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1.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807864

ABSTRACT

INTRODUCTION: Chronic inflammation and impaired neovascularization play critical roles in delayed wound healing in diabetic patients. To overcome the limitations of current diabetic wound (DBW) management interventions, we investigated the effects of a catechol-functionalized hyaluronic acid (HA-CA) patch combined with adipose-derived mesenchymal stem cells (ADSCs) in DBW mouse models. METHODS: Diabetes in mice (C57BL/6, male) was induced by streptozotocin (50 mg/kg, >250 mg/dL). Mice were divided into four groups: control (DBW) group, ADSCs group, HA-CA group, and HA-CA + ADSCs group (n = 10 per group). Fluorescently labeled ADSCs (5 × 105 cells/100 µL) were transplanted into healthy tissues at the wound boundary or deposited at the HA-CA patch at the wound site. The wound area was visually examined. Collagen content, granulation tissue thickness and vascularity, cell apoptosis, and re-epithelialization were assessed. Angiogenesis was evaluated by immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot. RESULTS: DBW size was significantly smaller in the HA-CA + ADSCs group (8% ± 2%) compared with the control (16% ± 5%, p < 0.01) and ADSCs (24% ± 17%, p < 0.05) groups. In mice treated with HA-CA + ADSCs, the epidermis was regenerated, and skin thickness was restored. CD31 and von Willebrand factor-positive vessels were detected in mice treated with HA-CA + ADSCs. The mRNA and protein levels of VEGF, IGF-1, FGF-2, ANG-1, PIK, and AKT in the HA-CA + ADSCs group were the highest among all groups, although the Spred1 and ERK expression levels remained unchanged. CONCLUSIONS: The combination of HA-CA and ADSCs provided synergistic wound healing effects by maximizing paracrine signaling and angiogenesis via the PI3K/AKT pathway. Therefore, ADSC-loaded HA-CA might represent a novel strategy for the treatment of DBW.


Subject(s)
Adipose Tissue/metabolism , Bandages , Diabetes Mellitus, Experimental/therapy , Diabetic Angiopathies/therapy , Hyaluronic Acid , Stem Cell Transplantation , Stem Cells/metabolism , Wound Healing , Wounds and Injuries/therapy , Adipose Tissue/pathology , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Angiopathies/metabolism , Diabetic Angiopathies/pathology , Female , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Male , Mice , Stem Cells/pathology , Wounds and Injuries/metabolism , Wounds and Injuries/pathology
2.
Eur Radiol ; 2021 Apr 21.
Article in English | MEDLINE | ID: mdl-33884471

ABSTRACT

OBJECTIVES: To compare the image quality and diagnostic performance of 2D MRCP to those of breath-hold 3D MRCP using compressed sensing (CS-MRCP) and gradient and spin-echo (GRASE-MRCP) at 3T. METHODS: From January to November 2018, patients who underwent pancreatobiliary MRI including 2D MRCP and two breath-hold 3D MRCP using CS and GRASE at 3T were included. Three radiologists independently evaluated image quality, motion artifact, and pancreatic cyst conspicuity. Diagnostic performance was assessed for bile duct anatomic variation, bile duct, and pancreatic diseases using a composite algorithm as reference standards. Pancreatic lesion detectability and conspicuity were evaluated using JAFROC and generalized estimating equation analysis. RESULTS: One hundred patients (male = 50) were included. Bile duct anatomic variation, bile duct and pancreatic diseases were present in respectively 31, 15, and 79 patients. Breath-hold 3D MRCP provided better image quality than 2D MRCP (3.5 ± 0.6 in 2D MRCP; 4.0 ± 0.7 in GRASE-MRCP and 3.9 ± 0.8 in CS-MRCP, p < 0.001 for both). There was no difference in motion artifact between 2D and breath-hold 3D MRCP (p = 0.1). Breath-hold 3D CS-MRCP provided better pancreatic cyst conspicuity than 2D MRCP (2.7 [95% CI: 2.5-3.0] vs. 2.3 [95% CI: 2.1-2.5], p = 0.001). There were no significant differences between the diagnostic performance of the three sequences in the detection of bile duct anatomic variation or pancreatic lesions (p > 0.05). CONCLUSION: Breath-hold 3D MRCP with GRASE or CS can provide better image quality than 2D MRCP in a comparable scan time. KEY POINTS: • Breath-hold 3D MRCP using compressed sensing (CS) or gradient and spin-echo (GRASE) provided a better image quality with less image blurring than 2D MRCP. • There were no significant differences between 2D MRCP and breath-hold 3D MRCP in either motion artifact or the number of non-diagnostic exams. • There were no significant differences between 2D MRCP and either type of breath-hold 3D MRCP in the diagnosis of bile duct anatomic variation or detection of pancreatic lesions.

3.
Eur Radiol ; 2021 Apr 21.
Article in English | MEDLINE | ID: mdl-33881566

ABSTRACT

OBJECTIVES: To develop a convolutional neural network system to jointly segment and classify a hepatic lesion selected by user clicks in ultrasound images. METHODS: In total, 4309 anonymized ultrasound images of 3873 patients with hepatic cyst (n = 1214), hemangioma (n = 1220), metastasis (n = 1001), or hepatocellular carcinoma (HCC) (n = 874) were collected and annotated. The images were divided into 3909 training and 400 test images. Our network is composed of one shared encoder and two inference branches used for segmentation and classification and takes the concatenation of an input image and two Euclidean distance maps of foreground and background clicks provided by a user as input. The performance of hepatic lesion segmentation was evaluated based on the Jaccard index (JI), and the performance of classification was based on accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC). RESULTS: We achieved performance improvements by jointly conducting segmentation and classification. In the segmentation only system, the mean JI was 68.5%. In the classification only system, the accuracy of classifying four types of hepatic lesions was 79.8%. The mean JI and classification accuracy were 68.5% and 82.2%, respectively, for the proposed joint system. The optimal sensitivity and specificity and the AUROC of classifying benign and malignant hepatic lesions of the joint system were 95.0%, 86.0%, and 0.970, respectively. The respective sensitivity, specificity, and the AUROC for classifying four hepatic lesions of the joint system were 86.7%, 89.7%, and 0.947. CONCLUSIONS: The proposed joint system exhibited fair performance compared to segmentation only and classification only systems. KEY POINTS: • The joint segmentation and classification system using deep learning accurately segmented and classified hepatic lesions selected by user clicks in US examination. • The joint segmentation and classification system for hepatic lesions in US images exhibited higher performance than segmentation only and classification only systems. • The joint segmentation and classification system could assist radiologists with minimal experience in US imaging by characterizing hepatic lesions.

4.
AJR Am J Roentgenol ; : 1-9, 2021 Apr 07.
Article in English | MEDLINE | ID: mdl-33826357

ABSTRACT

OBJECTIVE. The purpose of this study is to investigate the detection rate of transabdominal ultrasound (TAUS) for pancreatic cysts incidentally detected on CT or MRI as well as the factors that influence detection rates. SUBJECTS AND METHODS. Fifty-seven patients with low-risk pancreatic cysts (n = 77; cyst size, 5 mm to 3 cm) that were incidentally detected on CT or MRI were prospectively enrolled at five institutions. At each institution, TAUS was independently performed by two radiologists who assessed detection of cysts, cyst location and size, and the diameter of the main pancreatic duct (MPD). Cyst detection rates based on cyst size, location, and multiplicity and the body mass index of the patient were compared using the Mann-Whitney test. Kappa statistics and the interclass correlation coefficient were used to evaluate interobserver agreement regarding cyst detection and consistency of cyst size and the diameter of the MPD on TAUS versus prior CT or MRI. RESULTS. The detection rate for known low-risk pancreatic cysts was 81.8% (63/77) and 83.1% (64/77) for TAUS conducted by each of the two radiologists. The detection rate for larger (≥ 10 mm) cysts was significantly higher than that for smaller cysts (89.0% vs 63.6% for TAUS performed and interpreted by radiologist 1 [TAUS 1] and 89.0% vs 68.2% for TAUS conducted and interpreted by radiologist 2 [TAUS 2]; p < .05). A higher detection rate was noted for cysts located outside the tail of the pancreas compared with those located in the tail (89.5% vs 65.0% for TAUS 2; p = .01), and the detection rate was also significantly higher for single cysts than for multiple cysts (90.9% vs 69.7% for TAUS 1; p = .02). However, no significant difference was observed for body mass index. Interobserver agreement was excellent regarding the size of the detected cysts (inter-class correlation coefficient: 0.964 [95% CI, 0.940-0.979] for CT, TAUS 1, and TAUS 2 and 0.965 [95% CI. 0.924-986] for MRI, TAUS 1, and TAUS 2) and the diameter of the MPD (interclass correlation coefficient, 0.934; 95% CI, 0.898-0.959). CONCLUSION. TAUS could be a useful alternative imaging tool for surveillance of known low-risk pancreatic cysts, especially single pancreatic cysts and those that are of larger size (≥ 1 cm) or are located outside the tail.

5.
Abdom Radiol (NY) ; 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33929600

ABSTRACT

PURPOSE: To predict poor overall survival (OS) and risk of residual tumor after surgery using MR imaging, clinical, and histopathological findings in perihilar cholangiocarcinoma. METHODS: 196 patients with perihilar cholangiocarcinoma who underwent preoperative MRI and curative-intent surgery were retrospectively included. MRI findings were assessed by two radiologists. Clinical characteristics and histopathological results such as serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), T and N stage, and resection status, were also investigated. Cox regression analysis and the Kaplan-Meier method were used to identify prognostic factors for OS. We further analyzed the correlation between MRI features and residual tumors using logistic regression analysis. RESULTS: The median OS was 25.0 ± 26.6 months. T stage (hazard ratio [HR] 6.26, p = 0.014), N stage (HR 1.86, p = 0.002), CA-19-9 >37 U/mL (HR 2.06, p < 0.001), enlarged LN on MRI (HR 1.69, p = 0.006), and residual tumor (HR 1.52, p = 0.034) were important predictors of poor survival. The 5-year OS of the complete resection group (n = 107) was significantly better than that of the residual tumor group (n = 89) (35.5% vs. 18.8%, p = 0.002). Additionally, peritumoral fat stranding (odds ratio[OR] 2.09, p = 0.027), Bismuth type III/IV (OR 1.95, p = 0.022), and common bile duct (CBD) involvement (OR 2.3, p = 0.008) on MRI were important predictors of residual tumors in univariate analyses. However, absence of peritumoral fat stranding was a significant independent predictor for complete resection (OR 1.99, p = 0.048) and showed the highest sensitivity, at 79.8%. CONCLUSION: MR imaging, clinical and histopathological results are useful for predicting poor survival after surgery for perihilar cholangiocarcinoma. Furthermore, MRI findings, including peritumoral fat stranding, CBD involvement, and Bismuth type, are important for the prediction of residual tumors.

6.
Eur J Radiol ; 139: 109687, 2021 Mar 27.
Article in English | MEDLINE | ID: mdl-33836335

ABSTRACT

PURPOSE: This study aimed to investigate the correlation of attenuation between virtual noncontrast (VNC) and true noncontrast (TNC) CT images and compare the diagnostic performance for hepatic steatosis using MR spectroscopy (MRS) as the reference standard. METHODS: A total of 131 consecutive hepatic donor candidates who underwent dual-source dual-energy CT and MRS within one month from January 2018 to April 2019 were included. An MRS value > 5.8 % was regarded as substantial hepatic steatosis. The correlation of attenuation between TNC and VNC in the liver and spleen, and liver attenuation index (LAI), defined as hepatic minus splenic attenuation, was evaluated using Spearman's rank correlation. The diagnostic performance of the LAI for hepatic steatosis was compared using receiver operating characteristic analyses. RESULTS: Twenty-three candidates (17.6 %) had substantial hepatic steatosis. The median liver attenuation (66.7 [IQR, 63.5-70.9] vs. 63.5 [IQR, 60.3-66.9], p < .001) and LAI (12.9 [9.3-16.7] vs. 7.4 [3.9-11.9], p < .001) in the VNC were higher than those in the TNC. Hepatic attenuation (r = 0.93, p < .001), splenic attenuation (r = 0.55, p < .001), and LAI (r = 0.87, p < .001) were significantly correlated between TNC and VNC. Area under the curve of LAI in TNC and VNC were 0.88 (cutoff, LAI < 3.1) and 0.84 (cutoff, LAI < 10.1), respectively, indicating no statistically significant difference (p = 0.11). CONCLUSION: The LAI of VNC is significantly correlated with that of TNC and might be feasible for diagnosing substantial hepatic steatosis in living liver donor candidates using different cutoff values of LAI.

7.
Acta Radiol ; : 284185121999998, 2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33682455

ABSTRACT

BACKGROUND: Complete resection is the only potentially curative treatment in patients with pancreatic ductal adenocarcinoma (PDA) and is associated with a longer overall survival (OS) than incomplete resection of tumor. Hence, prediction of the resection status after surgery would help predict the prognosis of patients with PDA. PURPOSE: To predict residual tumor (R) classification and OS in patients who underwent first-line surgery for PDA using preoperative magnetic resonance imaging (MRI). MATERIAL AND METHODS: In this study, 210 patients with PDA who underwent MRI and first-line surgery were randomly categorized into a test group (n=150) and a validation group (n=60). The R classification was divided into R0 (no residual tumor) and R1/R2 (microscopic/macroscopic residual tumor). Preoperative MRI findings associated with R classification and OS were assessed by using logistic regression and Cox proportional hazard models. In addition, the prediction models for the R classification and OS were validated using calibration plots and C statistics. RESULTS: On preoperative MRI, portal vein encasement (odds ratio 4.755) was an independent predictor for R1/R2 resection (P=0.040). Tumor size measured on MRI (hazard ratio [HR] per centimeter 1.539) was a predictor of OS, along with pathologic N1 and N2 stage (HR 1.944 and 3.243, respectively), R1/R2 resection (HR 3.273), and adjuvant chemoradiation therapy (HR 0.250) (P<0.050). Calibration plots demonstrated satisfactory predictive performance. CONCLUSION: Preoperative MRI was valuable for predicting R1/R2 resection using portal vein encasement. Tumor size measured on MRI was useful for the prediction of OS after first-line surgery for PDA.

8.
Korean J Radiol ; 2021 Mar 09.
Article in English | MEDLINE | ID: mdl-33739633

ABSTRACT

OBJECTIVE: To evaluate the performance of the 2018 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) Practice Guidelines (hereafter, PG) for the diagnosis of hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced MRI, compared to the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 (hereafter, v2018). MATERIALS AND METHODS: From January 2013 to October 2015, treatment-naïve hepatic lesions (≥ 1 cm) on gadoxetic acid-enhanced MRI in consecutive patients with chronic hepatitis B or cirrhosis were retrospectively evaluated. For each lesion, three radiologists independently analyzed the imaging features and classified the lesions into categories according to the 2018 KLCA-NCC PG and LI-RADS v2018. The imaging features and categories were determined by consensus. Generalized estimating equation (GEE) models were used to compare the per-lesion diagnostic performance of the 2018 KLCA-NCC PG and LI-RADS v2018 using the consensus data. RESULTS: In total, 422 lesions (234 HCCs, 45 non-HCC malignancies, and 143 benign lesions) from 387 patients (79% male; mean age, 59 years) were included. In all lesions, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity and lower specificity than LR-5 (LI-RADS v2018) (87.2% [204/234] vs. 80.8% [189/234], p < 0.001; 86.2% [162/188] vs. 91.0% [171/188], p = 0.002). However, in lesions of size ≥ 2 cm, the definite HCC had a higher sensitivity than the LR-5 (86.8% [164/189] vs. 82.0 (155/189), p = 0.002) without a reduction in the specificity (80.0% [48/60] vs. 83.3% [50/60], p = 0.15). In all lesions, the sensitivity and specificity of the definite/probable HCC (2018 KLCA-NCC PG) and LR-5/4 did not differ significantly (89.7% [210/234] vs. 91.5% [214/234], p = 0.204; 83.5% [157/188] vs. 79.3% [149/188], p = 0.071). CONCLUSION: For the diagnosis of HCC of size ≥ 2 cm, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity than LR-5, without a reduction in specificity. The definite/probable HCC (2018 KLCA-NCC PG) had a similar sensitivity and specificity to that those of the LR-5/4.

9.
Radiology ; 299(2): 336-345, 2021 May.
Article in English | MEDLINE | ID: mdl-33650901

ABSTRACT

Background The Liver Imaging Reporting and Data System (LI-RADS), version 2018, treatment response algorithm (TRA) is used to assess hepatocellular carcinoma (HCC) after local-regional therapy (LRT). However, its diagnostic performance has not yet been fully compared between CT and hepatobiliary agent (HBA)-enhanced MRI in patients who have undergone liver transplant (LT). Purpose To compare the diagnostic performance of LI-RADS TRA when using CT versus using HBA-enhanced MRI in an intraindividual manner according to pathologic results. Materials and Methods Between January 2011 and September 2019, 165 patients with 237 clinically suspected HCCs underwent LRT followed by LT and were retrospectively included. All patients underwent both CT and HBA-enhanced MRI after LRT and before LT. Three radiologists independently assessed tumor viability with both modalities by using LI-RADS TRA and reached a consensus. Pathologic tumor viability categorized as either completely (100%) or incompletely (<100%) necrotic obtained from the explanted liver served as the reference standard. Sensitivity and specificity of the LI-RADS TRA in the consensus reading were then compared between CT and HBA-enhanced MRI by using the ratio estimator approach. Interobserver agreements were calculated by using Fleiss κ statistics. Results There were 165 patients (mean age, 62 years ± 9 [standard deviation]; 135 men) with a total of 237 lesions, of which 107 were viable tumors (45.1%) at pathologic evaluation. With the LI-RADS TRA, sensitivity and specificity of the viable category for detection of viable HCCs at pathologic evaluation were 42.1% (45 of 107 lesions) and 95.4% (124 of 130 lesions) with CT and 52.3% (56 of 107 lesions) and 93.9% (122 of 130 lesions) with HBA-enhanced MRI, with a significant difference in sensitivity but not specificity (P = .009 and P = .42, respectively). Interobserver agreements for the LI-RADS TRA were substantial for both CT and HBA-enhanced MRI (κ, 0.69 for both). Conclusion In patients who underwent local-regional therapy for hepatocellular carcinoma before liver transplant, hepatobiliary agent-enhanced MRI was more sensitive than CT in evaluating tumor viability with the Liver Imaging Reporting and Data System, version 2018, treatment response algorithm. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Bashir and Mendiratta-Lala in this issue.

10.
Molecules ; 26(4)2021 Feb 05.
Article in English | MEDLINE | ID: mdl-33562835

ABSTRACT

Natural products have continued to offer tremendous opportunities for drug development, as they have long been used in traditional medicinal systems. SHP2 has served as an anticancer target. To identify novel SHP2 inhibitors with potential anticancer activity, we screened a library containing 658 natural products. Polyphyllin D was found to selectively inhibit SHP2 over SHP1, whereas two other identified compounds (echinocystic acid and oleanolic acid) demonstrated dual SHP1 and SHP2 inhibition. In a cell-based assay, polyphyllin D exhibited cytotoxicity in Jurkat cells, an acute lymphoma leukemia cell line, whereas the other two compounds were ineffective. Polyphyllin D also decreased the level of phosphorylated extracellular signal-regulated kinase (p-ERK), a proliferation marker in Jurkat cells. Furthermore, knockdown of protein tyrosine phosphatase (PTP)N6 (SHP1) or PTPN11 (SHP2) decreased p-ERK levels. However, concurrent knockdown of PTPN6 and PTPN11 in Jurkat cells recovered p-ERK levels. These results demonstrated that polyphyllin D has potential anticancer activity, which can be attributed to its selective inhibition of SHP2 over SHP1.

11.
J Med Internet Res ; 23(1): e19625, 2021 01 21.
Article in English | MEDLINE | ID: mdl-33475514

ABSTRACT

BACKGROUND: With the rapid development of information and communication technologies, smart homes are being investigated as effective solutions for home health care. The increasing academic attention on smart home health care has primarily been on the development and application of smart home technologies. However, comprehensive studies examining the general landscape of diverse research areas for smart home health care are still lacking. OBJECTIVE: This study aims to determine the intellectual structure of smart home health care in a time series by conducting a coword analysis and topic analysis. Specifically, it investigates (1) the intellectual basis of smart home health care through overall academic status, (2) the intellectual foci through influential keywords and their evolutions, and (3) intellectual trends through primary topics and their evolutions. METHODS: Analyses were conducted in 5 steps: (1) data retrieval from article databases (Web of Science, Scopus, and PubMed) and the initial dataset preparation of 6080 abstracts from the year 2000 to the first half of 2019; (2) data preprocessing and refinement extraction of 25,563 words; (3) a descriptive analysis of the overall academic status and period division (ie, 4 stages of 3-year blocks); (4) coword analysis based on word co-occurrence networks for the intellectual foci; and (5) topic analysis for the intellectual trends based on latent Dirichlet allocation (LDA) topic modeling, word-topic networks, and researcher workshops. RESULTS: First, regarding the intellectual basis of smart home health care, recent academic interest and predominant journals and research domains were verified. Second, to determine the intellectual foci, primary keywords were identified and classified according to the degree of their centrality values. Third, 5 themes pertaining to the topic evolution emerged: (1) the diversification of smart home health care research topics; (2) the shift from technology-oriented research to technological convergence research; (3) the expansion of application areas and system functionality of smart home health care; (4) the increased focus on system usability, such as service design and experiences; and (5) the recent adaptation of the latest technologies in health care. Based on these findings, the pattern of technology diffusion in smart home health care research was determined as the adaptation of technologies, the proliferation of application areas, and an extension into system design and service experiences. CONCLUSIONS: The research findings provide academic and practical value in 3 aspects. First, they promote a comprehensive understanding of the smart home health care domain by identifying its multifaceted intellectual structure in a time series. Second, they can help clinicians discern the development and dispersion level of their respective disciplines. Third, the pattern of technology diffusion in smart home health care could help scholars comprehend current and future research trends and identify research opportunities based on upcoming research waves of newly adapted technologies in smart home health care.


Subject(s)
Bibliometrics , Health Services Research/methods , Home Care Services/standards , Humans
12.
Korean J Radiol ; 2020 Nov 03.
Article in English | MEDLINE | ID: mdl-33236540

ABSTRACT

OBJECTIVE: To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and its role as a second-line imaging modality after gadoxetate-enhanced MRI (Gd-EOB-MRI) in the diagnosis of hepatocellular carcinoma (HCC) among at risk observations. MATERIALS AND METHODS: We prospectively enrolled participants at risk of HCC with treatment-naïve solid hepatic observations (≥ 1 cm) of Liver Imaging Reporting and Data System (LR)-3/4/5/M during surveillance and performed Gd-EOB-MRI. A total of one hundred and three participants with 103 hepatic observations (mean size, 28.2 ± 24.5 mm; HCCs [n = 79], non-HCC malignancies [n = 15], benign [n = 9]; diagnosed by pathology [n = 57], or noninvasive method [n = 46]) were included in this study. The participants underwent CEUS with sulfur hexafluoride. Arterial phase hyperenhancement (APHE) and washout on Gd-EOB-MRI and CEUS were evaluated. The distinctive washout in CEUS was defined as mild washout 60 seconds after contrast injection. The diagnostic ability of Gd-EOB-MRI and of CEUS as a second-line modality for HCC were determined according to the European Association for the Study of the Liver (EASL) and the Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) guidelines. The diagnostic abilities of both imaging modalities were compared using the McNemar's test. RESULTS: The sensitivity of CEUS (60.8%) was lower than that of Gd-EOB-MRI (72.2%, p = 0.06 by EASL; 86.1%, p < 0.01 by KLCA-NCC); however, the specificity was 100%. By performing CEUS on the inconclusive observations in Gd-EOB-MRI, HCCs without APHE (n = 10) or washout (n = 12) on Gd-EOB-MRI further presented APHE (80.0%, 8/10) or distinctive washout (66.7%, 8/12) on CEUS, and more HCCs were diagnosed than with Gd-EOB-MRI alone (sensitivity: 72.2% vs. 83.5% by EASL, p < 0.01; 86.1% vs. 91.1% by KCLA-NCC, p = 0.04). There were no false-positive cases for HCC on CEUS. CONCLUSION: The addition of CEUS to Gd-EOB-MRI as a second-line diagnostic modality increases the frequency of HCC diagnosis without changing the specificities.

13.
Org Lett ; 22(21): 8419-8423, 2020 11 06.
Article in English | MEDLINE | ID: mdl-33074682

ABSTRACT

Antibody-drug conjugates (ADCs) in current clinical usage have been constructed via the nonspecific conjugation of drugs to antibodies, rendering the manufacturing processes difficult. In this study, a high-affinity IgG Fc-binding peptide equipped with a photoreactive amino acid was developed and successfully conjugated to Glu-382 of trastuzumab in a site-specific manner. The resulting conjugate was employed to generate a DAR 2 ADC product using click chemistry.

14.
Ultrasound Q ; 36(3): 224-234, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32890325

ABSTRACT

Contrast-enhanced ultrasound can be used effectively to evaluate focal hepatic lesions and offers unique advantages over computed tomography and magnetic resonance imaging. Serial vascular filling patterns of focal hepatic lesions during arterial, portal, and late phases can provide unique information on lesion characterization and differentiation. Sensitive depiction of arterial hypervascularity and analysis of washout pattern are clues for differentiation of several indeterminate hepatic nodules on conventional ultrasound and computed tomography/magnetic resonance. In this report, we present cases demonstrating clinical applications of contrast-enhanced ultrasound in the diagnosis and management of focal hepatic lesions.

15.
Radiology ; 297(1): 108-116, 2020 10.
Article in English | MEDLINE | ID: mdl-32749211

ABSTRACT

Background Perfluorobutane (PFB) and sulfur hexafluoride (SHF) have different physiologic characteristics, but it is unclear whether hepatocellular carcinomas (HCCs) show similar wash-in and washout patterns to both contrast agents at US. Purpose To investigate Contrast-Enhanced US Liver Imaging Reporting and Data System (LI-RADS) version 2017 HCC categorization by comparing PFB-enhanced US and SHF-enhanced US in participants at high risk for HCC. Materials and Methods In this prospective study conducted from February to August 2019, participants at high risk for HCC with treatment-naive hepatic observations (≥1 cm) categorized as LR-3, LR-4, LR-5, or LR-M (intermediate probability of HCC, probable HCC, definitely HCC, and probably malignant but not HCC specific, respectively) on cross-sectional images were screened. They underwent same-day PFB-enhanced US and SHF-enhanced US. Arterial phase hyperenhancement (APHE), washout time and degree, and echogenicity in the Kupffer phase (PFB-enhanced US) were evaluated and categorized by the operator using CEUS LI-RADS, who referred to the radiologist who performed the contrast-enhanced US, and by a reviewer. Diagnostic performance was analyzed using the McNemar test. Results Fifty-nine participants were evaluated (43 with HCC, 10 with non-HCC malignancies, six with benign findings). Nonrim APHE was identically observed in 95% (41 of 43, operator) or 88% (38 of 43, reviewer) of HCCs with both contrast agents. Among 43 HCCs, late (≥60 seconds) and mild washout were more frequent with PFB-enhanced US (34 with operator, 33 with reviewer) than with SHF-enhanced US (24 with operator, 26 with reviewer) (P = .04 or P = .12). The washout time for HCCs was later at PFB-enhanced US (median, 101 seconds ± 11) than at SHF-enhanced US (median, 84 seconds ± 5; P = .04). Sensitivity (34 of 43; 79%; 95% confidence interval [CI]: 64%, 90%) was higher with PFB-enhanced US than with SHF-enhanced US (23 of 43; 54%; 95% CI: 38%, 67%; P = .01). Specificity was 100% (95% CI: 79%, 100%) with both. Hypoenhancement in the Kupffer phase was more common in malignant (49 of 53 [92%] for both operator and reviewer) than in benign (two of six [33%] for operator, one of six [16%] for reviewer) lesions. Conclusion On the basis of the Contrast-Enhanced US Liver Imaging Reporting and Data System version 2017 algorithm, noninvasive US diagnosis of hepatocellular carcinoma by using perfluorobutane-enhanced US had higher diagnostic performance than sulfur hexafluoride-enhanced US, without loss of specificity. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kim and Jang in this issue.

16.
J Biomed Inform ; 109: 103516, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32736125

ABSTRACT

OBJECTIVE: The purpose of this study is to view research trends on surgery with mixed reality, and present the intellectual structure using bibliometric network analysis for the period 2000-2019. METHODS: Analyses are implemented in the following four steps: (1) literature dataset acquisition from article database (Web of Science, Scopus, PubMed, and IEEE digital library), (2) dataset pre-processing and refinement, (3) network construction and visualization, and (4) analysis and interpretation. Descriptive analysis, bibliometric network analysis, and in-depth qualitative analysis were conducted. RESULTS: The 14,591 keywords of 5897 abstracts data were ultimately used to ascertain the intellectual structure of research on surgery with mixed reality. The dynamics of the evolution of keywords in the structure throughout the four periods is summarized with four aspects: (a) maintaining a predominant utilization tool for training, (b) widening clinical application area, (c) reallocating the continuum of mixed reality, and (d) steering advanced imaging and simulation technology. CONCLUSIONS: The results of this study can provide valuable insights into technology adoption and research trends of mixed reality in surgery. These findings can help clinicians to overview prospective medical research on surgery using mixed reality. Hospitals can also understand the periodical maturity of technology of mixed reality in surgery, and, therefore, these findings can suggest an academic landscape to make a decision in adopting new technologies in surgery.

17.
Ultrasound Med Biol ; 46(11): 3046-3058, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32829983

ABSTRACT

The synergistic effects of a doxorubicin (Dox)-loaded microparticle-microbubble complex (DMMC) and focused ultrasound (FUS) with a short duty cycle (5%) were evaluated in a pancreatic cancer xenograft model established by inoculating immunodeficient mice with CFPAC-1 cells. The efficacy of the DMMC with FUS (study 1), the effect of conjugating the particles as opposed to mixing them (study 2) and the levels of tumor apoptosis and intracellular Dox (study 3) were evaluated. The DMMC with FUS exhibited the lowest tumor growth rate (30.8 mm3/wk) and the highest intracellular Dox uptake (8.8%) and tumor cell apoptosis rate (58.7%) among all treatments. DMMC had a significantly lower growth rate than the mixture of Dox-loaded microparticles and microbubbles (44.2 mm3/wk, p < 0.01) when they were combined with FUS. In conclusion, DMMC with short-duty-cycle FUS holds promise for tumor growth suppression, which may be attributed to high intracellular Dox uptake.

19.
Eur Radiol ; 2020 Aug 26.
Article in English | MEDLINE | ID: mdl-32845387

ABSTRACT

OBJECTIVES: To compare the diagnostic performances of first and second portal venous phases (PVP1 and PVP2) in revealing washout and capsule appearance for non-invasive HCC diagnoses in gadoxetic acid-enhanced MRI (Gd-EOB-MRI). METHODS: This retrospective study included 123 at-risk patients with 160 hepatic observations (HCCs, n = 116; non-HCC malignancies, n = 18; benign, n = 26) showing arterial phase hyper-enhancement (APHE) ≥ 1 cm at Gd-EOB-MRI. The mean time intervals from gadoxetic acid injection to PVP1 and PVP2 acquisitions were 53 ± 2 s and 73 ± 3 s, respectively. After evaluating image findings independently, imaging findings and diagnoses were finalized by a consensus of two radiologists using either PVP1 or PVP2 image sets according to the LI-RADS v2018 or EASL criteria. Sensitivity, specificity, and accuracy were compared. RESULTS: Among HCCs, more washout and enhancing capsule were observed in PVP2 (83.6% and 27.6%) than in PVP1 (50.9% and 19.8%) (p < 0.001, both). The PVP2 set presented significantly higher sensitivity (83.6% vs. 53.5%, LI-RADS; 82.8% vs. 50.0%, EASL; p < 0.001, both) and accuracy (0.88 vs. 0.73, LI-RADS; 0.88 vs. 0.72, EASL; p < 0.001, both) than the PVP1 set without significant specificity loss (93.2% vs. 93.2%, by LI-RADS or EASL; p = 0.32, both). None of the non-HCC malignancy was non-invasively diagnosed as HCC in both PVP image sets. CONCLUSION: Late acquisition of PVP detected washout and enhancing capsule of HCC more sensitively than early acquisition, enabling accurate diagnoses of HCC, according to LI-RADS or EASL criteria. KEY POINTS: • Among HCCs, more washout and enhancing capsules were observed in PVP2 than PVP1, quantitatively and qualitatively. • The portal venous phase acquired at around 70 s after contrast media administration (PVP2) provided significantly higher sensitivity and AUC value than PVP1 by using LI-RADS v2018 or EASL criteria. • More HCCs were categorized as LR-5 in PVP2 than in PVP1 images, and the specificity of PVP2 (93.5%) was comparable with PVP1 (93.5%).

20.
J Invest Surg ; : 1-8, 2020 Jul 20.
Article in English | MEDLINE | ID: mdl-32691637

ABSTRACT

INTRODUCTION: Remote ischemic preconditioning (rIPC) is a preventive strategy against ischemia-reperfusion injury. To reduce ischemia-reperfusion injury of random-pattern skin flaps, we investigated the therapeutic effects of rIPC combined with human adipose-derived stem cells (hADSCs) in a rat model. MATERIAL AND METHODS: In total, 24 female Sprague Dawley rats were divided into four groups (n = 6 each): control (skin flap only), rIPC, hADSCs, and rIPC + hADSCs. rIPC was performed in the hind limb of the rats over three cycles of 5 min of occlusion and 5 min of reperfusion, using a tourniquet. A rectangular (3 × 9 cm) dorsal skin flap was used. hADSCs (5 × 105 cells/100 µL) labeled with fluorescent dye were transplanted into the normal subcutaneous tissue at the skin flap boundary. After 14 days, the therapeutic effects of rIPC and hADSCs were evaluated via analysis of the necrotic flap area, histopathologic assessment, and immunohistochemistry (von Willebrand Factor (vWF) and CD31). RESULTS: The necrotic area of the skin flap significantly decreased in the rIPC + hADSCs group (32.75 ± 1.43%) compared with the control (40.60 ± 3.27%, P < 0.01) and rIPC groups (38.84 ± 0.77%, P < 0.05). Dye-labeled hADSCs migrated to the skin flap from the injection site. In the rIPC + hADSCs group, the epithelial tissue and skin appendage had regenerated, and the smooth muscle and subcutaneous fat layers were preserved. Many more vWF- and CD31-positive vessels were observed in the rIPC + hADSCs group compared with the other groups. CONCLUSIONS: The rIPC + hADSCs treatment appeared to reduce skin flap necrosis and activated neovascularization in rats. Therefore, it may be a good strategy for clinical treatment of ischemia-reperfusion injury.

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