Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study.

BACKGROUND: Previous observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function. METHOD: We performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test. RESULTS: The findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW ß = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW ß = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10- 6), eGFRcrea with SCF (IVW ß =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10- 8), eGFRcys with GCSF (IVW ß =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW ß =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW ß =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10- 4). CONCLUSIONS: Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.

Self-adhesive, freeze-tolerant, and strong hydrogel electrolyte containing xanthan gum enables the high-performance of zinc-ion hybrid supercapacitors.

Hydrogel electrolyte is an ideal candidate material for flexible energy storage devices due to its excellent softness and conductivity properties. However, challenges such as the inherent mechanical weakness, the susceptibility to be frozen in low-temperature environments, and the insufficiency of hydrogel-electrode contact persist. Herein, a "Multi in One" strategy is employed to effectively conquer these difficulties by endowing hydrogels with high strength, freeze-resistance, and self-adhesive ability. Multiple hydrogen bond networks and ion crosslinking networks are constructed within the hydrogel electrolyte (PVA/PAAc/XG) containing polyvinyl alcohol (PVA), acrylic acid (AAc), and xanthan gum (XG), promoting the enhanced mechanical property, and the adhesion to electrode materials is also improved through abundant active groups. The introduction of zinc ions provides the material with superior frost resistance while also promoting electrical conductivity. Leveraging its multifunction of superior mechanical strength, anti-freeze property, and self-adhesive characteristic, the PVA/PAAc/XG hydrogel electrolyte is employed to fabricate zinc ion hybrid supercapacitors (ZHS). Remarkably, ZHS exhibits outstanding electrochemical performance and cycle stability. A remarkable capacity retention rate of 83.86 % after 10,000 charge-discharge cycles can be achieved at high current densities, even when the operational temperature decreases to -60 °C, showing great potential in the field of flexible energy storage devices.

Serum osmolality was non-linearly associated with the risk of all-cause and cardiovascular mortality in patients with diabetes.

AIMS: This study aimed to evaluate the relationship between both low and high osmolarity and the risk of all-cause and cause-specific mortality in diabetic population. METHODS: All participants were included from the National Health and Nutrition Examination Survey 1999-2014. Baseline serum osmolality was determined from laboratory tests and cause of death from national death records. HRs and 95% CIs for all-cause mortality and cardiovascular mortality in diabetes were estimated using Cox proportional regression analysis. The non-linear relationship was explored using restricted cubic splines regression. RESULTS: Among 7622 individuals with diabetes, 1983 (12.4%) died during a total of 3.26 thousand person-years of follow-up. Compared with the reference category (281-284 mmol/kg), the multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.16-1.40; p<0.001) in the lowest osmolality category (<201 mmol/kg) and 1.18 (1.09-1.28; p<0.001) in the highest osmolality category (>312 mmol/kg). Restricted cubic splines results showed that serum levels of osmolality had a U-shaped association with the risk of all-cause mortality, and L-shaped relationship with the risk of cardiovascular death. CONCLUSIONS: Both low osmolality and high osmolality were predictive of increased all-cause mortality in patients with diabetes, supporting a U-shaped relationship. Also, a lower serum osmolality increased the risk of cardiovascular mortality.

Improved maximum likelihood method for P-S-N curve fitting method with small number specimens and application in T-welded joint.

In fatigue data analysis, fitting accurate P-S-N curve is problematic if only a small number of specimen is available, especially to evaluate the relationship between the stress level and the standard deviation. This paper proposes a sample information reconstruction method that can effectively solve this problem. Based on this method and the life equivalent principle, a new maximum likelihood method (which is abbreviated to improved maximum likelihood method) is proposed for P-S-N curve fitting. T-joint specimens of Q450NQR1 steel were fabricated and tested, then the P-S-N curves was fitted by the improved maximum likelihood method, least square method, maximum likelihood method, standard BS7608 and standard IIW. Finally, P-S-N curves by three methods and two standards are compared and analyzed. The results show that the relevant parameters of the P-S-N curve with 99.9% survival probability fitted by the improved maximum likelihood method are similar to those in the two standards, and it is indicated that the improved maximum likelihood method is a better way for P-S-N curve fitting with the small number of fatigue test specimens.

Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study.

BACKGROUND: Previous observational studies have reported that lifestyle factors, metabolic factors and socioeconomic status are associated with the development of female pelvic organ prolapse (POP); however, whether these associations are causal remains unclear. The current study aimed to assess the causal effect of lifestyle factors, metabolic factors and socioeconomic status on POP risk. METHODS: We conducted a two-sample Mendelian randomization (MR) study based on summary-level data from the largest available genome-wide association studies (GWAS) to evaluate whether lifestyle factors, metabolic factors and socioeconomic status are causally related to POP. We used single nucleotide polymorphisms that are strongly associated with exposure at the genome-wide significance level (P < 5 × 10-8) as instrumental variables from genome-wide association studies. The method of random-effect inverse-variance weighting (IVW) was used as the primary analysis method, supplemented with the weighted median, MR-Egger and the MR pleiotropy residual sum and outlier applied to verify the MR assumptions. Two-step MR was conducted to investigate potential intermediate factors that are on the causal pathway from exposure to POP. RESULTS: There were associations with POP for genetically predicted waist-to-hip ratio (WHR) (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.03 per SD-increase, P < 0.001), WHR adjusted for body mass index (WHRadjBMI) (OR 1.017, 95% CI 1.01-1.025 per SD-increase, P < 0.001) and education attainment (OR 0.986, 95% CI 0.98-0.991 per SD-increase) in the meta-analysis. Additionally, genetically predicted coffee consumption (OR per 50% increase 0.67, 95% CI 0.47-0.96, P = 0.03), vigorous physical activity (OR 0.83, 95% CI 0.69-0.98, P = 0.043) and high-density lipoprotein cholesterol (HDL-C) (OR 0.91, 95% CI 0.84-0.98 per SD-increase, P = 0.049) were inversely associated with POP in the FinnGen Consortium. The mediation analysis showed that the indirect effects of education attainment on POP were partly mediated by WHR and WHRadjBMI, with a mediated proportion of 27% and 13% in the UK Biobank study, respectively. CONCLUSIONS: Our study provides MR evidence of a robust causal association of WHR, WHRadjBMI and education attainment with POP.

The complete chloroplast genome sequence of Zanthoxylum undulatifolium Hemsl. (Rutaceae).

Zanthoxylum undulatifolium is an excellent economic tree species with important medical value. This study reports the first complete chloroplast genome sequence of Z. undulatifolium. Its whole chloroplast genome is 158,400 bp in length, including a large single-copy (LSC) region of 85,898 bp, a small single-copy (SSC) region of 17,610 bp, and two inverted repeat (IR) regions of 27,446 bp. The chloroplast genome contains a total of 132 genes, comprising 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the chloroplast genome is 38.46%, with the corresponding values in the LSC, SSC, and IR regions are 36.87%, 33.51%, and 42.55%, respectively. Phylogenetic analysis revealed the sister relationship between Z. undulatifolium and Z. bungeanum.

Colchicine for Secondary Prevention of Coronary Artery Disease: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Colchicine has become prominent as an anti-inflammatory therapy for secondary cardiovascular prevention in patients with coronary artery disease (CAD). This meta-analysis was performed to evaluate the efficacy and safety of colchicine in patients with CAD. METHODS: Randomised controlled trials (RCTs) that compare major adverse cardiovascular events (MACEs) between patients with CAD randomised to colchicine versus placebo (or no colchicine) were included. Random effect risk ratios (RRs) were calculated for clinical outcomes. RESULTS: A total of 12,071 patients in seven RCTs were included in the meta-analysis. Compared with placebo or no colchicine, colchicine was associated with a significantly lower incidence of MACEs (RR 0.64, 95% CI 0.51-0.80, p<0.01). The reduction in MACEs in the colchicine group was driven by statistically significant reductions in the incidence of myocardial ischaemia (RR 0.74, 95% CI 0.58-0.95, p=0.02), coronary revascularisation (RR 0.61, 95% CI 0.42-0.89, p=0.01), and stroke (RR 0.48, 95% CI 0.28-0.83, p=0.01). However, there was no statistically significant difference for cardiovascular death (RR 0.82, 95% CI 0.55-1.22, p=0.33). All-cause and non-cardiovascular mortality, gastrointestinal events, infection, and cancer were not significantly different between the colchicine and control groups. CONCLUSIONS: Colchicine is a reasonably efficacious and safe drug that could be successfully utilised for the secondary prevention of CAD.

Comparison of two techniques for the management of 2-3 cm lower pole renal calculi in obese patients.

OBJECTIVE: To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. PATIENTS AND METHODS: 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. RESULTS: Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. CONCLUSION: In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.

Circular RNAs in prostate cancer: Biogenesis,biological functions, and clinical significance.

Circular RNAs (circRNAs) are covalently closed RNA molecules that play important regulatory roles in various tumors. Prostate cancer (PCa) is one of the most common malignant tumors in the world, with high morbidity and mortality. In recent years, more and more circRNAs have been found to be abnormally expressed and involved in the occurrence and development of PCa, including cell proliferation, apoptosis, invasion, migration, metastasis, chemotherapy resistance, and radiotherapy resistance. Most of the circRNAs regulate biological behaviors of cancer through a competitive endogenous RNA (ceRNA) regulatory mechanism, and some can exert their functions by binding to proteins. circRNAs are also associated with many clinicopathological features of PCa, including tumor grade, lymph node metastasis, and distant metastasis. In addition, circRNAs are potential diagnostic and prognostic biomarkers for PCa. Considering their critical regulatory roles in the progression of PCa, circRNAs would be the potential therapeutic targets. In this paper, the current research status of circRNAs in PCa is briefly reviewed.

Biological Roles and Clinical Significance of Exosome-Derived Noncoding RNAs in Bladder Cancer.

Bladder cancer (BCa) is a common heterogeneous urinary system tumor with high malignancy and limited advancement in treatment. Limited understanding of BCa has not contributed to any significant progress in diagnosis or treatment, exploring the mechanisms underlying BCa has become an urgent research focus. Exosomes, a type of extracellular vesicle (EV), have drawn substantial interest for their important roles in mediating intracellular communication. Exosomes shuttle numerous bioactive molecules, and noncoding RNAs (ncRNAs) are among the most numerous. ncRNAs including microRNA, long noncoding RNA, and circular RNA are sorted and packaged into exosomes selectively and transferred into recipient cells to regulate their function. Exosomal ncRNAs are associated with hallmarks of BCa, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, lymphangiogenesis, and chemotherapy resistance. Exosomal ncRNAs can also be detected in urine and serum, making them encouraging biomarkers for BCa diagnosis and prognosis. More importantly, exosomes exhibit excellent biocompatibility and potential for diversified applications. The delivery of bioactive substances and drugs into specific cells has become a promising approach for precision therapy for BCa patients. In addition, cancer vaccines have also received increasing attention. In this review, we summarize the current research on the regulatory roles of exosomal ncRNAs in BCa tumorigenesis and progression, as well as their potential clinical value in accelerating the diagnosis and therapy of BCa.

Comparison and development of preoperative systemic inflammation markers-based models for the prediction of unfavorable pathology in newly diagnosed clinical T1 renal cell carcinoma.

BACKGROUND: We sought to investigate the preoperative risk factors associated with the unfavorable pathology (UP) of clinical T1 (cT1) renal lesions. The aims of this study were to develop and compare several novel models capable of accurately identifying those patients at high risk of harboring occult adverse histopathological characteristics. METHODS: The clinical parameters and preoperative laboratory test results from 1281 cT1 renal cell carcinomas (RCCs) patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) were collected. The data was randomly split into training (70%) and testing (30%) datasets. We performed univariable and multivariable logistic regression analyses for significant predictors and, subsequently, constructed predictive models based on those significant risk factors. Receiver operating characteristic (ROC) analysis was used to determine the model with the highest discrimination power with corresponding area under the curve (AUC). Calibration curves were plotted and decision curve analyses (DCAs) were applied to explore clinical net benefit. RESULTS: UP was identified in 21.1% (n = 270), 21.0% (n = 188) and 21.3% (n = 82) patients in the total population, training cohort and validation cohort, respectively. R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to the polar lines) nephrometry score, tumor size, neutrophil-to-lymphocyte ratio (NLR) and albumin-to-globulin ratio (AGR) were independent predictors of UP. Among those predictive models, the model that consisted of tumor size, hemoglobin, NLR and AGR performs best according to the highest AUC of 0.70 and the highest net benefit. When tumor histology was added to the biomarker-based model, including tumor size, hemoglobin, NLR and AGR, the AUC improved from 0.60 to 0.63 in the validation cohort. CONCLUSIONS: In this analytical model study, our findings verified that systemic inflammation response markers showed high potential for identifying UP. Our biomarker-based models well predicted occult aggressive histopathological characteristics among patients with cT1 renal lesions, and the use of models may be greatly beneficial to urologists in tailoring precise management and therapy for patients. Robust validation is warranted prior to adoption into clinical practice.

Added Value of Systemic Inflammation Markers in Predicting Clinical Stage T1 Renal Cell Carcinoma Pathologically Upstaged to T3a.

OBJECTIVES: We aimed to determine preoperative risk factors associated with pathologic T3a (pT3a) upstaging of clinical T1 (cT1) renal cell carcinomas (RCCs) and develop a novel model capable of accurately identifying those patients at high risk of harboring occult pT3a characteristics. METHODS: A retrospective analysis of 1324 cT1 RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) was performed. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with cT1 to pT3a upstaging and subsequently, those significant risk factors were used to construct models. We used the area under the curve (AUC) to determine the model with the highest discrimination power. Decision curve analyses (DCAs) were applied to evaluate clinical net benefit associated with using the predictive models. RESULTS: The rates of upstaging were 6.1% (n = 81), 5.8% (n = 54) and 6.8% (n = 27) in the total population, training cohort and validation cohort, respectively. Tumor size, clinical T stage, R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) nephrometry score, lymphocyte to monocyte ratio (LMR), prognostic nutrition index (PNI) and albumin to globulin ratio (AGR) were significantly associated with pT3a upstaging. The model that consisted of R.E.N.A.L. score, LMR, AGR and PNI achieved the highest AUC of 0.70 in the validation cohort and yielded the highest net benefit. In the subpopulation with complete serum lipid profile, the inclusion of low-density lipoprotein cholesterol (LDL-C) and Castelli risk index-I (CRI-I) significantly improved the discrimination of model (AUC = 0.86). CONCLUSIONS: Our finding highlights the importance of systemic inflammation response markers and serum lipid parameters in predicting pT3a upstaging. Our model had relatively good discrimination in predicting occult pT3a disease among patients with cT1 renal lesions, and the use of the model may be greatly beneficial to urologists in risk stratification and management decisions.

Retroperitoneoscopic nephrectomy versus open surgery for non-tuberculous pyonephrotic nonfunctioning kidney: a single-center experience.

BACKGROUND: Patients with obstructive pyonephrotic nonfunctioning kidney (OPNK) often require simple nephrectomy for long-term severe clinical symptoms. We aimed to analyze the outcomes of retroperitoneal laparoscopy versus open surgery for OPNK. METHODS: The study included clinical data of 69 patients with non-tuberculous OPNK from January 2015 to June 2019 in a single center. The patients were divided into laparoscopic group (LS, N=33) and open surgery group (OS, N=36). Those whose pathological findings were xanthogranulomatous inflammation or tuberculous granuloma were excluded. Statistical analysis compared the two groups in terms of basic demographic characteristics, preoperative laboratory examination results, and intraoperative and postoperative observation indicators. RESULTS: The results showed that non-tuberculous OPNK were more common in women (female/male =4:1). Compared with the LS group, patients in the OS group had higher white blood cells (WBC; P=0.010) and neutrophils (P=0.005) counts before surgery. The main clinical symptoms were low back pain, pyuria, and fever; among them, low back pain combined with pyuria was in the majority. More intraoperative hypotension events were observed in the OS group (P=0.007). Notably, subgroup analysis showed larger stone size happened in the OS group (OR 3.538, 95% CI, 1.337, 9.208). No statistical difference was found in the duration of surgery between the two groups while the length of postoperative hospitalization and retroperitoneal drainage, and postoperative blood transfusion rate increased significantly in the OS group. Postoperative use of non-steroidal anti-inflammatory drugs was more common in the LS group, while opioid analgesics were in the OS group (P=0.0006). There was no statistical difference in other complications. CONCLUSIONS: In conclusion, considering the advantages of LS in terms of postoperative blood transfusion, surgical drainage and length of hospital stay, we recommend it for non-tubercular OPNK when the stone load of pyonephrosis side was less than 280 mm2 and the preoperative WBC and neutrophil count were within the normal range.

Machine learning-assisted decision-support models to better predict patients with calculous pyonephrosis.

BACKGROUND: To develop a machine learning (ML)-assisted model capable of accurately identifying patients with calculous pyonephrosis before making treatment decisions by integrating multiple clinical characteristics. METHODS: We retrospectively collected data from patients with obstructed hydronephrosis who underwent retrograde ureteral stent insertion, percutaneous nephrostomy (PCN), or percutaneous nephrolithotomy (PCNL). The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. We developed 5 ML-assisted models from 22 clinical features using logistic regression (LR), LR optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), support vector machine (SVM), extreme gradient boosting (XGBoost), and random forest (RF). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Decision curve analysis (DCA) was used to investigate the clinical net benefit associated with using the predictive models. RESULTS: A total of 322 patients were included, with 225 patients in the training dataset, and 97 patients in the testing dataset. The XGBoost model showed good discrimination with the AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.981, 0.991, 0.962, 1.000, 1.000, and 0.989, respectively, followed by SVM [AUC =0.985, 95% confidence interval (CI): 0.970-1.000], Lasso-LR (AUC =0.977, 95% CI: 0.958-0.996), LR (AUC =0.936, 95% CI: 0.905-0.968), and RF (AUC =0.920, 95% CI: 0.870-0.970). Validation of the model showed that SVM yielded the highest AUC (0.977, 95% CI: 0.952-1.000), followed by Lasso-LR (AUC =0.959, 95% CI: 0.921-0.997), XGBoost (AUC =0.958, 95% CI: 0.902-1.000), LR (AUC =0.932, 95% CI: 0.878-0.987), and RF (AUC =0.868, 95% CI: 0.779-0.958) in the testing dataset. CONCLUSIONS: Our ML-based models had good discrimination in predicting patients with obstructed hydronephrosis at high risk of harboring pyonephrosis, and the use of these models may be greatly beneficial to urologists in treatment planning, patient selection, and decision-making.

Assessment of Subclinical Deterioration of Right Ventricular Function by Three-Dimensional Speckle Tracking Echocardiography in Breast Cancer Patients Undergoing Anthracycline-Based Chemotherapy.

OBJECTIVE: This study was aimed at assessing the longitudinal strain changes of RV function using three-dimensional speckle tracking echocardiography (3D STE) in breast cancer patients receiving anthracycline chemotherapy. PATIENTS AND METHODS: A total of 95 women with breast cancer receiving epirubicin (360 mg/m2) underwent 3D STE at baseline, the end of chemotherapy and 12 months after chemotherapy. 3D STE assessment included RV ejection fraction (EF), LV global longitudinal strain (GLS), RV GLS, and RV free wall longitudinal strain (RV FWLS). Meanwhile, serum hs-cTnI and NT-proBNP were measured. Chemotherapy-related cardiac dysfunction (CTRCD) was defined as an absolute decrease in 3D LVEF > 10% to a value <50%, while a percent reduction of 3D LV GLS > 15% indicated subclinical CTRCD. RESULTS: Subclinical CTRCD occurred in 10 (10.5%) patients during follow-up. Compared to baseline, the 3D GLS of LV and GLS and FWLS of RV decreased significantly at 12months after chemotherapy (all p<0.01). Variations of 3D RV GLS and RV FWLS had a good discrimination for predicting subclinical CTRCD. The variation of 3D RV FWLS was the only independent predictor of subclinical CTRCD (OR, 1.37; 95% CI, 1.12-2.87; p = 0.028) in multivariate analysis. The cutoff value with -17.5% of 3D RV FWLS variation had a high predictive accuracy for subclinical CTRCD, with an AUC of 0.74, 80.5% sensitivity and 65.8% specificity. The association between 3D RV FWLS and the cumulative dose of anthracyclines was calculated by Spearman's test (r = -0.71, p < 0.001). CONCLUSION: Longitudinal strain analysis by 3D STE allows the identification of subclinical RV dysfunction when conventional indices of RV function are unaffected. 3D RV FWLS was superior to other parameters in early detection of the development of CTRCD in breast cancer patients receiving epirubicin therapy.

Comparison of contrast-enhanced ultrasound versus conventional ultrasound-guided percutaneous nephrolithotomy in patients with nondilated collecting system: a randomized controlled trial.

OBJECTIVE: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. METHODS: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. RESULTS: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05). CONCLUSIONS: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.

Predicting Prostate Cancer Upgrading of Biopsy Gleason Grade Group at Radical Prostatectomy Using Machine Learning-Assisted Decision-Support Models.

OBJECTIVE: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions. METHODS: We retrospectively collected data from prostate cancer (PCa) patients. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF), and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots and decision curve analysis (DCA) were performed to evaluate the calibration and clinical usefulness of each model. RESULTS: A total of 530 PCa patients were included in this study. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730, and 0.695, respectively, followed by SVM (AUC=0.740, 95% confidence interval [CI]=0.690-0.790), LR (AUC=0.725, 95% CI=0.674-0.776) and RF (AUC=0.666, 95% CI=0.618-0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC=0.735, 95% CI=0.656-0.813), followed by SVM (AUC=0.723, 95% CI=0.644-0.802), LR (AUC=0.697, 95% CI=0.615-0.778) and RF (AUC=0.607, 95% CI=0.531-0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. DCA plots demonstrated that the predictive models except RF were clinically useful. CONCLUSION: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.

A novel comprehensive predictive model for obstructive pyonephrosis patients with upper urinary tract stones.

BACKGROUND: Calculous pyonephrosis tended not to be accurately diagnosed before operations. It is mostly confirmed during percutaneous nephrolithotripsy or percutaneous nephrostomy. We aimed to evaluate the risk factors for predicting obstructive pyonephrosis patients with upper urinary tract stones. METHODS: Clinical data of 322 patients with upper urinary tract stones and obstructive hydronephrosis were retrospectively searched and analyzed in our study. The patients were divided into two groups; pyonephrosis and non-pyonephrosis groups. Both disease related factors and infection-associated indicators were analyzed. Univariate and multivariate logistic analyses were performed on preoperative variables. Accordingly, ROC curves were drawn, and a novel comprehensive model was constructed to predict the pyonephrosis. OUTCOMES: Compared to the non-pyonephrosis group, patients in the pyonephrosis group showed statistical differences in sex, urinary tract infection (UTI) within 3 months, stone density, computerized tomography (CT) value of hydronephrosis, serum creatinine, hydronephrosis, contralateral kidney severe hydronephrosis or atrophy, preoperative white blood cells, neutrophils, serum C-reactive protein, urine leukocyte, nitrite, and urine culture revealed statistical difference (P<0.05). Univariate analysis showed that there were significant differences for sex, UTI history, degree of hydronephrosis, contralateral severe hydronephrosis or atrophy, serum creatinine, and CT value of hydronephrosis (P<0.001). Multivariate analysis demonstrated several independent risk factors for pyonephrosis, including degree of hydronephrosis (P=0.02), CT value of hydronephrosis (P=0.001), urine leukocyte (P=0.002), urine culture (P=0.001) and blood neutrophils (P=0.009). Based on these risk factors, we constructed a novel comprehensive model and confirmed it was an effective method to predict pyonephrosis (AUC, 0.970). Bootstrapped calibration curves showed no untoward deviation in both training and validation dataset (mean absolute error of 0.027, 0.036). CONCLUSIONS: Hydronephrosis, CT value of hydronephrosis, blood neutrophils, urine leukocyte, and urine culture were independent risk factors to predict pyonephrosis. The novel comprehensive model was found to be an effective method to predict pyonephrosis and needed to be further confirmed in prospective studies.

Combined multiple clinical characteristics for prediction of discordance in grade and stage in prostate cancer patients undergoing systematic biopsy and radical prostatectomy.

BACKGROUND: The present study aimed to develop three nomograms by incorporating multiple clinical characteristics to identify those prostate cancer (PCa) patients with high probability of incorrect biopsy Gleason grade group (GG) before making treatment decisions. METHODS: We retrospectively collected data from PCa patients who underwent systematic biopsy and radical prostatectomy from January 2015 to December 2019 at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. Univariable and multivariable logistic regression analyses were preformed to identify independent risk factors associated with upgrading, upstaging and downgrading. By incorporating selected clinical parameters with high predictive value, we constructed three nomograms to predict the probability of upgrading, upstaging and downgrading. Discrimination of nomograms was evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Decision curve analysis (DCA) and calibration curves were performed to evaluate calibration and the clinical usefulness of nomograms. Performance of the three nomograms was validated in the testing dataset. RESULTS: There were 585 PCa patients in total enrolled in this study who met the inclusion criteria. Of the 585 patients, the disease of 262 (44.8 %) was upgraded and 68 (11.6 %) was downgraded, and the disease of 67 (11.5 %) was upstaged. With regard to findings of multivariable analyses, patients' age and biopsy GG (GG 2, GG 3, GG 4 versus GG 1) were significantly associated with upgrading. Moreover, maximum diameter of the index lesion (D-max), clinical T stage (cT3a, cT3b versus cT1-2), number of positive cores and total tumor length were significantly associated with upstaging. Furthermore, d-max, %fPSA (> 0.16 versus ≤ 0.16) and biopsy GG (GG 3, GG 4, GG 5 versus GG 2) were independent predictors of downgrading. The three nomograms displayed good calibration in respective calibration plots. ROC analyses showed good discrimination with satisfactory AUC values and DCA plots demonstrated that the upgrading-risk nomogram, upstaging-risk nomogram and downgrading-risk nomogram were all clinically useful. CONCLUSIONS: The upgrading-risk nomogram, upstaging-risk nomogram, and downgrading-risk nomogram were developed and correctly predicted the probability of incorrect Gleason grade group assigned to patients undergoing systematic biopsy.

Added Value of Biparametric MRI and TRUS-Guided Systematic Biopsies to Clinical Parameters in Predicting Adverse Pathology in Prostate Cancer.

OBJECTIVE: To develop novel models for predicting extracapsular extension (EPE), seminal vesicle invasion (SVI), or upgrading in prostate cancer (PCa) patients using clinical parameters, biparametric magnetic resonance imaging (bp-MRI), and transrectal ultrasonography (TRUS)-guided systematic biopsies. PATIENTS AND METHODS: We retrospectively collected data from PCa patients who underwent standard (12-core) systematic biopsy and radical prostatectomy. To develop predictive models, the following variables were included in multivariable logistic regression analyses: total prostate-specific antigen (TPSA), central transition zone volume (CTZV), prostate-specific antigen (PSAD), maximum diameter of the index lesion at bp-MRI, EPE at bp-MRI, SVI at bp-MRI, biopsy Gleason grade group, and number of positive biopsy cores. Three risk calculators were built based on the coefficients of the logit function. The area under the curve (AUC) was applied to determine the models with the highest discrimination. Decision curve analyses (DCAs) were performed to evaluate the net benefit of each risk calculator. RESULTS: A total of 222 patients were included in this study. Overall, 83 (37.4%), 75 (33.8%), and 107 (48.2%) patients had EPE, SVI, and upgrading at final pathology, respectively. The addition of bp-MRI data improved the discrimination of models for predicting SVI (0.807 vs 0.816) and upgrading (0.548 vs 0.625) but not EPE (0.766 vs 0.763). Similarly, models including clinical parameters, bp-MRI data, and information on systematic biopsies achieved the highest AUC in the prediction of EPE (0.842), SVI (0.913), and upgrading (0.794), and the three corresponding risk calculators yielded the highest net benefit. CONCLUSION: We developed three easy-to-use risk calculators for the prediction of adverse pathological features based on patient clinical parameters, bp-MRI data, and information on systematic biopsies. This may be greatly beneficial to urologists in the decision-making process for PCa patients.