Integrating shear wave elastography and estimated glomerular filtration rate to enhance diagnostic strategy for renal fibrosis assessment in chronic kidney disease.

Background: Assessing renal fibrosis non-invasively in patients with chronic kidney disease (CKD) remains a considerable clinical challenge. This study aimed to investigate the diagnostic efficacy of different approaches that combine shear wave elastography (SWE) and estimated glomerular filtration rate (eGFR) in distinguishing between mild fibrosis and moderate-to-severe fibrosis in CKD patients. Methods: In this prospective study, 162 patients underwent renal SWE examinations and renal biopsies. Using SWE, the right renal cortex stiffness was measured, and the corresponding SWE value was recorded. Four diagnostic patterns were used to combine eGFR and SWE value: in isolation, in series, in parallel, and in integration. The receiver operating characteristic (ROC) curve was established, and the area under the ROC curve (AUC) was calculated to quantify diagnostic performance. Sensitivity, specificity, and accuracy were computed. Results: The eGFR demonstrated sensitivity of 68.2% and specificity of 83.8%, whereas the SWE value displayed sensitivity of 84.1% and specificity of 62.2%, yielding a similar AUC (78.2% and 77.8%, respectively). Combining in series improved specificity to 97.3%, superior to other diagnostic patterns (all P values <0.01), but compromised sensitivity to 58.0%. When combined in parallel, the sensitivity increased to 94.3%, exceeding any other strategies (all P values <0.05), but the specificity dropped to 48.7%. The integrated strategy, incorporating eGFR with SWE value via the logistic regression algorithm, exhibited an AUC of 85.8%, outperforming all existing approaches (all P values <0.01), with balanced sensitivity, specificity, and accuracy of 86.4%, 74.3%, and 80.9%, respectively. Conclusions: Using an integrated strategy to combine eGFR and SWE value could improve diagnostic performance in distinguishing between mild renal fibrosis and moderate-to-severe renal fibrosis in patients with CKD, thereby helping clinicians perform a more accurate clinical diagnosis.

Association of renal elasticity evaluated by real-time shear wave elastography with renal fibrosis in patients with chronic kidney disease.

OBJECTIVE: Renal fibrosis is a final common pathological hallmark in the progression of chronic kidney disease (CKD). Non-invasive evaluation of renal fibrosis by mapping renal stiffness obtained by shear wave elastography (SWE) may facilitate the clinical therapeutic regimen for CKD patients. METHODS: A cohort of 162 patients diagnosed with CKD, who underwent renal biopsy, was prospectively and consecutively recruited between April 2019 and December 2021. The assessment of renal cortex stiffness was performed using SWE imaging. The patients were classified into different groups based on pathological renal fibrosis (mild group: n = 74; moderate-to-severe group: n = 88). Binary logistic regression model and generalized additive model were conducted to investigate the association of renal elasticity with renal fibrosis. RESULTS: Compared with the mildly impaired group, the moderate-to-severe group showed a significant decline in renal elasticity (P < .001). In the fully adjusted model, each 10 kPa drop in renal elasticity was associated with a 3.5-fold increment in the risk of moderate-to-severe renal fibrosis (fully adjusted odds ratio, 4.54; 95% CI, 2.41-8.57). Particularly, participants in the lowest elasticity group (≤29.92 kPa) had a 20-fold increased chance of moderate-to-severe renal fibrosis than those in the group with highest elasticity (≥37.93 kPa). An inverse linear association was observed between renal elasticity increment and moderate-to-severe renal fibrosis risk. CONCLUSION: There is a negative linear association between increased renal elasticity and moderate-to-severe renal fibrosis risk among CKD patients. Patients with diminished renal stiffness have a higher risk of moderate-to-severe renal fibrosis. ADVANCES IN KNOWLEDGE: CKD patients with reduced renal stiffness have a higher likelihood of moderate-to-severe renal fibrosis.

Nomogram Analysis Based on Clinical and Sonographic Characteristics for the Assessment of Postpartum Stress Urinary Incontinence.

OBJECTIVES: We aimed to develop and validate a nomogram integrating clinical and sonographic characteristics for the individualized SUI risk evaluation in the early postpartum stage. METHODS: This was a prospective cross-sectional study. From June 2020 to September 2022, singleton primiparas who underwent TPUS examination at 6-8 weeks postpartum were recruited. They were divided into the training and validation cohorts at a ratio of 8:2 according to the temporal split. All subjects were interviewed before TPUS examination. Univariate and multivariate logistic analyses were performed to develop three models: the clinical, sonographic, and combined models. The ROC curve was plotted to evaluate model discrimination ability. Finally, the combined model was selected to establish the nomogram. The nomogram's discrimination, calibration, and clinical usefulness were evaluated in the training and validation cohorts. RESULTS: The performance of the combined model was better than that of the clinical and sonographic models. Six predictors (BMI, delivery mode, lateral episiotomy, SUI during pregnancy, cystocele, and bladder neck funneling) remained in the combined model. The nomogram based on the combined model had good discrimination with AUCs of 0.848 (95% CI: 0.796-0.900) and 0.872 (95% CI: 0.789-0.955) in the training and validation cohorts, respectively, and the calibration curve showed good efficiency in assessing postpartum SUI. Decision curve analysis showed that the nomogram was clinically useful. CONCLUSIONS: The nomogram based on clinical and sonographic characteristics showed good efficiency in assessing postpartum SUI risk and can be a convenient and reliable tool for individual SUI risk assessment.

Ultrasound-based radiomics analysis in the assessment of renal fibrosis in patients with chronic kidney disease.

PURPOSE: Assessment of renal fibrosis non-invasively in chronic kidney disease (CKD) patients is still a clinical challenge. In this study, we aimed to establish a radiomics model integrating radiomics features derived from ultrasound (US) images with clinical characteristics for the assessment of renal fibrosis severity in CKD patients. METHODS: A total of 160 patients with CKD who underwent kidney biopsy and renal US examination were prospectively enrolled. Patients were classified into the mild or moderate-severe fibrosis group based on pathology results. Radiomics features were extracted from the US images, and a radiomics signature was constructed using the maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithms. Multivariable logistic regression was employed to construct the radiomics model, which incorporated the radiomics signature and the selected clinical variables. The established model was evaluated for discrimination, calibration, and clinical utility in the derivation cohort and internal cross-validation (CV) analysis, respectively. RESULTS: The radiomics signature, consisting of nine identified fibrosis-related features, achieved moderate discriminatory ability with an area under the receiver operating characteristic curve (AUC) of 0.72 (95% confidence interval (CI) 0.64-0.79). By combining the radiomics signature with significant clinical risk factors, the radiomics model showed satisfactory discrimination performance, yielding an AUC of 0.85 (95% CI 0.79-0.91) in the derivation cohort and a mean AUC of 0.84 (95% CI 0.77-0.92) in the internal CV analysis. It also demonstrated fine accuracy via the calibration curve. Furthermore, the decision curve analysis indicated that the model was clinically useful. CONCLUSION: The proposed radiomics model showed favorable performance in determining the individualized risk of moderate-severe renal fibrosis in patients with CKD, which may facilitate more effective clinical decision-making.

Using elastography-based multilayer perceptron model to evaluate renal fibrosis in chronic kidney disease.

BACKGROUND: Given its progressive deterioration in the clinical course, noninvasive assessment and risk stratification for the severity of renal fibrosis in chronic kidney disease (CKD) are required. We aimed to develop and validate an end-to-end multilayer perceptron (MLP) model for assessing renal fibrosis in CKD patients based on real-time two-dimensional shear wave elastography (2D-SWE) and clinical variables. METHODS: From April 2019 to December 2021, a total of 162 patients with CKD who underwent a kidney biopsy and 2D-SWE examination were included in this single-center, cross-sectional, and prospective clinical study. 2D-SWE was performed to measure the right renal cortex stiffness, and the corresponding elastic values were recorded. Patients were categorized into two groups according to their histopathological results: mild and moderate-severe renal fibrosis. The patients were randomly divided into a training cohort (n = 114) or a test cohort (n = 48). The MLP classifier using a machine learning algorithm was used to construct a diagnostic model incorporating elastic values with clinical features. Discrimination, calibration, and clinical utility were used to appraise the performance of the established MLP model in the training and test sets, respectively. RESULTS: The developed MLP model demonstrated good calibration and discrimination in both the training [area under the receiver operating characteristic curve (AUC) = 0.93; 95% confidence interval (CI) = 0.88 to 0.98] and test cohorts [AUC = 0.86; 95% CI = 0.75 to 0.97]. A decision curve analysis and a clinical impact curve also showed that the MLP model had a positive clinical impact and relatively few negative effects. CONCLUSIONS: The proposed MLP model exhibited the satisfactory performance in identifying the individualized risk of moderate-severe renal fibrosis in patients with CKD, which is potentially helpful for clinical management and treatment decision-making.

Assessment of Renal Fibrosis in Patients With Chronic Kidney Disease Using Shear Wave Elastography and Clinical Features: A Random Forest Approach.

OBJECTIVE: Renal fibrosis is the common pathological hallmark of chronic kidney disease (CKD) progression. In this study, a random forest (RF) classifier based on 2-D shear wave elastography (SWE) and clinical features for the differential severity of renal fibrosis in patients with CKD is proposed. METHODS: A total of 162 patients diagnosed with CKD who underwent 2-D SWE and renal biopsy were prospectively enrolled from April 2019 to December 2021 and then randomized into training (n = 114) and validation (n = 48) cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression and recursive feature elimination for support vector machines (SVM-RFE) algorithm were employed to select renal fibrosis-related features from clinical information and elastosonographic findings. An RF model was subsequently constructed using the aforementioned informative parameters in the training cohort and evaluated in terms of discrimination, calibration and clinical utility in both cohorts. RESULTS: The LASSO and SVM-RFE analyses revealed that age, sex, blood urea nitrogen, renal resistive index, hypertension and the 2D-SWE value were independent risk variables associated with renal fibrosis severity. The established RF model incorporating these six variables exhibited fine discrimination in both the derivation (area under the curve [AUC]: 0.84, 95% confidence interval [CI]: 0.76-0.91) and validation (AUC: 0.88, 95% CI: 0.77-0.98) cohorts. Moreover, the calibration curve revealed satisfactory predictive accuracy, and the decision curve analysis revealed a significant clinical net benefit. CONCLUSION: The developed RF model, via a combination of the 2-D SWE value and clinical information, indicated satisfactory diagnostic performance and clinical practicality toward differentiating moderate-severe from mild renal fibrosis, which may provide critical insight into risk stratification for patients with CKD.

Exceptional Electron-Rich Heteroaromatic Pentacycle for Ultralow Band Gap Conjugated Polymers and Photothermal Therapy.

Stable redox-active conjugated molecules with exceptional electron-donating abilities are key components for the design and synthesis of ultralow band gap conjugated polymers. While hallmark electron-rich examples such as pentacene derivatives have been thoroughly explored, their poor air stability has hampered their broad incorporation into conjugated polymers for practical applications. Herein, we describe the synthesis of the electron-rich, fused pentacyclic pyrazino[2,3-b:5,6-b']diindolizine (PDIz) motif and detail its optical and redox behavior. The PDIz ring system exhibits a lower oxidation potential and a reduced optical band gap than the isoelectronic pentacene while retaining greater air stability in both solution and the solid state. The enhanced stability and electron density, together with readily installed solubilizing groups and polymerization handles, allow for the use of the PDIz motif in the synthesis of a series of conjugated polymers with band gaps as small as 0.71 eV. The tunable absorbance throughout the biologically relevant near-infrared I and II regions enables the use of these PDIz-based polymers as efficient photothermal therapeutic reagents for laser ablation of cancer cells.

A nomogram based on shear wave elastography for assessment of renal fibrosis in patients with chronic kidney disease.

BACKGROUND: Non-invasive evaluation of renal fibrosis is still challenging. This study aimed to establish a nomogram based on shear wave elastography (SWE) and clinical features for the assessment of the severity of renal fibrosis in patients with chronic kidney disease (CKD). METHODS: One hundred and sixty-two patients with CKD who underwent kidney biopsy and SWE examination were prospectively enrolled between April 2019 and December 2021. Patients were classified into mildly or moderately-severely impaired group based on pathology results. All patients were randomly divided into a training (n = 113) or validation cohort (n = 49). Least absolute shrinkage and selection operator (LASSO) algorithm was used for data dimensionality reduction and feature selection. Then, a diagnostic nomogram incorporating the selected features was constructed using multivariable logistic regression analysis. Nomogram performance was evaluated for discrimination, calibration, and clinical utility in training and validation cohorts. RESULTS: The established SWE nomogram, which integrated SWE value, hypertension, and estimated glomerular filtration rate, showed fine calibration and discrimination in both training (area under the receiver operator characteristic curve (AUC) = 0.94; 95% confidence interval (CI) 0.89-0.98) and validation cohorts (AUC = 0.84; 95% CI 0.71-0.96). Significant improvement in net reclassification and integrated discrimination indicated that the SWE value is a valuable biomarker to assess moderate-severe renal impairment. Furthermore, decision curve analysis revealed that the SWE nomogram has clinical value. CONCLUSION: The proposed SWE nomogram showed favorable performance in determining individualized risk of moderate-severe renal pathological impairment in patients with CKD, which will help to facilitate clinical decision-making.

Estrogen Suppresses Cytokines Release in cc4821 Neisseria meningitidis Infection via TLR4 and ERß-p38-MAPK Pathway.

Estrogen has long been known to possess immune-modulatory effects in diseases, and multiple pathological conditions show great sex disparities. However, the impact of estrogen in Neisseria meningitidis infection has not been determined. The present study aimed to investigate the role of estrogen in N. meningitidis infection and the molecular mechanism. We selected 35 N. meningitidis isolates representing different clonal complexes (cc), serogroups, and isolation sources to infect the HBMEC cell line. Results showed that the expression of estrogen receptor (ER) ß in N. meningitidis-infected cells was downregulated compared with that in normal cells. The expression of ERß induced by invasive isolates was lower than that in carriers. Serogroup C isolates induced the lowest expression of ERß compared with serogroup A and B isolates. We used four cc4821 N. meningitidis isolates to infect two kinds of host cells (human brain microvascular endothelial cells and meningeal epithelial cells). The results showed that 17 ß-estradiol (E2) could inhibit the release of inflammatory factors interleukin (IL)-6, IL-8, and tumor necrosis factor-α after N. meningitidis infection via TLR4. E2 could inhibit the activation of the p38-MAPK signal pathway induced by N. meningitidis infection through binding to ERß, and significantly inhibit the release of inflammatory factors in N. meningitidis-infected host cells. This study demonstrated that estrogen plays a protective role in N. meningitidis infection. ERß is potentially associated with the release of inflammatory cytokines in N. meningitidis infection, which sheds light on a possible therapeutic strategy for the treatment of invasive diseases caused by N. meningitidis.

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression.

BACKGROUND: Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. RESULTS: Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial-mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. CONCLUSIONS: This work provides a new paradigm for the treatment of residual HCC after IRFA.

Evaluation of renal fibrosis in patients with chronic kidney disease by shear wave elastography: a comparative analysis with pathological findings.

PURPOSE: To explore the elastic values obtained by shear wave elastography (SWE) in assessing renal fibrosis in chronic kidney disease (CKD). METHODS: One hundred and twenty-four patients with CKD who underwent renal biopsy were prospectively enrolled between April 2019 and June 2021. SWE was performed to measure the renal cortex stiffness, presented as SWE parameters, including the minimum, mean, and maximum elasticity (namely Emin, Emean, and Emax). Then, the patients with different kidney pathological impairment (mild, moderate, and severe groups) were compared in SWE elasticity and the discriminative capacity was also analyzed. RESULTS: For the pathology impaired grade, SWE parameter was significantly reduced in the moderately and severely impaired group than the mild one. Emax parameter achieved the best discriminative ability toward differentiating moderate-severe impairment from mild one, yielding an area under the curve (AUC) of 0.764 (95%CI: 0.681-0.848). Regarding interstitial fibrosis/tubular atrophy and global glomerular sclerosis, the Emax values were significantly reduced across the group of patients with moderate grade compared to those with mild grade. Patients in severe group were also with reduced elastic value than those in mild one, while the difference was non-significant in interstitial fibrosis/tubular atrophy but a borderline statistical significance was achieved in global glomerular sclerosis. For grade of vessel wall thickening, patients in moderate (33.04 ± 9.86 kPa, P = 0.009) and severe (31.42 ± 9.16 kPa, P < 0.001) group were with significantly lower elastic value compared with those in the mild one (39.58 ± 9.67 kPa). The SWE parameter was linearly reduced as grade of vessel wall thickening elevated (P for trend: < 0.001). CONCLUSION: SWE derived elastic values reduced as pathology grade of renal fibrosis or grade of vessel wall thickening progresses in patients with CKD, which may be attributed to renal hypo-perfusion rather than tubulo-interstitial fibrosis progression.

Operator Radiation and the Efficacy of Ceiling-Suspended Lead Screen Shielding during Coronary Angiography: An Anthropomorphic Phantom Study Using Real-Time Dosimeters.

Operator radiation and the radiation protection efficacy of a ceiling-suspended lead screen were assessed during coronary angiography (CA) in a catheterization laboratory. An anthropomorphic phantom was placed under the X-ray beam to simulate patient attenuation in eight CA projections. Using real-time dosimeters, radiation dose rates were measured on models mimicking a primary operator (PO) and an assistant. Subsequently, a ceiling-suspended lead screen was placed in three commonly used positions to compare the radiation protection efficacy. The radiation exposure to the PO was 2.3 to 227.9 (mean: 67.2 ± 49.0) µSv/min, with the left anterior oblique (LAO) 45°/cranial 25° and cranial 25° projections causing the highest and the lowest dose rates, respectively. The assistant experienced significantly less radiation overall (mean: 20.1 ± 19.6 µSv/min, P < 0.003), with the right anterior oblique (RAO) 30° and cranial 25° projections resulting in the highest and lowest exposure levels, respectively. Combined with table-side shielding, the ceiling-suspended lead screen reduced the radiation to the PO by 76.8%, 81.9% and 93.5% when placed close to the patient phantom, at the left side and close to the PO, respectively, and reduced the radiation to the assistant by 70.3%, 76.7% and 90.0%, respectively. When placed close to the PO, a ceiling-suspended lead screen provides substantial radiation protection during CA.