Rationale & Objective Secondary hyperparathyroidism (SHPT) is a common health problem among patients on maintenance hemodialysis. SHR6508, an allosteric modulator of calcium-sensing receptor, is developed to reduce parathyroid hormone (PTH) secretion among Chinese hemodialysis patients with SHPT. This study aimed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SHR6508 administered intravenously. Study Design This was a multicenter, randomized, double-blind, placebo-controlled single and multiple ascending dose phase I trial. Setting & Participants This study was conducted at 18 sites in China. Hemodialysis patients who had serum intact PTH (iPTH) of 400−1300 pg/mL and corrected calcium (cCa) of ≥ 8.4mg/dL (2.1 mmol/L) were enrolled. Interventions Patients were randomized in a ratio of 4:1 to receive SHR6508 or placebo by intravenous injection after hemodialysis. Outcomes The primary outcomes are PK parameters and changes in iPTH and cCa. Results The plasma drug exposures (mean maximum plasma concentration, area under the concentration-time curve) increased proportionally with the dose after the administration of SHR6508. iPTH level declined markedly after a single dose of SHR6508 in all cohorts (5-30mg). Following multiple doses of 5-15 mg, the percentage of patients achieving a reduction in iPTH concentration of ≥30% from baseline to Week 2 (25.0%-90.9%) and Week 4 (36.4%-100.0%) in the 5mg, 10mg, and 15mg groups was higher compared to those (12.5% and 14.3%, respectively) observed in the placebo group. Treatment-emergent adverse events occurred in 41 (95.3%) SHR6508-treated patients and in all patients with placebo, most of which were mild and moderate. Limitations This study had a relatively small sample size and short treatment and follow-up period. Conclusions SHR6508 showed promising efficacy and safety in Chinese hemodialysis patients with SHPT. A starting dose at 5 mg for titration was the best dose and will be used in phase II study.
Characterized by renal inflammation and structural damage, lupus nephritis (LN) is a severe and often debilitating complication of systemic lupus erythematosus. The dynamic regulation of RNA processing, stability, and translation by N6-methyladenosine (m6A) modification has been implicated in the pathophysiology of LN. As an m6A reader, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) plays a crucial role in the pathogenesis of various kidney diseases, yet its precise function in LN remains unclear. IGF2BP2 expression was measured in kidney specimens from LN patients and MRL/LPR mice. MRL/lpr mice were administered IGF2BP2 short hairpin RNA adeno-associated viral vectors, followed by evaluation of proteinuria, renal function, and histology. In vitro experiments employed lipopolysaccharide (LPS) stimulation of human kidney tubular epithelial cells (HK-2) to simulate LN inflammatory responses and further investigated the mechanism of IGF2BP2. Molecular interactions were validated via RNA immunoprecipitation and luciferase reporter assays. IGF2BP2 expression is significantly upregulated in LN and positively correlated with proinflammatory factor levels. Knockdown of IGF2BP2 significantly improved renal injury and alleviated renal inflammatory responses in MRL/LPR mice, as well as reduced LPS-induced inflammatory responses in HK-2 cells. Mechanistically, under LN pathological conditions, IGF2BP2 recognized m6A modifications on signal transducer and activator of transcription 1 (STAT1) mRNA and enhanced its stability, leading to the activation of proinflammatory signaling, exacerbation of renal inflammation, and ultimately renal injury. The m6A reader IGF2BP2 promotes proinflammatory signaling in LN by recognizing m6A-modified STAT1 mRNA. Targeting the IGF2BP2-STAT1 axis may represent a potential therapeutic strategy to ameliorate renal inflammatory responses in LN.
Rationale & Objective:Secondary hyperparathyroidism (SHPT) is a common health problem among patients receiving maintenance hemodialysis. SHR6508, an allosteric modulator of calcium-sensing receptors, was developed to reduce parathyroid hormone secretion among Chinese hemodialysis patients with SHPT. This study aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR6508 administered intravenously. Study Design:This was a multicenter, randomized, double-blind, placebo-controlled single and multiple ascending dose phase 1 trial. Setting & Participants:This study was conducted at 18 sites in China. Hemodialysis patients who had serum intact parathyroid hormone (iPTH) concentration 400-1,300 pg/mL and corrected calcium ≥8.4 mg/dL (2.1 mmol/L) were enrolled. Interventions:Patients were randomized in a 4:1 ratio to receive SHR6508 or placebo by intravenous injection after hemodialysis. Outcomes:The primary outcomes were pharmacokinetic parameters and changes in iPTH and corrected calcium concentrations. Results:The plasma drug exposures (mean maximum plasma concentration, area under the concentration-time curve) increased proportionally with the dose after the administration of SHR6508. iPTH level declined markedly after a single dose of SHR6508 in all cohorts (5-30 mg). After multiple doses of 5-15 mg, the percentage of patients achieving a reduction in iPTH concentration ≥30% from baseline to week 2 (25.0%-90.9%) and week 4 (36.4%-100.0%) in the 5, 10, and 15 mg groups was higher than those observed in the placebo group (12.5% and 14.3%, respectively). Treatment-emergent adverse events, which were mostly mild or moderate, occurred in 41 (95.3%) SHR6508-treated patients and in all patients treated with placebo. Limitations:This study had a relatively small sample size and short treatment and follow-up period. Conclusions:SHR6508 showed promising efficacy and safety in Chinese hemodialysis patients with SHPT. A starting dose of 5 mg for titration was the best dose and will be used in the phase 2 study.
Membranous nephropathy (MN) is a major autoimmune cause of adult primary nephrotic syndrome. Its hallmark pathological feature is the deposition of immune complexes on the subepithelial side of the glomerular basement membrane. Although rituximab(RTX), a well-established targeted biologic agent, is widely used and achieves remission in 60–80% of patients with primary membranous nephropathy (PMN), a subset of patients fails to achieve remission after months of follow-up despite a full-course regimen. These non-responders are classified as having RTX-refractory PMN. This study evaluated the efficacy and safety of obinutuzumab (OBZ) in 11 patients with RTX-refractory PMN. Data from patients with complete follow-up records at the Second Affiliated Hospital of Anhui Medical University (January 2023 to July 2025) were analyzed. Patient characteristics and laboratory parameters were documented, and statistical analyses were performed using SPSS 22.0. The results indicated that 10 patients (90.9%) achieved remission following OBZ treatment, comprising 6 (54.5%) with a partial response and 4 (36.4%) with a complete response. The median time to response was 3.5 months (IQR 1.5–7.75). One patient (9.1%) showed no response. Treatment-related adverse events were mild to moderate and occurred in 3 patients (27.3%), with no severe events reported. OBZ demonstrates promising efficacy and a acceptable safety profile in RTX-refractory PMN, although larger prospective studies with longer follow-up are required for confirmation.
Avermectin, a commonly used agricultural pesticide and antiparasitic agent, typically causes acute human toxicity characterized by central nervous system depression and gastrointestinal disturbances. However, its association with thrombotic microangiopathy has not been previously reported. We describe a 60-year-old woman who developed anuria after ingesting 300 mL (15 g) of avermectin. Laboratory investigations demonstrated thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. Renal biopsy revealed thrombotic microangiopathy-like lesions. Thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome were excluded. Markedly elevated plasma levels of the terminal complement complex (C5b-9) confirmed complement activation, supporting the diagnosis of complement-mediated thrombotic microangiopathy. The patient subsequently received complement inhibition therapy with eculizumab during the disease course. Hematologic abnormalities resolved and renal function gradually recovered, allowing discontinuation of dialysis; however, a definitive causal relationship between eculizumab administration and clinical recovery cannot be established. This case suggests that avermectin poisoning may act as a potential trigger of complement-mediated TMA and highlights the importance of considering this in patients with severe pesticide intoxication complicated by unexplained TMA features.
Objective:This study aimed to construct a risk prediction nomogram model of cardiac valve calcification (CVC) in patients undergoing maintenance hemodialysis (MHD) and to verify its evaluation effect. Methods:A total of 398 patients undergoing hemodialysis were randomly divided into a modeling group (n = 274) and a validation group (n = 124). In the modeling group, 92 patients had CVC and 182 did not. Multivariate logistic regression analysis was conducted to determine the risk factors for CVC in patients undergoing hemodialysis. A nomogram prediction model was constructed using R software, and its predictive performance was evaluated in terms of discrimination, calibration, and clinical utility. Results:This study included 398 patients undergoing MHD with a mean age of 51.17 ± 14.09 years, and the prevalence of CVC was 31.66%. Compared with the non-CVC group, patients in the CVC group were older and had a higher proportion of males, longer dialysis duration, higher prevalence of diabetes, and higher levels of total cholesterol, triglycerides, and fat tissue index, while handgrip strength was significantly lower (all P < 0.05). Multivariate logistic regression analysis identified age (OR = 1.052, 95%CI = 1.028-1.077), male sex (OR = 3.164, 95%CI = 1.679-5.962), dialysis duration ≥ 36 months (OR = 2.096, 95%CI = 1.162-3.781), total cholesterol level (OR = 1.582, 95%CI = 1.191-2.101), and fat tissue index (OR = 1.128, 95%CI = 1.046-1.217) as independent risk factors for CVC (all P < 0.05). The area under the receiver operating characteristic curve (AUC) of the nomogram in the modeling group was 0.789, indicating good discriminative ability. The calibration curve demonstrated good agreement between predicted and observed outcomes. In the validation group, the AUC was 0.751, with calibration curve closely aligned with the ideal reference line. Decision curve analysis (DCA) further confirmed the clinical utility of the nomogram. Conclusion:Patients undergoing hemodialysis who are older, male, have a dialysis duration ≥ 36 months, elevated total cholesterol levels, and increased fat tissue index are at higher risk of developing CVC. The nomogram model demonstrated good predictive performance for CVC in patients undergoing hemodialysis and may serve as a practical tool for identifying high-risk individuals in clinical practice.
Coronary artery calcification (CAC) is a major contributor to cardiovascular disease (CVD) in patients undergoing maintenance hemodialysis (MHD). However, its association with body composition and longitudinal changes in body composition remains understudied to date. This study aimed to investigate the associations of body composition and its longitudinal changes with CAC progression in MHD patients. This prospective observational study included 209 Chinese MHD patients. Body composition was measured via bioelectrical impedance analysis, and CAC was assessed using the Agatston scoring system. Data were collected at baseline and 6 months later. The annualized change in CAC score (ΔCACS > 100) was used to define CAC progression. Unadjusted and adjusted binary logistic regression models were employed to evaluate the associations of body composition and its longitudinal changes with CAC progression, with adjustments for various clinical, biochemical, and demographic confounders. Of the 209 patients, 152 (72.73
BACKGROUND:Sagliker syndrome (SS) is a rare yet severe complication of end-stage renal disease that is predominantly observed in patients who have undergone prolonged hemodialysis and develop secondary hyperparathyroidism (SHPT). SS is characterized by progressive craniofacial and maxillofacial bone deformities, such as mandibular widening, increased interdental spacing, and neuropsychiatric symptoms including anxiety, depression, and cognitive dysfunction. These manifestations significantly impair the quality of life of affected individuals. CASE REPORT:We report the case of a 42-year-old woman undergoing regular hemodialysis who was diagnosed with SHPT and SS. The patient was admitted to the hospital with a 3-year history of skeletal deformity. On December 29, 2012, she underwent total parathyroidectomy (PTx) with some parathyroid tissue transplanted to the left forearm. Over 12 years of regular follow-up, we found that clinical symptoms, such as facial deformity and bone pain, and laboratory indicators, including corrected serum calcium and phosphorus levels, significantly improved. Amazingly, the skull, which was altered in a "salt and pepper" pattern, improved significantly. CONCLUSION:After PTx in patients with SS, clinical symptoms and related laboratory indicators can be significantly improved, which is conducive to enhancing patient prognosis. Therefore, PTx should be performed in such patients as early as possible. However, further research is needed to develop a more standardized treatment plan for SS.
[This corrects the article DOI: 10.3389/fnut.2024.1400726.].
AbstractBackground: Sex-specific associations between exercise behaviors and abdominal obesity remain inconsistent, and the effects of distinct exercise dimensions by sex are unclear in underrecognized normal-BMI older adults with "hidden obesity". We examined sex differences and effect modification by sex in these associations among community-dwelling older adults with normal BMI.Methods: This cross-sectional study used data from a community-based health examination program conducted in Hefei, Anhui, China, between February and November 2025. Eligible participants were aged ≥60 years with normal BMI (18.5–23.9 kg/m²). Abdominal obesity was defined per the 2024 Chinese Dietary Guidelines for Adult Obesity: waist circumference ≥85 cm in men and ≥80 cm in women. Exercise behaviors (frequency, duration per session, type) were assessed via face-to-face structured interviews using a validated Chinese Leisure Time Physical Activity Questionnaire. Multivariable logistic regression adjusted for age, sex, BMI, smoking, alcohol drinking, hypertension, and diabetes was used to examine associations, with sex-stratified analyses and interaction tests.Results: In the fully adjusted model, longer per-session exercise duration (>30 vs 10–30 min) was associated with lower abdominal obesity odds overall (OR=0.67, 95%CI 0.47–0.95, P=0.024). This protective effect was restricted to women (OR=0.40, 95%CI 0.25–0.65, P<0.001), with no significance in men (OR=1.18, 95%CI 0.70–2.00, P=0.532). Higher frequency (≥2 vs <1 time/week) correlated with elevated odds only in women (OR=3.55, 95%CI 1.65–7.84, P=0.001). Exercise type showed no association in either sex, with a significant sex–duration interaction (P=0.011 for interaction).Conclusions: Exercise-abdominal obesity associations are sex-specific in normal-BMI older adults, with longer per-session duration protective but higher frequency risky in women.
IntroductionSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and immune complex-mediated organ damage, frequently involving the kidneys as lupus nephritis (LN). However, reliable blood-based biomarkers for disease activity and renal involvement remain limited.MethodsWe performed serum proteomic profiling in newly diagnosed SLE patients and integrated these data with renal transcriptomic datasets from SLE mouse models to identify candidate biomarkers. Associations between serum RNASE1 levels and clinical parameters were evaluated, and a composite RNASE1-albumin-calcium (RAC) score was developed.ResultsRNASE1 was consistently upregulated in both serum and renal tissues of SLE patients. Serum RNASE1 levels were significantly elevated compared with healthy controls and showed positive correlations with proteinuria and SLE Disease Activity Index (SLEDAI) scores, and a negative correlation with complement C3. The RAC score demonstrated stronger correlations with disease activity and renal function than RNASE1 alone. Receiver operating characteristic (ROC) analysis showed that the RAC score discriminated SLE disease activity with area under the curve (AUC) values of 0.7654, 0.7737, and 0.8072 for ≥mild, ≥moderate, and ≥severe activity, respectively. In addition, renal RNASE1 expression increased with LN severity and was significantly higher in class IV ± V LN than in class III ± V or class V LN, correlating with the pathological activity index.DiscussionRNASE1 is a promising biomarker reflecting both systemic disease activity and renal involvement in SLE. The RNASE1-based RAC score provides a noninvasive tool for improved disease assessment and may facilitate clinical monitoring and management of SLE patients.
This cohort study examines the association between circadian syndrome (CircS) and the risks of all-cause and cardiovascular disease (CVD) mortality, focusing on various age groups. The analysis included 8,972 participants from the National Health and Nutrition Examination Survey (NHANES). Kaplan-Meier survival curves were employed to assess survival probabilities and Cox proportional hazards models were utilized to evaluate the impact of CircS on mortality. The findings revealed a CircS prevalence of 37.7
Abstract Tea is the world’s second most consumed beverage, yet comprehensive global data on intake patterns remain limited. Using individual-level dietary data from the Global Dietary Database 2018, encompassing 1224 surveys across 185 countries, we assessed tea intake among adults aged ≥20 years from 1990 to 2018, stratified by age, sex, education, and urbanicity. In 2018, estimated global mean intake was 6.18 cups/week (95% uncertainty interval: 5.66–6.82), with threefold regional variation ranging from 3.85 cups/week in Latin America and the Caribbean to 8.95 in the Middle East and North Africa. The highest national intakes were in Iran (17.46 cups/week), Japan (14.95), and Afghanistan (13.74). Intake increased modestly with age but showed minimal differences by sex, education, or urbanicity. Globally, estimated intake rose from 1990 to 2018 (estimated annual percentage change [EAPC]: 0.94%), with the largest regional increase in Southeast and East Asia (EAPC: 1.68%), driven primarily by China (EAPC: 3.04%), while traditionally high-consuming countries such as Georgia showed declining trends (EAPC: −5.91%). These findings highlight substantial global heterogeneity in tea consumption and provide a foundation for nutritional surveillance worldwide.
Uric Acid (UA), a weak acid and the final metabolite of purine degradation, exists in two primary forms in vivo: soluble UA (sUA) and Monosodium Urate (MSU) crystals. It is predominantly excreted through urine after the catabolism of adenine and guanine, maintaining a dynamic equilibrium within physiological conditions. UA exhibits notable antioxidant properties that contribute to the maintenance of redox homeostasis and the modulation of immune responses. However, disruptions caused by diet, lifestyle, or metabolic abnormalities can disturb UA equilibrium, resulting in oxidative imbalance, immune dysregulation, and chronic inflammation. Autoimmune Diseases (ADs) arise from a breakdown of immune tolerance, leading to the activation of autoreactive T and B cells, excessive autoantibody formation, dysregulated cytokine networks, and sustained tissue-damaging inflammation. Emerging evidence has unveiled that UA may trigger and participate in the onset and progression of several types of ADs by initiating oxidative stress (OS), modulating immune responses, and amplifying inflammatory mediators. In this review, summarize current advances in understanding the immunological roles of UA in the initiation and progression of ADs. We also evaluate the clinical relevance of UA as an immunomodulatory biomarker and therapeutic target. Furthermore, we explore conventional therapeutic approaches for ADs in combination with UA-lowering interventions, aiming to identify optimized treatment strategies tailored to specific autoimmune conditions to improve clinical outcomes.
Introduction:Sagliker syndrome (SS) is a severe, disfiguring manifestation of refractory secondary hyperparathyroidism (SHPT). Although parathyroidectomy (PTX) corrects biochemical abnormalities, long-term outcomes after PTX in patients with SS remain uncertain. This study hypothesized that SS represents a high-risk phenotype associated with adverse long-term outcomes despite surgical intervention. Methods:This single-center retrospective cohort study included 740 dialysis patients with severe refractory SHPT who underwent PTX. The patients were classified into SS (n = 70) and non-SS (n = 670) groups. Multivariable logistic regression was used to identify factors associated with SS; Cox models were used to evaluate associations of SS with all-cause and cardiovascular disease (CVD) mortality. Sensitivity and subgroup analyses were used to assess robustness. Results:The prevalence of SS was 9.5%. Independent factors associated with SS included longer dialysis vintage (odds ratio [OR] = 1.21, P < 0.001), alkaline phosphatase (ALP) > 315 U/L (OR = 4.14, P < 0.001), hypoalbuminemia (OR = 0.92, P = 0.013), cardiac valve calcification (OR = 2.11, P = 0.014), and abdominal aortic calcification (OR = 2.14, P = 0.016). Exploratory cephalometry in a small subset was consistent with previous SS reports. Exploratory post-PTX analyses suggested improved quality of life (QOL; n = 25), reduced bone pain (n = 45), and stabilization of height loss (n = 15) in patients with SS (all P < 0.05). Over a median follow-up of 81 months, SS was independently associated with higher all-cause mortality (hazard ratio [HR] = 1.71, 95% confidence interval [CI]: 1.01-2.89; P = 0.045) and CVD mortality (HR = 2.44, 95% CI: 1.17-5.06; P = 0.018) after PTX. Conclusion:In this PTX-treated cohort, SS was associated with longer dialysis vintage, high bone turnover, and vascular calcification. Although PTX may provide symptomatic benefit, SS remained associated with higher long-term mortality after PTX and may reflect irreversible systemic damage.
BACKGROUND AND AIM:The aggregate index of systemic inflammation (AISI), a novel inflammatory biomarker, is associated with various diseases. However, its association with cardiovascular risk in patients treated with peritoneal dialysis (PD) remains unclear. This study aims to explore the relationship between AISI and cardiovascular risk in this high-risk population, providing new insights for risk stratification and guiding clinical decision-making. METHODS AND RESULTS:This retrospective study enrolled 316 patients who underwent PD catheter insertion at the Second Affiliated Hospital of Anhui Medical University between January 1, 2010, and July 31, 2022. The optimal cut-off value of AISI for predicting cardiovascular events (CVE) was 213.58 using ROC curve analysis. Based on this cut-off value, patients were classified into high and low AISI groups. During a median follow-up of 39 (22, 66) months, 110 patients (34.8 %) developed CVE, and 37 patients (11.7 %) experienced cardiovascular mortality. Kaplan-Meier curves showed that the cumulative incidence of CVE (P < 0.001) and cardiovascular mortality (P = 0.002) were significantly higher in the high AISI group. After adjusting for potential confounding factors, a higher AISI remained an independent risk factor for both CVE (hazard ratio: 2.052; 95 % CI: 1.330-3.164; P = 0.001) and cardiovascular mortality (hazard ratio: 2.651; 95 % CI: 1.088-6.455; P = 0.032) in patients treated with PD. Subgroup analyses showed no significant interactions between AISI and the subgroup variables (P for interaction >0.05). CONCLUSIONS:Elevated AISI levels are independently associated with an increased risk of CVE and cardiovascular mortality in patients treated with PD. AISI may have significant implications for clinical practice.
INTRODUCTION:Previous studies found that frailty was an important risk factor for cardiovascular disease (CVD). However, the relationship between frailty and CVD risk across different cardiovascular-kidney-metabolic (CKM) syndrome stages remains poorly understood. This study investigated the association between frailty and incident CVD in populations with CKM syndrome stages 0-3. METHODS:We analyzed 6,049 middle-aged and older adults without pre-existing CVD data from the China Health and Retirement Longitudinal Study (2011-2020). Participants were categorized into CKM syndrome stages 0-3 based on the American Heart Association's criteria. Frailty was assessed using the frailty index (FI) and classified as robust, pre-frail, or frail. Cox proportional hazard models examined the association between frailty and incident CVD. RESULTS:During a median follow-up of 7.5 years, 1,441 participants developed CVD. Compared to robust individuals, pre-frail and frail participants had multivariable-adjusted hazard ratios of 1.58 and 2.13 for incident CVD, respectively. Each standard deviation increase in FI was associated with a 28% higher risk of incident CVD. A dose-response relationship was observed between FI and CVD risk, with no significant nonlinearity was detected. These associations remained consistent across all CKM syndrome stages, although significant effect modifications were observed by age, gender, and hypertension status. Sensitivity analyses yielded consistent results. CONCLUSIONS:Frailty is independently associated with increased CVD risk across the spectrum of CKM syndrome stages, with a clear dose-response relationship.
BACKGROUNDS:The association between chromatin accessibility in CD4+ T cells and Immunoglobulin A nephropathy (IgAN) remains unclear. METHODS:We performed the assay for transposase accessible chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq) on CD4+ T cells. ATAC-seq and RNA-seq were conducted to identify differentially accessible regions and differentially expressed genes (DEGs), respectively (P < 0.05, |log2 Fold Change| >1). QRT-PCR was utilized to validate target gene expression. RESULTS:We identified 100,865 differentially accessible regions, of which 7225 exhibited higher accessibility in IgAN. Functional analysis revealed that these regions are enriched in T lymphocyte activation and immune pathways. ELF3, MEIS1, and NFYC were identified as key TFs associated with IgAN. QRT-PCR indicated a significant upregulation of hub genes including MEIS1 in IgAN. CONCLUSION:We identified key TFs and genes by integrating ATAC-seq and RNA-seq, which provide novel therapeutic targets for IgAN and insights into its pathogenesis from an epigenetic perspective.
To compare the performance of predictive models for cardiovascular event (CVE) in patients undergoing peritoneal dialysis (PD) based on machine learning algorithm and Cox proportional hazard regression. This study included patients underwent PD catheterization in our center from January 1, 2010, to July 31, 2022. The patients were randomly divided into training and validation sets in a 7:3 ratio. Cox regression, extreme gradient boosting (XGBoost), and random survival forest (RSF) models were developed using the training set and validated using the validation set. The time-dependent area under the curve (AUC) and concordance index (C-index) were used to evaluate the discriminative ability of predictive models. A total of 318 patients were enrolled in this study. 110 (34.6