2, uIGFBP7) and damage (NGAL) biomarkers were measured, using ELISA kits, and normalized to urinary creatinine (uCr).

Normalized uTIMP-2 and [uTIMP-2] × [uIGFBP7]/uCr were significantly higher in the AKI group (median 151.9 [range, 2.2-534.2] and 62.9 [1.1-266.8] pg/mL respectively), compared to healthy dogs (0.3 [0.2-74.7]; P < .001 and 0.16 [0.1-58.1] pg/mL; P < .001), dogs with CKD (0.7 [0.3-742.5]; P = .04 and 0.37 [0.2-180.1] pg/mL; P = .03) and CI dogs (1.9 [0.2-37.0]; P = .03 and 0.8 [0.1-16.1] pg/mL; P = .02). Fractional excretion of NGAL was significantly higher in dogs with AKI (54.17 [7.93-155.32] %), than in healthy (0.03 [0.01-0.21] %; P < .001) and CI dogs (3.05 [0.05-28.86] %; P = .02).

Normalized uTIMP-2, [uTIMP-2] × [uIGFBP7]/uCr, and FeNGAL can be valuable renal biomarkers for early diagnosis of AKI in dogs.

Chronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of chronic kidney disease (CKD) affecting young individuals mostly in agricultural communities in Central America and South Asia. CKDu is a diagnosis of exclusion made in individuals from endemic regions.

We conducted a systematic review of the primary literature on urinary and plasma kidney injury biomarkers measured in the setting of CKDu (through February 2023). The literature was identified via a Web of Science search and hand search of the references of previously identified literature. Search terms included "CKDu," "Mesoamerican Nephropathy," "CKD of unknown etiology," "Chronic Interstitial Nephritis in Agricultural Communities," "biomarker," "urin∗," and/or "plasma."

A total of 25 papers were included. The 2 most frequently measured biomarkers were urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL). There was substantial variability in study design, laboratory assay methods, and statistical methodology, which prohibited meta-analysis.

Biomarkers that identify tubulointerstitial disease early and accurately may substantially accelerate progress in the study of CKDu and facilitate public health approaches that eventually lead to its prevention and elimination. To date, the literature is limited by relatively small sample sizes and methodological limitations which should be addressed in future studies.

The objective of this investigation was to construct and validate a nomogram for prognosticating cancer-specific survival (CSS) in patients afflicted with gastrointestinal stromal tumor (GIST) at 3-, 5-, and 8-years post-diagnosis.

Data pertaining to patients diagnosed with GIST were acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Through random selection, a training cohort (70%) and a validation cohort (30%) were established from the patient population. Employing a backward stepwise Cox regression model, independent prognostic factors were identified. Subsequently, these factors were incorporated into the nomogram to forecast CSS rates at 3-, 5-, and 8-years following diagnosis. The nomogram's performance was assessed using indicators such as the consistency index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis (DCA).

This investigation encompassed a cohort of 3,062 GIST patients. By analyzing the Cox regression model within the training cohort, nine prognostic factors were identified: age, sex, race, marital status, AJCC (American Joint Committee on Cancer) stage, surgical status, chemotherapy status, radiation status, and income status. The nomogram was subsequently developed and subjected to both internal and external validation. The nomogram exhibited favorable discrimination abilities, as evidenced by notably high C-indices and AUC values. Calibration curves confirmed the nomogram's reliability. Moreover, the nomogram outperformed the AJCC model, as demonstrated by enhanced NRI and IDI values. The DCA curves validated the clinical utility of the nomogram.

The present study has successfully constructed and validated the initial nomogram for predicting prognosis in GIST patients. The nomogram's performance and practicality suggest its potential utility in clinical settings. Nevertheless, further external validation is warranted.

Whole blood analysis can evaluate numerous parameters, including pH, pCO₂, pO₂, HCO₃ - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep (Ovis aries) is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO₂, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female Ovis arie s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.

Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction, one of the most common complications of this surgical cohort. Acute kidney injury (AKI) is associated with increased short-term morbidity and mortality and has been the focus of much research. There is increasing recognition of the role of AKI as the key pathophysiological state leading to the disease entities acute and chronic kidney disease (AKD and CKD). In this narrative review, we will consider the epidemiology of renal dysfunction after cardiac surgery on CPB and the clinical manifestations across the spectrum of disease. We will discuss the transition between different states of injury and dysfunction, and, importantly, the relevance to clinicians. The specific facets of kidney injury on extracorporeal circulation will be described and the current evidence evaluated for the use of perfusion-based techniques to reduce the incidence and mitigate the complications of renal dysfunction after cardiac surgery.

Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratification tools for pediatric AKI, and outline opportunities for integration into clinical practice. We also summarize pediatric-specific high-risk diagnoses and exposures for AKI, as well as the potential role of real-time risk stratification and clinical decision support to improve outcomes. Lastly, the key characteristics of important pediatric AKI phenotypes will be outlined. Throughout, we identify key knowledge gaps, which represent prioritized areas of focus for future research that will facilitate a comprehensive, timely and personalized approach to pediatric AKI diagnosis and management.

The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR).

A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up.

Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC) > 0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n = 49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P < .001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P < .0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P = .095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly.

pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging. Hence, the current guidelines are still developing to improve and understand the clinical implications of risk factors and earlier predictive biomarkers of acute kidney injury. Yet, studies have indicated disadvantages and limitations with the current acute kidney injury biomarkers, including lack of sensitivity and specificity. Therefore, the present narrative review brings together the most current evidenced-based practice and literature associated with the limitations of the gold standard for acute kidney injury diagnoses, the need for novel acute kidney injury biomarkers, and the process for biomarkers to be qualified for diagnostic use under the following sections and themes. The introduction section situates the anatomy and normal and abnormal kidney functions related to acute kidney injury disorders. Guidelines in providing acute kidney injury definitions and classification are then considered, followed by a discussion of the disadvantages of standard markers used to diagnose acute kidney injury. Characteristics of an ideal acute kidney injury biomarker are discussed concerning sensitivity, specificity, and anatomic location of injury. A particular focus on the role and function of emerging biomarkers is discussed in relation to their applications and significance to the prognosis and severity of acute kidney injury. Findings show emerging markers are early indicators of acute kidney injury prediction in different clinical settings. Finally, the process required for a biomarker to be applied for diagnostic use is explained.

Acute kidney injury (AKI) remains a complex challenge with diverse underlying pathological mechanisms and etiologies. Current detection methods predominantly rely on serum creatinine, which exhibits substantial limitations in specificity and poses the issue of late-stage detection of kidney injury. In this review, we propose an up-to-date and comprehensive summary of advancements that identified novel biomarker candidates in blood and urine and ideal criteria for AKI biomarkers such as renal injury specificity, mechanistic insight, prognostic capacity, and affordability. Recently identified biomarkers not only indicate injury location but also offer valuable insights into a range of pathological processes, encompassing reduced glomerular filtration rate, tubular function, inflammation, and adaptive response to injury. The clinical applications of AKI biomarkers are becoming extensive and serving as relevant tools in distinguishing acute tubular necrosis from other acute renal conditions. Also, these biomarkers can offer significant insights into the risk of progression to chronic kidney disease CKD and in the context of kidney transplantation. Integration of these biomarkers into clinical practice has the potential to improve early diagnosis of AKI and revolutionize the design of clinical trials, offering valuable endpoints for therapeutic interventions and enhancing patient care and outcomes.

Despite the long-lasting notion about the substantial contribution of intraoperative un-stabilization of homeostasis factors on the incidence on acute kidney injury (AKI), the possible influence of intraoperative glucose or lactate management, as a modifiable factor, on the development of AKI remains inconclusive.

To investigated the relationship between intraoperative hyperglycemia, hyperlactatemia, and postoperative AKI in cardiac surgery.

A retrospective cohort study was conducted among 4,435 adult patients who underwent on-pump cardiac surgery from July 2019 to March 2022. Intraoperative hyperglycemia and hyperlactatemia were defined as blood glucose levels >10 mmol/L and lactate levels >2 mmol/L, respectively. The primary outcome was the incidence of AKI. All statistical analyses, including t tests, Wilcoxon rank sum tests, chi-square tests, Fisher's exact test, Kolmogorov-Smirnov test, logistic regression models, subgroup analyses, collinearity analysis, and receiver operating characteristic analysis, were performed using the statistical software program R version 4.1.1.

Among the 4,435 patients in the final analysis, a total of 734 (16.55%) patients developed AKI after on-pump cardiac surgery. All studied intraoperative metabolic disorders was associated with increased AKI risk, with most pronounced odds ratio (OR) noted for both hyperglycemia and hyperlactatemia were present intraoperatively [adjusted OR 3.69, 95% confidence intervals (CI) 2.68-5.13, p < 0.001]. Even when hyperglycemia or hyperlactatemia was present alone, the risk of postoperative AKI remained elevated (adjusted OR 1.97, 95% CI 1.50-2.60, p < 0.001).

The presence of intraoperative hyperglycemia and hyperlactatemia may be associated with postoperative acute kidney injury (AKI) in patients undergoing on-pump cardiac surgery. Proper and timely interventions for these metabolic disorders are crucially important in mitigating the risk of AKI.

Critical care nephrology is a subspecialty that merges critical care and nephrology in response to shared pathobiology, clinical care, and technological innovations. To date, there has been no description of the highest impact articles. Accordingly, we systematically identified high impact articles in critical care nephrology.

This was a bibliometric analysis. The search was developed by a research librarian. Web of Science was searched for articles published between January 1, 2000 and December 31, 2020. Articles required a minimum of 30 citations, publication in English language, and reporting of primary (or secondary) original data. Articles were screened by two reviewers for eligibility and further adjudicated by three experts. The "Top 100" articles were hierarchically ranked by adjudication, citations in the 2 years following publication and journal impact factor (IF). For each article, we extracted detailed bibliometric data. Risk of bias was assessed for randomized trials by the Cochrane Risk of Bias tool. Analyses were descriptive.

The search yielded 2,805 articles. Following initial screening, 307 articles were selected for full review and adjudication. The Top 100 articles were published across 20 journals (median [IQR] IF 10.6 [8.9-56.3]), 38% were published in the 5 years ending in 2020 and 62% were open access. The agreement between adjudicators was excellent (intraclass correlation, 0.96; 95% CI, 0.84-0.99). Of the Top 100, 44% were randomized trials, 35% were observational, 14% were systematic reviews, 6% were nonrandomized interventional studies and one article was a consensus document. The risk of bias among randomized trials was low. Common subgroup themes were RRT (42%), AKI (30%), fluids/resuscitation (14%), pediatrics (10%), interventions (8%), and perioperative care (6%). The citations for the Top 100 articles were 175 (95-393) and 9 were cited >1,000 times.

Critical care nephrology has matured as an important subspecialty of critical care and nephrology. These high impact papers have focused largely on original studies, mostly clinical trials, within a few core themes. This list can be leveraged for curricula development, to stimulate research, and for quality assurance.

People with HIV (PWH) generally have worse ambulatory levels of kidney injury biomarkers and excess risk of acute kidney injury (AKI) compared to persons without HIV. We evaluated whether ambulatory measures of subclinical kidney injury among PWH are associated with subsequent AKI.

In the Predictors of Acute Renal Injury Study (PARIS), which enrolled 468 PWH from April 2016 to August 2019, we measured 10 urine biomarkers of kidney health (albumin, a1m, b2M, NGAL, IL18, KIM-1, EGF, UMOD, MCP-1, YKL40) at baseline and annually during follow-up. Using multivariable Cox regression models, we evaluated baseline and time-updated biomarker associations with the primary outcome of AKI (≥0.3 mg/dl or ≥1.5-times increase in serum creatinine from baseline) and secondary outcome of all-cause hospitalization.

At baseline, the mean age was 53 years old, and 45% self-identified as female. In time-updated models adjusting for sociodemographic factors, comorbidities, albuminuria, estimated glomerular filtration rate, and HIV-associated factors, higher KIM-1 [hazard ratio (HR) = 1.30 per twofold higher; 95% confidence interval (CI) 1.03-1.63] and NGAL concentrations (HR = 1.24, 95% CI 1.06-1.44) were associated with higher risk of hospitalized AKI. Additionally, in multivariable, time-updated models, higher levels of KIM-1 (HR = 1.19, 95% CI 1.00, 1.41), NGAL (HR = 1.13, 95% CI 1.01-1.26), and MCP-1 (HR = 1.20, 95% CI 1.00, 1.45) were associated with higher risk of hospitalization.

Urine biomarkers of kidney tubular injury, such as KIM-1 and NGAL, are strongly associated with AKI among PWH, and may hold potential for risk stratification of future AKI.

The timely identification of patients at risk of acute kidney injury (AKI), along with early prevention, real-time monitoring, and prompt intervention, plays a crucial role in enhancing patient prognosis after major surgery.

We conducted a comprehensive search across multiple databases, including Web of Science, EMBASE, MEDLINE, China National Knowledge Infrastructure, and Cochrane Library. Each study's risk of bias was independently evaluated as low, moderate, or high, utilizing criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2. The analysis was performed using STATA V.17.0 and R software V.3.4.1. Diagnostic tests were ranked based on the dominance index. We performed meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. We then carried out a network meta-analysis to compare the performances of these biomarkers.

Fifteen studies were included in this analysis. The meta-analysis findings revealed that among all the biomarkers assessed, serum cystatin C (s-CysC) (hierarchical summary receiver operating characteristic curve [HSROC] 82%, 95% CI 0.78-0.85) exhibited the highest HSROC value. The network meta-analysis demonstrated that urinary kidney injury molecule-1 (u-KIM-1) and s-CysC displayed relatively higher sensitivity and specificity, respectively. In subgroup analyses, u-KIM-1 in the urine output (OU) group (OR 303.75, 95% CI 3.39-1844.88), s-CysC in the non-OU group (OR 10.31, 95% CI 3.09-26.2), interleukin-18 in the noncardiac surgery group (OR 46.20, 95% CI 0.48-307.68), s-CysC in the cardiac group (OR 12.42, 95% CI 2.9-35.86), u-KIM-1 in the retrospective group (OR 243.00, 95% CI 1.73-1582.11), and s-CysC in the prospective group (OR 8.35, 95% CI 2.34-21.15) had the best diagnostic accuracy. However, it is important to note that existing publication bias may reduce the reliability of the above-mentioned results.

The biomarker of s-CysC has the highest HSROC value to predicting acute kidney injury after major surgery in meta-analysis and relatively higher specificity in network meta-analyses. u-KIM-1 exhibited relatively higher sensitivity, with best diagnostic accuracy in the OU and retrospective group in the subgroup analysis.

Acute kidney injury (AKI) is a frequently occurring complication of cardiovascular interventions, and associated with adverse outcomes. Therefore, a clear definition of AKI is of paramount importance to enable timely recognition and treatment. Historically, changes in the serum creatinine and urine output have been used to define AKI, and the criteria have evolved over time with better understanding of the impact of AKI on the outcomes. However, the reliance on serum creatinine for these AKI definitions carries numerous limitations including delayed rise, inability to differentiate between hemodynamics versus structural injury and assay variability to name a few.

Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and overall mortality. Consequently, there has been a growing interest in uromodulin as a novel and effective biomarker with potential applications in diverse clinical settings. Reduced urinary uromodulin levels have been linked to an elevated risk of acute kidney injury (AKI) following cardiac surgery. In the context of chronic kidney disease (CKD) of different etiologies, urinary uromodulin levels tend to decrease significantly and are strongly correlated with variations in estimated glomerular filtration rate. The presence of uromodulin in the serum, attributable to basolateral epithelial cell leakage in the thick ascending limb, has been observed. This serum uromodulin level is closely associated with kidney function and histological severity, suggesting its potential as a biomarker capable of reflecting disease severity across a spectrum of kidney disorders. The UMOD gene has emerged as a prominent locus linked to kidney function parameters and CKD risk within the general population. Extensive research in multiple disciplines has underscored the biological significance of the top UMOD gene variants, which have also been associated with hypertension and kidney stones, thus highlighting the diverse and significant impact of uromodulin on kidney-related conditions. UMOD gene mutations are implicated in uromodulin-associated kidney disease, while polymorphisms in the UMOD gene show a significant association with CKD. In conclusion, uromodulin holds great promise as an informative biomarker, providing valuable insights into kidney function and disease progression in various clinical scenarios. The identification of UMOD gene variants further strengthens its relevance as a potential target for better understanding kidney-related pathologies and devising novel therapeutic strategies. Future investigations into the roles of uromodulin and regulatory mechanisms are likely to yield even more profound implications for kidney disease diagnosis, risk assessment, and management.

Prerenal azotemia (PRA) is a major cause of acute kidney injury and uncommonly studied in preclinical models. We sought to develop and characterize a novel model of PRA that meets the clinical definition: acute loss of glomerular filtration rate (GFR) that returns to baseline with resuscitation. Adult male C57BL/6J wild-type (WT) and IL-6-/- mice were studied. Intraperitoneal furosemide (4 mg) or vehicle was administered at time = 0 and 3 h to induce PRA from volume loss. Resuscitation began at 6 h with 1 mL intraperitoneal saline for four times for 36 h. Six hours after furosemide administration, measured glomerular filtration rate was 25% of baseline and returned to baseline after saline resuscitation at 48 h. After 6 h of PRA, plasma interleukin (IL)-6 was significantly increased, kidney and liver histology were normal, kidney and liver lactate were normal, and kidney injury molecule-1 immunofluorescence was negative. There were 327 differentially regulated genes upregulated in the liver, and the acute phase response was the most significantly upregulated pathway; 84 of the upregulated genes (25%) were suppressed in IL-6-/- mice, and the acute phase response was the most significantly suppressed pathway. Significantly upregulated genes and their proteins were also investigated and included serum amyloid A2, serum amyloid A1, lipocalin 2, chemokine (C-X-C motif) ligand 1, and haptoglobin; hepatic gene expression and plasma protein levels were all increased in wild-type PRA and were all reduced in IL-6-/- PRA. This work demonstrates previously unknown systemic effects of PRA that includes IL-6-mediated upregulation of the hepatic acute phase response.NEW & NOTEWORTHY Prerenal azotemia (PRA) accounts for a third of acute kidney injury (AKI) cases yet is rarely studied in preclinical models. We developed a clinically defined murine model of prerenal azotemia characterized by a 75% decrease in measured glomerular filtration rate (GFR), return of measured glomerular filtration rate to baseline with resuscitation, and absent tubular injury. Numerous systemic effects were observed, such as increased plasma interleukin-6 (IL-6) and upregulation of the hepatic acute phase response.

Cardiac surgery may induce acute kidney injury and the need for renal replacement therapy. It is also associated with higher hospital costs, morbidity and mortality. The aims of this study were to investigate predictors of cardiac surgery associated acute kidney injury in our population and to determine the burden of acute kidney injury in elective cardiac surgery, evaluating the potential cost effectiveness of preventing it through the application of the Kidney Disease: Improving Global Outcomes bundle of care to high-risk patient groups identified by the [TIMP-2]x[IGFBP7] used as a screening test.

In a University Hospital single-center retrospective cohort study we analyzed a consecutive sample of adults who underwent elective cardiac surgery between January and March 2015. A total of 276 patients were admitted during the study period. Data from all patients was analyzed until hospital discharge or the patient's death. The economic analysis was performed from the hospital costs' perspective.

Cardiac surgery associated acute kidney injury occurred in 86 patients (31%). After adjustment, higher preoperative serum creatinine (mg/L, ORadj = 1.09; 95% CI: 1.01 - 1.17), lower preoperative hemoglobin (g/dL, ORadj = 0.79; 95% CI: 0.67 - 0.94), chronic systemic hypertension (ORadj = 5.00; 95% CI: 1.67 - 15.02), an increase in cardiopulmonary bypass time (min, ORadj = 1.01; 95% CI: 1.00 - 1.01) and perioperative use of sodium nitroprusside (ORadj = 6.33; 95% CI: 1.80 - 22.28) remained significantly associated with cardiac surgery related acute kidney injury. The expected cumulative surplus cost for the hospital linked with cardiac surgery associated acute kidney injury (86 patients) was €120 695.84. Based on a median absolute risk reduction of 16.6%, by dosing kidney damage biomarkers in every patient and using preventive measures in high-risk patients, we would expect a break-even point upon screening 78 patients, which would translate, in our patient cohort, into an overall cost benefit of €7145.

Preoperative hemoglobin, serum creatinine, systemic hypertension, cardiopulmonary bypass time and perioperative use of sodium nitroprusside were independent predictors of cardiac surgery associated acute kidney injury. Our cost-effectiveness modelling suggests that the use of kidney structural damage biomarkers combined with an early prevention strategy could be associated with potential cost savings.

Open-heart surgery is associated with high morbidity, with acute kidney injury (AKI) being one of the most commonly observed postoperative complications. Following open-heart surgery, in an observational study we found significantly higher numbers of blood neutrophils in a group of 13 patients with AKI compared to 25 patients without AKI (AKI: 12.9±5.4 ×109 cells/L; non-AKI: 10.1±2. 9 ×109 cells/L). Elevated serum levels of neutrophil extracellular trap (NETs) components, such as dsDNA, histone 3, and DNA binding protein Y-box protein (YB)-1, were found within the first 24 hours in patients who later developed AKI. We could demonstrate that NET formation and hypoxia triggered the release of YB-1, which was subsequently shown to act as a mediator of kidney tubular damage. Experimentally, in two models of AKI mimicking kidney hypoperfusion during cardiac surgery (bilateral ischemia/reperfusion (I/R) and systemic lipopolysaccharide (LPS) administration), a neutralizing YB-1 antibody was administered to mice. In both models, prophylactic YB-1 antibody administration significantly reduced the tubular damage (damage score range 1-4, the LPS model: non-specific IgG control, 0.92±0.23; anti-YB-1 0.65±0.18; and in the I/R model: non-specific IgG control 2.42±0.23; anti-YB-1 1.86±0.44). Even in a therapeutic, delayed treatment model, antagonism of YB-1 ameliorated AKI (damage score, non-specific IgG control 3.03±0.31; anti-YB-1 2.58±0.18). Thus, blocking extracellular YB-1 reduced the effects induced by hypoxia and NET formation in the kidney and significantly limited AKI, suggesting that YB-1 is part of the NET formation process and an integral mediator of cross-organ effects.

AKI is a heterogeneous syndrome. Current subphenotyping approaches have only used limited laboratory data to understand a much more complex condition.

We focused on patients with AKI from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI). We used hierarchical clustering with Ward linkage on biomarkers of inflammation, injury, and repair/health. We then evaluated clinical differences between subphenotypes and examined their associations with cardiorenal events and death using Cox proportional hazard models.

We included 748 patients with AKI: 543 (73%) of them had AKI stage 1, 112 (15%) had AKI stage 2, and 93 (12%) had AKI stage 3. The mean age (±SD) was 64 (13) years; 508 (68%) were men; and the median follow-up was 4.7 (Q1: 2.9, Q3: 5.7) years. Patients with AKI subphenotype 1 ( N =181) had the highest kidney injury molecule (KIM-1) and troponin T levels. Subphenotype 2 ( N =250) had the highest levels of uromodulin. AKI subphenotype 3 ( N =159) comprised patients with markedly high pro-brain natriuretic peptide and plasma tumor necrosis factor receptor-1 and -2 and low concentrations of KIM-1 and neutrophil gelatinase-associated lipocalin. Finally, patients with subphenotype 4 ( N =158) predominantly had sepsis-AKI and the highest levels of vascular/kidney inflammation (YKL-40, MCP-1) and injury (neutrophil gelatinase-associated lipocalin, KIM-1). AKI subphenotypes 3 and 4 were independently associated with a higher risk of death compared with subphenotype 2 and had adjusted hazard ratios of 2.9 (95% confidence interval, 1.8 to 4.6) and 1.6 (95% confidence interval, 1.01 to 2.6, P = 0.04), respectively. Subphenotype 3 was also independently associated with a three-fold risk of CKD and cardiovascular events.

We discovered four AKI subphenotypes with differing clinical features and biomarker profiles that are associated with longitudinal clinical outcomes.

In clinical practice, extracorporeal circulation (ECC) is associated with coagulopathy and inflammation, eventually leading to organ injuries without preventive systemic pharmacological treatment. Relevant models are needed to reproduce the pathophysiology observed in humans and preclinical tests. Rodent models are less expensive than large models but require adaptations and validated comparisons to clinics. This study aimed to develop a rat ECC model and to establish its clinical relevance. One hour of veno-arterial ECC or a sham procedure were achieved on mechanically ventilated rats after cannulations with a mean arterial pressure objective > 60 mmHg. Five hours post-surgery, the rats' behavior, plasmatic/blood biomarkers, and hemodynamics were measured. Blood biomarkers and transcriptomic changes were compared in 41 patients undergoing on-pump cardiac surgery. Five hours post-ECC, the rats presented hypotension, hyperlactatemia, and behavioral alterations. The same patterns of marker measurements (Lactate dehydrogenase, Creatinine kinase, ASAT, ALAT, and Troponin T) were observed in both rats and human patients. Transcriptome analyses showed similarity in both humans and rats in the biological processes involved in the ECC response. This new ECC rat model seems to resemble both ECC clinical procedures and the associated pathophysiology, but with early organ injury corresponding to a severe phenotype. Although the mechanisms at stake in the post-ECC pathophysiology of rats or humans need to be described, this new rat model appears to be a relevant and costless preclinical model of human ECC.

Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies.

This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites.

The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.

NCT05126303.

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

This study aimed to develop comprehensive nomograms for patients with head and neck non-Hodgkin lymphoma (H&NNHL) to determine their overall survival (OS) and cancer-specific survival (CSS). In this study, 602 H&NNHL patients were analyzed from the Surveillance, Epidemiology, and End Results database. The R software was used to randomly divide the patients into the training cohort (n = 421) and the validation cohort (n = 181) in a 7-to-3 ratio. To develop nomograms for projecting OS and CSS, multivariable Cox regression was used to acquire independent predictive factors. We have constructed nomograms to predict the 3-, 5-, and 8-year OS and CSS probabilities of H&NNHL patients. The consistency index of the nomograms for OS (CSS) was 0.74 (0.778) and 0.734 (0.775), in the training and validation cohort respectively, and was higher than that of the Ann Arbor staging system. Calibration plotting showed that our models have good calibration ability. Moreover, assessments of the area under the time-dependent receiver operating characteristics curve, net reclassification improvement, integrated discrimination improvement and decision curve analysis demonstrated that our nomograms performed better and were more clinically useful than the Ann Arbor staging system. This is the first research to establish comprehensive nomograms for predicting OS and CSS in patients with H&NNHL at 3-, 5-, and 8-year. The validation of the models demonstrated good performance. It can provide clinicians with reference information for determining customized clinical treatment options and providing personalized prognoses. Indexes such as the concordance index, the area under the time-dependent receiver operating characteristics curve, calibration curves, the net reclassification improvement, the integrated discrimination improvement, and decision-curve analysis were used to compare new survival models to the classical Ann Arbor staging system.

The objective of this study is to determine the prognostic factors of keratinizing squamous cell carcinoma of the tongue (KTSCC) and to establish a prognostic nomogram of KTSCC to assist clinical diagnosis and treatment.

This study identified 3874 patients with KTSCC from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were randomly divided into the training (70%, (n = 2711) and validation (30%, n = 1163) cohorts. Cox regression was then used to filter variables. Nomograms were then constructed based on meaningful variables. Finally, the concordance index (C-index), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration charts, and decision-curve analysis (DCA), were used to evaluate the discrimination, accuracy and effectiveness of the model.

A nomogram model was established for predicting the 3-, 5-, and 8-year overall survival (OS) probabilities of patients with KTSCC. The model indicated that age, radiotherapy sequence, SEER stage, marital status, tumor size, American Joint Committee on Cancer (AJCC) stage, radiotherapy status, race, lymph node dissection status, and sex were factors influencing the OS of patients with KTSCC. Verified by C-index, NRI, IDI, calibration curve, and DCA curve, our model has better discrimination, calibration, accuracy and net benefit compared to the AJCC system.

This study identified the factors that affect the survival of KTSCC patients and established a prognostic nomogram that can help clinicians predict the 3-, 5-, and 8-year survival rates of KTSCC patients.

This study aimed to develop and validate a nomogram for predicting cancer-specific survival (CSS) in patients with non-keratinized large cell squamous cell carcinoma (NKLCSCC) at 3, 5, and 8 years after diagnosis.

Data on SCC patients were collected from the Surveillance, Epidemiology, and End Results database. Training (70%) and validation (30%) cohorts were generated using random selection of patients. Independent prognostic factors were selected using the backward stepwise Cox regression model. To predict the CSS rates in patients with NKLCSCC at 3, 5, and 8 years after diagnosis, all of the factors were incorporated into the nomogram. Indicators such as the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration curve, and decision-curve analysis (DCA) were then used to validate the performance of the nomogram.

This study included 9,811 patients with NKLCSCC. Twelve prognostic factors were identified by Cox regression analysis in the training cohort, which were age, number of regional nodes examined, number of positive regional nodes, sex, race, marital status, American Joint Committee on Cancer (AJCC) stage, surgery status, chemotherapy status, radiotherapy status, summary stage, and income. The constructed nomogram was validated both internally and externally. The nomogram had good discrimination ability, as indicated by the comparatively high C-indices and AUC values. The nomogram was properly calibrated, as indicated by the calibration curves. Our nomogram was superior to the AJCC model, as illustrated by its superior NRI and IDI values. DCA curves indicated the clinical usability of the nomogram.

The first nomogram for prognosis predictions of patients with NKLCSCC has been developed and verified. Its performance and usability demonstrated that the nomogram could be utilized in clinical settings. However, additional external verification is still required.