Medullary sponge kidney with IgA nephropathy: a case report and literature review.

BACKGROUND: Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy. CASE PRESENTATION: A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient's clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy. CONCLUSIONS: Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.

Automatic detection of thyroid nodules with a real-time artificial intelligence system in a real clinical scenario and the associated influencing factors.

BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (P = 0.013), but lower than that of senior radiologist (P = 0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all P < 0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (P < 0.001) and 99.1% (P = 0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.

TDO2 promotes bladder cancer progression via AhR-mediated SPARC/FILIP1L signaling.

The enzyme tryptophan 2,3-dioxygenase (TDO2) has been implicated in the dysregulation across a variety of human cancers. Despite this association, the implications of TDO2 in the progression of bladder cancer have eluded thorough understanding. In this study, we demonstrate that TDO2 expression is notably elevated in bladder cancer tissues and serves as an unfavorable prognostic factor for overall survival. Through a series of biological functional assays, we have determined that TDO2 essentially enhances cell proliferation, metastatic potential, and imparts a decreased sensitivity to the chemotherapeutic agent cisplatin. Our mechanistic investigations reveal that TDO2 augments aryl hydrocarbon receptor (AhR) signaling pathways and subsequently upregulates the expression of SPARC and FILIP1L. Importantly, we have identified a positive correlation between TDO2 levels and the basal/squamous subtype of bladder cancer, and we provide evidence to suggest that TDO2 expression is modulated by the tumor suppressors RB1 and TP53. From a therapeutic perspective, we demonstrate that the targeted inhibition of TDO2 with the molecular inhibitor 680C91 markedly attenuates tumor growth and metastasis while concurrently enhancing the efficacy of cisplatin. These findings open a new therapeutic avenue for the management of bladder cancer.

Risk stratification model for incidentally detected gallbladder polyps: A multicentre study.

PURPOSE: We aimed to develop a 4-level risk stratification model using a scoring system based on conventional ultrasound to improve the diagnosis of gallbladder polyp. METHOD: Patients with histopathologically confirmed gallbladder polyps were consecutively recruited from three medical centres. Conventional ultrasound findings and clinical characteristics were acquired prior to cholecystectomy. Risk factors for neoplastic and malignant polyps were used to build a risk stratification system via interobserver agreement and multivariate logistic regression analysis. The model was retrospectively trained using 264 pre-surgical samples and prospectively validated using 106 pre-surgical samples. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and malignant polyp rate. RESULTS: In total, 370 patients (mean age, 51.68 ± 14.41 years, 156 men) were enrolled in this study. Size (≥12 mm), shape (oblate or round), single, vascularity, gallbladder stone or sludge were considered risk factors for neoplastic polyps. Size (≥14 mm), shape (oblate), single, disrupted gallbladder wall, and gallbladder stone or sludge were risk factors for malignant polyps (all p < 0.05). In the scoring system, the sensitivity, specificity, and AUC of score ≥ 9 in diagnosing neoplastic polyps were 0.766, 0.788, and 0.876 respectively; and the sensitivity, specificity, and AUC of score ≥ 15 in diagnosing malignant polyps were 0.844, 0.926, and 0.949 respectively. In our model, the malignancy rates at the four levels were 0 % (0/24), 1.28 % (2/156), 9.26 % (5/54), and 70.37 % (38/54), respectively. CONCLUSIONS: The 4-level risk stratification model based on conventional ultrasound imaging showed excellent performance in classifying gallbladder polyps.

Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis.

PURPOSE: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. METHODS: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. RESULTS: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. CONCLUSION: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging.

Objective: Endomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model. Methods: Microbubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting. Results: After MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups. Conclusion: Ultrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation.

3D-CEUS tracking of injectable chemo-sonodynamic therapy-enabled mop-up of residual renal cell carcinoma after thermal ablation.

Thermal ablation (TA), as a minimally invasive therapeutic technique, has been extensively used to the treatment of solid tumors, such as renal cell carcinoma (RCC), which, unfortunately, still fails to overcome the high risk of local recurrence and distant metastasis since the incomplete ablation cannot be ignored due to various factors such as the indistinguishable tumor margins and limited ablation zone. Herein, we report the injectable thermosensitive hydrogel by confining curcumin (Cur)-loaded hollow mesoporous organosilica nanoparticles (Cur@HMON@gel) which can locate in tumor site more than half a month and mop up the residual RCC under ultrasound (US) irradiation after transforming from colloidal sol status to elastic gel matrix at physiological temperature. Based on the US-triggered accelerated diffusion of the model chemotherapy drug with multi-pharmacologic functions, the sustained and controlled release of Cur has been demonstrated in vitro. Significantly, US is employed as an external energy to trigger Cur, as a sonosensitizer also, to generate reactive oxygen species (ROS) for sonodynamic tumor therapy (SDT) in parallel. Tracking by the three-dimensional contrast-enhanced ultrasound (3D-CEUS) imaging, the typical decreased blood perfusions have been observed since the residual xenograft tumor after incomplete TA were effectively suppressed during the chemo-sonodynamic therapy process. The high in vivo biocompatibility and biodegradability of the multifunctional nanoplatform confined by thermogel provide the potential of their further clinical translation for the solid tumor eradication under the guidance and monitoring of 3D-CEUS.

Efficacy of contrast-enhanced ultrasound-guided percutaneous core needle biopsy in anterior mediastinal masses.

Objective: To evaluate the efficacy and safety of percutaneous core needle biopsy (PCNB) using ultrasound (US)-guided and contrast-enhanced ultrasound (CEUS)-guided procedures for anterior mediastinal masses (AMMs). Methods: In total, 284 consecutive patients (166 men, 118 women; mean age, 43.0 â€‹± â€‹18.4 years) who underwent PCNB for AMMs were enrolled. Patients were divided into the US-guided group (n â€‹= â€‹133) and the CEUS-guided group (n â€‹= â€‹151). PCNB was performed using a core needle (16-gauge or 18-gauge). Internal necrosis, diagnostic yield, and diagnostic accuracy were compared between the two groups. Results: The predominant final diagnosis of the cases in this study was thymoma (29.7%), lymphoma (20.5%), thymic carcinoma (13.3%), and germ cell tumour (13.3%), respectively. There was no significant difference in patient age, sex, number of percutaneous biopsies, or display rate of internal necrosis on conventional US between the two groups. The rate of internal necrosis of the lesions was significantly higher after contrast agent injection (72.2% vs. 41.7%; P â€‹< â€‹0.001). The CEUS-guided group had a higher diagnostic yield than the US-guided group (100% vs. 89.5%, P â€‹< â€‹0.001). There was no significant difference between the diagnostic accuracy of the CEUS-guided and US-guided groups (97.3% vs. 97.4%; P â€‹= â€‹1.000). None of the patients experienced adverse reactions or complications after US-guided or CEUS-guided PCNB. Conclusions: CEUS-guided PCNB can improve the diagnostic yield by optimizing the biopsy procedure.

TET2 Suppresses VHL Deficiency-Driven Clear Cell Renal Cell Carcinoma by Inhibiting HIF Signaling.

Inactivating mutations of von Hippel-Lindau (VHL) are highly prevalent in clear cell renal cell carcinoma (ccRCC). Improved understanding of the vulnerabilities of VHL-deficient ccRCC could lead to improved treatment strategies. The activity of DNA dioxygenase ten-eleven translocation (TET)2 is significantly reduced in multiple cancers by different mechanisms, but its role in ccRCC progression remains unclear. Here, we report that increased expression of TET2, but not TET1 and TET3, is negatively associated with tumor metastasis and advanced tumor stage and is positively associated with good prognosis uniquely in ccRCC among all 33 types of cancer in The Cancer Genome Atlas datasets. TET2 restrained glycolysis and pentose phosphate pathway metabolism in a VHL deficiency-dependent manner, thereby suppressing ccRCC progression. Notably, TET2 and VHL mutations tended to cooccur in ccRCC, providing genetic evidence that they cooperate to inhibit the progression of ccRCC. Mechanistically, TET2 was recruited by transcription factor HNF4α to activate FBP1 expression, which antagonized the function of hypoxia-inducible factor-1/2α (HIF1/2α) in metabolic reprogramming to impede ccRCC growth. Stimulating the TET2-FBP1 axis with vitamin C repressed the growth of VHL-deficient ccRCC with wild-type TET2 and increased the sensitivity to glycolysis inhibitors. Moreover, combined expression levels of the HNF4α-TET2-FBP1 axis served as a biomarker of prognosis in patients with ccRCC. This study reveals a unique function of TET2 in the suppression of tumor metabolism and HIF signaling, and it also provides therapeutic targets, potential drugs, and prognostic markers for the management of ccRCC. SIGNIFICANCE: The identification of TET2-mediated inhibition of HIF signaling and tumor metabolic reprogramming provides insights for new therapeutic strategies for VHL-deficient ccRCC.

Evaluation of Plasma Extracellular Vesicle MicroRNA Signatures for Lung Adenocarcinoma and Granuloma With Monte-Carlo Feature Selection Method.

Extracellular Vesicle (EV) is a compilation of secreted vesicles, including micro vesicles, large oncosomes, and exosomes. It can be used in non-invasive diagnosis. MicroRNAs (miRNAs) processed by exosomes can be detected by liquid biopsy. To objectively evaluate the discriminative ability of miRNAs from whole plasma, EV and EV-free plasma, we analyzed the miRNA expression profiles in whole plasma, EV and EV-free plasma of 10 lung adenocarcinoma and 9 granuloma patients. With Monte-Carlo feature selection method, the top discriminative miRNAs in whole plasma, EV and EV-free plasma were identified, and they were quite different. Using the Repeated Incremental Pruning to Produce Error Reduction (RIPPER) method, we learned the classification rules: in whole plasma, granuloma patients did not express hsa-miR-223-3p while the lung adenocarcinoma patients expressed hsa-miR-223-3p; in EV, the hsa-miR-23b-3p was highly expressed in granuloma patients but not lung adenocarcinoma patients; in EV-free plasma, hsa-miR-376a-3p was expressed in granuloma patients but barely expressed in lung adenocarcinoma patients. For prediction performance, whole plasma had the highest weighted accuracy and EV outperformed EV-free plasma. Our results suggested that EV can be used as lung cancer biomarker. However, since it is less stable and not easy to detect, there are still technological difficulties to overcome.

Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse.

Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation.

Primary non-Hodgkin's lymphoma of the liver: sonographic and CT findings.

BACKGROUND: A preoperative diagnosis of primary hepatic lymphoma (PHL) can have profound therapeutic and prognostic implications. Because of the rarity of PHL, however, there are few reports on diagnostic imaging. We reviewed the clinical and radiologic findings of 29 patients with PHL, the largest series to date, to evaluate the diagnostic features of this disease. METHODS: Clinical data and radiologic findings at presentation were retrospectively reviewed for 29 patients with pathologically confirmed PHL from January 2005 to June 2013. Imaging studies, including ultrasound (US) (n=29) and contrast-enhanced computed tomography (CECT) (n=24), were performed within 2 weeks before biopsy or surgery. RESULTS: Among the 29 patients, 23 (79%) were positive for hepatitis B virus (HBV) and 26 (90%) had a significantly elevated level of serum lactate dehydrogenase (LDH). There were two distinct types of PHL on imaging: diffuse (n=5) and nodular (n=24). Homogeneous or heterogeneous hepatomegaly was the only sign for diffuse PHL on both US and CECT, without any definite hepatic mass. For the nodular type, 63% (15/24) of patients had solitary lesions and 38% (9/24) had multiple lesions. On US, seven patients displayed patchy distribution with an indistinct tumor margin and a rich color flow signal. CECT showed rim-like enhancement (n=3) and slightly homogeneous or heterogeneous enhancement (n=14) in the arterial phase and isoenhancement (n=5) and hypoenhancement (n=12) in the portal venous and late phases. Furthermore, in five patients, CT revealed that hepatic vessels passed through the lesions and were not displaced from the abnormal area or appreciably compressed. CONCLUSIONS: The infiltration type of PHL was associated with the histologic subtype. Considered together with HBV positivity and elevated LDH, homogeneous or heterogeneous hepatomegaly may indicate diffuse PHL, whereas patchy distribution with a rich color flow signal on US or normal vessels extending through the lesion on CECT may be the diagnostic indicators of nodular PHL.

A novel simple noninvasive index to predict renal transplant acute rejection by contrast-enhanced ultrasonography.

PURPOSE: This study aimed to evaluate the application of quantitative contrast-enhanced ultrasonography (CEUS) in the assessment of renal allograft dysfunction and to establish a new noninvasive index to predict acute rejection (AR). METHODS: Fifty-seven renal transplant recipients were enrolled in this prospective study. Before renal allograft biopsy, CEUS examinations were performed.The biopsy results proved 23 cases of AR (AR group), 10 cases of acute tubular necrosis (ATN group), and 24 with normal evolution (stable group). Contrast-enhanced ultrasonography parameters including rising time (RT), time to peak (TTP), and the delta-time among regions of interest (ΔRT and ΔTTP) were analyzed. RESULTS: In the AR group, RT and TTP of interlobar artery and medulla (RTi, RTm, TTPi, and TTPm) as well as ΔRT and ΔTTP between medulla and cortex (ΔRTm-c and ΔTTPm-c) were significantly higher compared with those in the stable group. RTm and TTPm as well as ΔRTm-c and ΔTTPm-c were remarkably higher compared with those in the ATN group. ΔRTm-c and estimated glomerular filtration rate (eGFR) were identified as independent predictors by multivariate analysis (P = 0.008 and P = 0.024). On the basis of the multivariate analysis results and area under the receiver operating characteristic curves of individual markers, we constructed a new simple index, P = -0.587 + 0.286 ×ΔRTm-c − 0.028 × eGFR; new index = e(P)/(1 + e(P)), to discriminate AR, which had better area under the receiver operating characteristic curves than eGFR or individual CEUS parameters. CONCLUSION: Contrast-enhanced ultrasonography parameters are reliable markers for differentiating the perfusion status of transplanted kidneys. Furthermore, the new simple index can easily predictAR with a high degree of accuracy.

Tissue elasticity quantification by acoustic radiation force impulse for the assessment of renal allograft function.

Acoustic radiation force impulse (ARFI) quantification, a novel ultrasound-based elastography method, has been used to measure liver fibrosis. However, few studies have been performed on the use of ARFI quantification in kidney examinations. We evaluated renal allograft stiffness using ARFI quantification in patients with stable renal function (n = 52) and those with biopsy-proven allograft dysfunction (n = 50). ARFI quantification, given as shear wave velocity (SWV), was performed. The resistance index (RI) was calculated by pulsed-wave Doppler ultrasound, and clinical and laboratory data were collected. Morphologic changes in transplanted kidneys were diagnosed by an independent pathologist. Mean SWV was more significantly negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.657, p < 0.0001) than was RI (r = -0.429, p = 0.0004) in transplanted kidneys. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of quantitative ultrasound in the diagnosis of renal allograft dysfunction were 72.0% and 86.5% (cutoff value = 2.625), respectively. The latter values were better than those of RI, which were 62.0% and 69.2% (cutoff value = 0.625), respectively. The coefficient of variation for repeat SWV measurements of the middle part of transplanted kidney was 8.64%, and inter-observer agreement on SWV was good (Bland-Altman method, ICC = 0.890). In conclusion, tissue elasticity quantification by ARFI is more accurate than the RI in diagnosing renal allograft function.

[Intravenous contrast-enhanced ultrasound of metastatic lymph nodes in rabbit VX2 tongue carcinoma model].

OBJECTIVE: To investigate the sonographic features of the cervical lymph nodes in rabbit VX2 tongue carcinoma model and hyperplasia cervical lymph nodes model using gray scale contrast-enhanced ultrasonography (CEUS) after intravenous administration of SonoVue (a sonographic contrast agent) and to evaluate the potential utility of CEUS in detecting early metastatic cervical lymph nodes in the rabbit VX2 tongue carcinoma model. METHODS: Twenty New Zealand rabbits were placed into 2 groups, 12 for node metastasis and 18 for node hyperplasia. Cervical CEUS was performed in the rabbits of both groups before and after intravenous administration of SonoVue(0.6 ml). The phase, pattern, beginning area and echogenicity of enhancement of the lymph nodes on the right neck were observed and recorded. Dissection of the lymph nodes were guided by the marks made during CEUS and examined histopathologically. RESULTS: On the right side of each rabbit only one lymph node were detected in both groups. All 8 cases in the hyperplasia group showed homogeneous enhancement starting from central, while in the metastasis group one case showed homogeneous enhancement starting from the central, 3 cases showed inhomogeneous enhancement starting from periphery, and 8 cases showed inhomogeneous enhancement starting both from central and periphery. One lymph node was dissected on the right side of the neck in each rabbit in both groups. Pathological examination showed all 12 lymph nodes in the metastatic group were metastatic lymph nodes, and all 8 lymph nodes in the hyperplasia group were hyperplastic lymph nodes. CONCLUSIONS: After intravenous CEUS, metastatic lymph nodes show inhomogeneous enhancement starting from periphery/central or periphery area, while hyperplastic lymph nodes show homogeneous enhancement starting from central area. Metastatic lymph nodes can be characterized as being neoplastic or benign on the basis of the enhancement patterns evaluated by CEUS.