Nomogram based on high-frequency shear wave elastography (SWE) to evaluate chronic changes after kidney transplantation.

OBJECTIVES: To construct a nomogram with high-frequency shear wave elastography (SWE) as a noninvasive method to accurately assess chronic changes in renal allografts. METHODS: A total of 191 renal transplantation patients (127 cases in the training group and 64 cases in the verification group) were included in this study. All patients received conventional ultrasound and high-frequency SWE examination, followed directly by biopsy the next day. The chronic changes were divided into mild, moderate, and severe. Multivariate logistic analyses were used to select significant variables, which were used to develop the nomogram. Nomogram models were assessed by receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). RESULTS: The cutoff value of SWE in mild, moderate, and severe chronic changes was 18.9, 22.5, and 27.6 kPa, respectively. The areas under the curve (AUCs) of SWE in the differential diagnosis of mild and moderate to severe chronic changes and mild to moderate and severe chronic changes were 0.817 and 0.870, respectively. Multivariate analysis showed that time since transplantation, proteinuria, glomerular filtration rate, echogenicity, and SWE were independent diagnostic factors for moderate to severe chronic changes (all p < 0.05); thus, a nomogram was successfully developed. The AUCs of the nomogram in the training and validation groups were 0.905 and 0.938, respectively. The high agreement between the model predictions and the actual observations was confirmed by calibration plot and DCA. CONCLUSIONS: Based on SWE, the nomogram provided an insightful and applicable tool to evaluate chronic changes in renal allografts. KEY POINTS: • In kidney transplantation, compared with acute changes, chronic changes are significantly correlated with cortical stiffness. • SWE shows good performance in identifying mild to moderate and severe chronic changes, with an AUC of 0.870. • Time since transplantation, proteinuria, glomerular filtration rate, echogenicity, and SWE are independent diagnostic factors for moderate to severe chronic changes in renal allografts.

High-Frequency US for BK Polyomavirus-associated Nephropathy after Kidney Transplant.

Background BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of chronic renal allograft dysfunction. However, US features indicative of BKPyVAN have not been fully evaluated. Purpose To assess the value of high-frequency US for the diagnosis of BKPyVAN in kidney transplant recipients. Materials and Methods In this prospective cohort study, participants who tested positive for BK viruria after kidney transplant from September 2019 to January 2021 were evaluated with high-frequency US 1 day before biopsy. Clinical characteristics and US features were compared between participants with and without BKPyVAN. Significant predictors associated with BKPyVAN were determined using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance. Results A total of 105 participants who underwent kidney transplant (mean age, 38 years ± 11 [SD]; 63 men) were evaluated; 45 participants were diagnosed with BKPyVAN. Multivariable analysis demonstrated that eccentric hydronephrosis and subcapsular hypoechoic areas were independent factors for BKPyVAN. The AUC for predicting BKPyVAN according to subcapsular hypoechoic areas was 0.66 (95% CI: 0.55, 0.77), with a specificity of 92% (55 of 60 participants). The AUC of combined US (eccentric hydronephrosis plus subcapsular hypoechoic area) and clinical (urine BKPyV DNA load [BKPyV-DNA] plus BK viremia) features was 0.90, with a specificity of 92% (55 of 60 participants). Parenchymal hyperechoic and subcapsular hypoechoic areas were independent factors for differentiating BKPyVAN from transplant rejection. The pooled specificity of subcapsular hypoechoic areas was 96% (21 of 22 participants), with an AUC of 0.67 (95% CI: 0.54, 0.80). For the combination of US (parenchymal echogenicity plus subcapsular hypoechoic area) and clinical (urine BKPyV-DNA plus time since transplant) features, the AUC reached 0.92 and specificity was 82% (18 of 22 participants). Conclusion High-frequency US characteristics are valuable for diagnosing BK polyomavirus-associated nephropathy (BKPyVAN) and distinguishing BKPyVAN from rejection in kidney transplant recipients. © RSNA, 2022 Online supplemental material is available for this article.

Percutaneous thermal ablation of hepatic tumors: local control efficacy and risk factors for artificial ascites failure.

OBJECTIVE: To investigate the risk factors affecting the technical failure of artificial ascites (AA) formation and to evaluate the local control efficacy of percutaneous thermal ablation assisted by the AA for hepatic tumors. METHODS: A total of 341 patients with 362 hepatic tumors who underwent thermal ablation assisted by AA were reviewed retrospectively. The technical success of AA, the volume of liquid, and local efficacy after ablation were assessed. Predictive factors for the technical failure of AA formation and local tumor progression (LTP) were analyzed using univariate and multivariate analysis. RESULTS: The technical success rate of AA formation was 81.8% (296/362). The amount of fluid was higher when the tumor was located in the left lobe of the liver than when it was located in the right lobe (median 950 ml versus 700 ml, p < 0.001). Previous hepatic resection (OR: 12.63, 95% CI: 2.93-54.45, p < 0.001), ablation (OR: 6.48, 95% CI: 1.36-30.92, p = 0.019) and upper-abdomen surgery (OR: 11.34, 95% CI: 1.96-65.67, p = 0.007) were the independent risk factors of AA failure. In the AA success group, the complete ablation rate was higher and the LTP rate was lower than that in the AA failure group (98.7 versus 92.4%, p = 0.012; 8.8 versus 21.2%, p = 0.004). Multivariate analysis identified AA failure (p = 0.004), tumor size (>3.0 cm) (p = 0.002) and metastatic liver tumor (p = 0.008) as independent risk factors for LTP. CONCLUSION: History of hepatic resection, ablation and upper abdomen surgery were significant predictive factors affecting the technical failure of AA formation. Successful introduction of AA before thermal ablation can achieve better local tumor control efficacy.

Radiofrequency ablation versus hepatic resection for recurrent hepatocellular carcinoma: an updated meta-analysis.

BACKGROUND: The clinical benefits of treatment with radiofrequency ablation (RFA) and repeat hepatic resection (RHR) for recurrent hepatocellular carcinoma (RHCC) remain controversial. This meta-analysis aims to evaluate the outcomes and major complications of RFA versus RHR in patients with early-stage RHCC. METHODS: PubMed, Embase, Web of Science and the Cochrane Library were systematically searched for comparative studies on the evaluation of RHR versus RFA for RHCC. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and major complications. Meta-analysis was performed using a random-effects model or fixed-effects model, and heterogeneity was tested by the Cochran Q statistic. RESULTS: Ten studies with 1612 patients (RHR = 654, RFA = 958) were included in the meta-analysis. The meta-analysis showed that RHR had superior OS (HR 0.77, 95% CI =0.65-0.92, P = 0.004) and PFS (HR 0.81, 95% CI =0.67-0.98, P = 0.027) compared to RFA, whereas major complications may be less frequent in the RFA group (OR 0.15, 95% CI = 0.06-0.39, P < 0.001). In the subgroup analysis of patients with single RHCC ≤3 cm, OS (HR 1.03, 95% CI =0.69-1.52, P = 0.897) and PFS (HR 0.99, 95% CI = 0.71-1.37, P = 0.929) showed no significant differences in the comparison of RHR and RFA. In single RHCC> 3 cm and ≤ 5 cm, RFA showed an increased mortality in terms of OS (HR 0.57, 95% CI = 0.37-0.89, P = 0.014). CONCLUSION: RHR offers a longer OS and PFS than RFA for patients with RHCC, but no statistically significant difference was observed for single RHCC ≤3 cm. The advantages of fewer major complications may render RFA an alternative treatment option for selected patients.

Lesion outline and thermal field distribution of ablative in vitro experiments in myocardia: comparison of radiofrequency and laser ablation.

OBJECTIVES: To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro. MATERIALS AND METHODS: Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously. RESULTS: All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J. CONCLUSIONS: Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.

Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study.

Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.

Stereotactic body radiation therapy versus radiofrequency ablation in hepatocellular carcinoma: an up-date meta-analysis.

PURPOSE: Radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) are available locoregional curative treatments for nonsurgical Hepatocellular carcinoma (HCC) patients. We aimed to compare the clinical efficacy and safety of SBRT versus RFA for HCC. METHODS: A computerized bibliographic search was performed using PubMed, Embase, the Cochrane Library and Web of Science to identify comparative studies. The primary outcome was overall survival (OS), and the secondary outcomes were freedom from local progression (FFLP) and treatment-related complications. RESULTS: In total, there were 17 trials involving 22,180 patients. Patients receiving RFA showed significantly better 1-, 2- year OS (OR 0.69, 95% CI 0.50-0.96, P = 0.141,OR 0.69, 95% CI 0.53-0.89, P = 0.082), whereas SBRT resulted in significantly better 1-, 2-, 3- year FFLP (OR 2.19, 95% CI 1.44-3.34, P = 0.303; OR 1.57, 95% CI 1.12-2.19, P = 0.268; OR 2.22, 95% CI 1.70-2.90, P = 0.470). There were no significant differences for 3-, 5- year OS in both groups (OR 0.94, 95% CI 0.65-1.38, P = 0.001; OR 0.98, 95% CI 0.68-1.34, P = 0.016). The overall treatment-related complication rate did not differ significantly between the two treatment arms, while SBRT was significantly associated with Child-Pugh worsening. CONCLUSIONS: Though SBRT has excellent FFLP, RFA yields superior short-term survival for HCC. But the discrepancy between FFLP and OS requires further investigation.

Ultrasound-Guided Human Islet Transplantation: Safety, Feasibility, and Efficacy Analysis.

RATIONALE AND OBJECTIVES: We aimed to analyze the safety, feasibility, and efficacy of human islet transplantation (IT) using ultrasound (US) throughout the entire procedure. MATERIALS AND METHODS: A total of 22 recipients (18 males; mean age 42.6 ± 17.5years) with 35 procedures were retrospective included. Under US guidance, percutaneous transhepatic portal catheterization was successfully performed through a right-sided transhepatic approach, and islets were infused into the main portal vein. Color Doppler and contrast-enhanced ultrasound were used to guide the procedure and monitor the complications. After infusion of the islet mass, the access track was embolized by embolic material. If hemorrhage persisted, US-guided radiofrequency ablation (RFA) was performed to stop bleeding. Factors that could affect the complication were analyzed. After transplantation, primary graft function was evaluated with a ß-score 1month after the last islet infusion. RESULTS: The technical success rates were 100% with a single puncture attempt. Six (17.1%) abdominal bleeding episodes were immediately stopped by US-guided RFA. No portal vein thrombosis were encountered. Dialysis (OR (Odd Ratio): 32.0; 95% CI: 1.561-656.054; and P = .025) was identified as a significant factor associated with bleeding. Primary graft function was optimal in eight patients (36.4%), suboptimal in 13 patients (59.1%), and poor in one patient (4.5%). CONCLUSION: In conclusion, whole-procedure US-guided IT is a safe, feasible, and effective method for diabetes. Complications are either self-limiting or manageable with noninvasive treatment.

Shear wave elastography using high-frequency linear probe for kidney transplant monitoring: A methodological study.

OBJECTIVES: To investigate the influencing factors of the image quality of shear wave elastography (SWE) performed using a high-frequency probe and its reproducibility for renal allografts. METHODS: A total of 211 patients with transplanted kidneys who underwent SWE examination performed using high-frequency or low-frequency probes were recruited for the study. The reproducibility of inter- and intraobserver agreements were analysed by using the intraclass correlation coefficient (ICC). According to the colour filling of the area of interest and imaging noise when conducting SWE, the image quality was classified as three grades: "good", "common", and "poor". A logistic regression was used to analyse the independent factors for SWE quality. RESULTS: In the comparative analysis, high frequency, transection measurement and middle pole were selected as the appropriate measurement methods. Regarding reproducibility, the ICCs) of the intra- and interobserver agreements were 0.85 and 0.77, respectively. Multivariate analysis indicated that only the skin allograft distance and kidney width were independent variables for SWE quality. In the subgroup analysis of the skin-allograft distance, the "good" and "common" rates of images decreased as the distance increased, but the CV (coefficients of variation) showed the opposite trend. The SWE quality of kidney width <5.4 cm was significantly better than that of kidney width ≥5.4 cm. CONCLUSIONS: High-frequency SWE can be used in the evaluation of transplanted kidneys due to its good repeatability and high successful measurement rate, but we should pay attention to the influence of the skin-allograft distance and kidney width on SWE quality.

Generation of a human induced pluripotent stem cell line (SYSUTFi001-A) from infiltrating cytotoxic T cells in hepatocellular carcinoma (HCC).

In this study, we report a novel induced pluripotent stem cell (iPSC) line SYSUTFi001-A derived from cytotoxic T cells (CTLs) infiltrating in hepatocellular carcinoma (HCC), using an integrative Sendai virus vector. This pluripotent cell line shows a normal karyotype and can be redifferentiated to the rejuvenated CTLs targeted to HCC. The cell line SYSUTFi001-A can be further used to perform vitro and vivo anti-tumor assays and design future cell replacement therapies.

Integrative network analysis of circular RNAs reveals regulatory mechanisms for hepatic specification of human iPSC-derived endoderm.

BACKGROUND: Human-induced pluripotent stem cell (hiPSC)-derived functional hepatic endoderm (HE) is supposed to be an alternative option for replacement therapy for end-stage liver disease. However, the high heterogeneity of HE cell populations is still challenging. Hepatic specification of definitive endoderm (DE) is an essential stage for HE induction in vitro. Recent studies have suggested that circular RNAs (circRNAs) determine the fate of stem cells by acting as competing endogenous RNAs (ceRNAs). To date, the relationships between endogenous circRNAs and hepatic specification remain elusive. METHODS: The identities of DE and HE derived from hiPSCs were determined by qPCR, cell immunofluorescence, and ELISA. Differentially expressed circRNAs (DEcircRNAs) were analysed using the Arraystar Human circRNA Array. qPCR was performed to validate the candidate DEcircRNAs. Intersecting differentially expressed genes (DEGs) of the GSE128060 and GSE66282 data sets and the DEcircRNA-predicted mRNAs were imported into Cytoscape for ceRNA networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were involved in the enrichment analysis. Hepatic markers and Wnt/ß-catenin were detected in hsa_circ_004658-overexpressing cells by western blotting. Dual-luciferase reporter assays were used to evaluate the direct binding among hsa_circ_004658, miRNA-1200 and CDX2. DE cells were transfected with miR-1200 mimics, adenovirus containing CDX2, and Wnt/ß-catenin was detected by western blotting. RESULTS: hiPSC-derived DE and HE were obtained at 4 and 9 days after differentiation, as determined by hepatic markers. During hepatic specification, 626 upregulated and 208 downregulated DEcircRNAs were identified. Nine candidate DEcircRNAs were validated by qPCR. In the ceRNA networks, 111 circRNA-miRNA-mRNA pairs were involved, including 90 pairs associated with hsa_circ_004658. In addition, 53 DEGs were identified among the intersecting mRNAs of the GSE128060 and GSE66282 data sets and the hsa_circ_004658-targeted mRNAs. KEGG and GO analyses showed that the DEGs associated with hsa_circ_004658 were mainly enriched in the WNT signalling pathway. Furthermore, hsa_circ_004658 was preliminarily verified to promote hepatic specification, as determined by hepatic markers (AFP, ALB, HNF4A, and CK19) (p < 0.05). This promotive effect may be related to the inhibition of the Wnt/ß-catenin signalling pathway (detected by ß-catenin, p-ß-catenin, and TCF4) when hsa_circ_004658 was overexpressed (p < 0.05). Dual-luciferase reporter assays showed that there were binding sites for miR-1200 in the hsa_circ_004658 sequence, and confirmed the candidate DEG (CDX2) as a miR-1200 target. The level of miR-1200 decreased and the level of CDX2 protein expression increased when hsa_circ_004658 was overexpressed (p < 0.05). In addition, the results showed that CDX2 may suppress the Wnt/ß-catenin signalling during hepatic specification (p < 0.05). CONCLUSIONS: This study analysed the profiles of circRNAs during hepatic specification. We identified the hsa_circ_004658/miR-1200/CDX2 axis and preliminarily verified its effect on the Wnt/ß-catenin signalling pathway during hepatic specification. These results provide novel insight into the molecular mechanisms involved in hepatic specification and could improve liver development in the future.

Polycystic ovary syndrome is an independent risk factor for hypertensive disorders of pregnancy: A systematic review, meta-analysis, and meta-regression.

PURPOSE: The risk of hypertensive disorders of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS) is inconsistent in some studies. The aim of this meta-analysis was to examine the evidence regarding the strength of the association between PCOS and HDP. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched to identify observational studies investigating HDP in patients with PCOS. The primary outcome was the pooled odds ratio (OR) of HDP, including pregnancy-induced hypertension (PIH) and pre-eclampsia (PE), in women with PCOS compared with the non-PCOS population. RESULTS: A total of 30 studies were eligible for meta-analysis. PCOS was associated with a higher risk of HDP (OR 2.02, 95CI% 1.83-2.22), including PIH (OR 1.94, 95CI% 1.70-2.21), and PE (OR 2.07, 95CI% 1.91-2.24). The association remained significant after adjusting for age, body mass index (BMI), and nulliparity (HDP: OR 1.48, 95CI% 1.48-1.60; PIH: OR 1.42, 95%CI 1.29-1.57; PE: OR 2.07, and 95%CI 1.91-2.24). The increased risk of HDP for the PCOS group remained significant in subgroups of BMI, Age, singleton pregnancy, multiple pregnancy, gestational diabetes mellitus (GDM), hyperandrogenism, and nulliparity, while the finding was not observed in subgroups of nonhyperandrogenic and non-GDM. In the meta-regression, BMI contributed significantly to the heterogeneity in the prevalence of HDP. CONCLUSIONS: PCOS is independently associated with a significantly increased risk of HDP. To prevent HDP during pregnancy, our findings highlight the importance of establishing supervision guidelines for PCOS patients, especially in the population with hyperandrogenism and GDM.

Differential diagnosis of liver metastases of gastrointestinal stromal tumors from colorectal cancer based on combined tumor biomarker with features of conventional ultrasound and contrast-enhanced ultrasound.

PURPOSE: To explore the value of tumor marker CA125 and CEA linked with conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) features in differentiating gastrointestinal stromal tumors liver metastases (GISTLM) from colorectal cancer liver metastases (CRCLM). MATERIALS AND METHODS: From December 2005 to February 2019, eighty patients with pathologically proven GISTLM together with 80 CRCLM patients were retrospectively evaluated with contrast-enhanced ultrasound (CEUS). Clinical characteristics such as CA125 and CEA were documented to compare the difference between GISTLM and CRCLM. Univariate analysis was performed to determine significant features in ultrasound and then these features were entered into multivariate logistic regression model to determine diagnostic criteria. By analyzing the tumor marker and imaging features, diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. The sensitivity, specificity and accuracy were calculated for the diagnosis of GISTLM. RESULTS: Multiple logistic regression analysis showed that increased CA125 and normal CEA were the independent variables of GISTLM. On conventional US, the features of hypo- or mix-echogenicity and anechoic area were associated with GISTLM. On CEUS, capsule enhancement, starting time of washout > 40 s and proportion of non-enhancement area > 20% were the features indicating GISTLM. All of the p values were < 0.05. When linking tumor marker with imaging features, the diagnostic sensitivity improved from 36.3-57.5% to 70.0%, and the area under the ROC (AUROC) curve improved from 0.681-0.750 to 0.838, with a specificity of 97.5%. CONCLUSIONS: Combining the imaging features of conventional US and CEUS with serum tumor markers provides a potentially effective diagnostic method in differentiation of GISTLM and CRCLM.