Publications by authors named "Hyo Jung Park"

92 Publications

Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.

Background & Aims: We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC).

Methods: Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed.

Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach.

Conclusions: In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach.
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http://dx.doi.org/10.1111/liv.15110DOI Listing
November 2021

Peptides Derived From S and N Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Induce T Cell Responses: A Proof of Concept for T Cell Vaccines.

Front Microbiol 2021 24;12:732450. Epub 2021 Sep 24.

Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, South Korea.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies has indicated the importance of T cell responses against this virus. In this study, we highlight the SARS-CoV-2 epitopes that induce potent T cell responses and discuss whether T cell responses alone are adequate to confer protection against SARS-CoV-2 and describe the administration of 20 peptides with an RNA adjuvant in mice. The peptides have been synthesized based on SARS-CoV-2 spike and nucleocapsid protein sequences. Our study demonstrates that immunization with these peptides significantly increases the proportion of effector memory T cell population and interferon-γ (IFN-γ)-, interleukin-4 (IL-4)-, tumor necrosis factor-α (TNF-α)-, and granzyme B-producing T cells. Of these 20 peptides, four induce the generation of IFN-γ-producing T cells, elicit CD8 T cell (CTL) responses in a dose-dependent manner, and induce cytotoxic T lymphocytes that eliminate peptide-pulsed target cells . Although it is not statistically significant, these peptide vaccines reduce viral titers in infected hamsters and alleviate pulmonary pathology in SARS-CoV-2-infected human ACE2 transgenic mice. These findings may aid the design of effective SARS-CoV-2 peptide vaccines, while providing insights into the role of T cells in SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fmicb.2021.732450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498111PMC
September 2021

Treatment Efficacy of Immune Checkpoint Inhibitors for Patients with Advanced or Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

J Clin Med 2021 Aug 16;10(16). Epub 2021 Aug 16.

Asan Medical Center, Department of Radiology and Research Institute of Radiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.

The treatment efficacy of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) has been reported heterogeneously across clinical trials. We conducted a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced/metastatic CRC. Ovid-Medline was searched to identify clinical trials providing the efficacy outcomes of overall response rate (ORR) or disease control rate (DCR). The pooled ORR and DCR were estimated across all studies and subgroups. Meta-regression was performed to find the influencing factors for treatment efficacy. A total of thirty studies (1870 patients) were eligible. The overall ORR and DCR were 20.1% and 58.5%, respectively, but these results were heterogeneous across studies. Multivariate meta-regression revealed that microsatellite phenotype (odds ratio of MSI-H/dMMR versus MSS/pMMR: 1.67, < 0.001) and drug regimen (odds ratio of monotherapy versus combination therapy: 1.07, = 0.019) were the source of heterogeneity and also significantly influenced factors for the efficacy of the treatment. Although the efficacy of ICIs as a first-line therapy was higher than that of ICIs as the second- or more-line therapy (ORR: 51.5% vs. 13.4%, DCR: 85% vs. 49.5%), multivariate regression showed that the line of therapy was not a significant factor for the treatment efficacy. Our study suggests that the microsatellite phenotype and drug regimen, rather than the line of treatment, are the primary factors influencing the treatment response among advanced/metastatic CRC patients treated with an ICI-based regimen.
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http://dx.doi.org/10.3390/jcm10163599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397178PMC
August 2021

Combined hydrocortisone, ascorbic acid, and thiamine therapy for septic shock with complicated intraabdominal infection: before and after cohort study.

Ann Surg Treat Res 2021 Jun 1;100(6):356-363. Epub 2021 Jun 1.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: The aim of this study was to assess the efficacy of intravenous hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in complicated intraabdominal infection (cIAI) patients with septic shock.

Methods: This was a single-center, retrospective before-after clinical study comparing clinical outcomes of cIAI patients with septic shock treated with HAT in a surgical intensive care unit (ICU). Delta modified sequential organ failure assessment (mSOFA) scores were evaluated to assess recovery of organ dysfunction. Additional outcomes included procalcitonin level change, daily vasopressor dosage, mean number of days free of mechanical ventilation in 28 days, and renal replacement therapy days.

Results: The delta mSOFA score (ICU admission mSOFA score minus 7th-day mSOFA score) was significantly higher in the HAT group than in the control group on the 7th day (2.30 -0.90, P = 0.003). The median 7-day change in procalcitonin score was higher in the control group than in the HAT group (5.94 10.72, P = 0.041). The difference in vasopressor score between the 1st day and the 4th day was significantly higher in the HAT group (17.63 9.91, P = 0.005).

Conclusion: In our study of cIAI in patients with septic shock, administration of HAT therapy may improve the recovery from organ dysfunction.
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http://dx.doi.org/10.4174/astr.2021.100.6.356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176196PMC
June 2021

Effective inactivated influenza vaccine for the elderly using a single-stranded RNA-based adjuvant.

Sci Rep 2021 06 7;11(1):11981. Epub 2021 Jun 7.

Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Gyeonggi-do, Republic of Korea.

There is an unmet need for new influenza vaccine strategies that compensate for impaired vaccine responses in elderly individuals. Here, we evaluated the effectiveness of a single-stranded RNA (ssRNA) as an adjuvant to enhance the efficacy of inactivated influenza vaccine (IIV) in mouse models. Immunization with the ssRNA along with IIV reduced viral titers as well as pathological and inflammatory scores in the lungs after influenza challenge in aged mice. ssRNA induced balanced Th1/Th2 responses with an increase in IgA titers. Moreover, the ssRNA adjuvant markedly increased the frequency of influenza HA-specific T cells and IFN-γ production along with the expression of genes related to innate and adaptive immune systems that could overcome immunosenescence in aged mice. Our findings indicate that ssRNA is an efficient vaccine adjuvant that boosts cellular and humoral immunity in aged mice, demonstrating its potential as a novel adjuvant for currently available influenza virus vaccines for elderly individuals.
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http://dx.doi.org/10.1038/s41598-021-91445-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184738PMC
June 2021

Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates.

Sci Adv 2021 05 28;7(22). Epub 2021 May 28.

Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.
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http://dx.doi.org/10.1126/sciadv.abg7156DOI Listing
May 2021

Value of discrepancy of the central scar-like structure between dynamic CT and gadoxetate disodium-enhanced MRI in differentiation of focal nodular hyperplasia and hepatocellular adenoma.

Eur J Radiol 2021 Jun 22;139:109730. Epub 2021 Apr 22.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Purpose: To identify the value of discrepancies in the central scar (CS)-like structure between dynamic CT and gadoxetate disodium-enhanced MRI for differentiating FNH from HCA.

Methods: This retrospective study included 113 patients with pathologically-diagnosed FNH (n = 80) or HCA (n = 37). CS-like structures were evaluated on arterial phase (AP) CT and hepatobiliary phase (HBP) MRI. Presence of the CS-like structure, its discrepancy in visibility or size between AP CT and HBP MRI and between AP and HBP MRI, and features of non-scarred tumor portion were evaluated by two radiologists. Inter-observer agreement was evaluated by intraclass correlation coefficients (ICCs) and weighted kappa. Univariable and multivariable logistic regression and ROC analysis were performed to explore features differentiating FNH from HCA.

Results: Inter-observer agreement was moderate-to-excellent (ICCs≥0.74, kappa≥0.65). On univariable analysis, presence of CS-like structures (P < 0.001), discrepancy of the CS-like structures between AP CT and HBP MRI (73.8 % in FNH; 16.2 % in HCA, P < 0.001) and between AP and HBP MRI (70.0 % in FNH; 16.2 % in HCA, P < 0.001), and the features of non-scarred tumor portion (P ≤ 0.011) were significantly different between FNH and HCA. On multivariable analysis, the discrepancy of CS-like structures between AP CT and HBP MRI, and the absence of low SI of the non-scarred tumor portion on HBP MRI, were suggestive of FNH (P = 0.036 and P < 0.001, respectively; area under the ROC curve, 0.96 [95 % CI, 0.93-0.99]).

Conclusion: Evaluation of discrepancy in the visibility or size of CS-like structures between dynamic CT and gadoxetate disodium-enhanced MRI may facilitate the differentiation of FNH from HCA.
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http://dx.doi.org/10.1016/j.ejrad.2021.109730DOI Listing
June 2021

Preoperative prediction of postsurgical outcomes in mass-forming intrahepatic cholangiocarcinoma based on clinical, radiologic, and radiomics features.

Eur Radiol 2021 Nov 23;31(11):8638-8648. Epub 2021 Apr 23.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Objectives: Current prognostic systems for intrahepatic cholangiocarcinoma (IHCC) rely on surgical pathology data and are not applicable to a preoperative setting. We aimed to develop and validate preoperative models to predict postsurgical outcomes in mass-forming IHCC patients based on clinical, radiologic, and radiomics features.

Methods: This multicenter retrospective cohort study included patients who underwent curative-intent resection for mass-forming IHCC. In the development cohort (single institution data), three preoperative multivariable Cox models for predicting recurrence-free survival (RFS) were constructed, including the clinical-radiologic, radiomics, and clinical-radiologic-radiomics (CRR) models based on clinical and CT findings, CT-radiomics features, and a combination of both, respectively. Model performance was evaluated in the test cohort (data from five institutions) using Harrell's C-index and compared with postoperative prognostic systems.

Results: A total of 345 patients (233, development cohort; 112, test cohort) were evaluated. The clinical-radiologic model included five independent CT predictors (infiltrative contour, multiplicity, periductal infiltration, extrahepatic organ invasion, and suspicious metastatic lymph node) and showed similar performance in predicting RFS to the radiomics model (C-index, 0.65 vs. 0.68; p = 0.43 in the test cohort). The CRR model showed significantly improved performance (C-index, 0.71; p = 0.01) than the clinical-radiologic model and demonstrated similar performance to the postoperative prognostic systems in predicting RFS (C-index, 0.71-0.73 vs. 0.70-0.73; p ≥ 0.40) and overall survival (C-index, 0.68-0.71 vs. 0.64-0.74; p ≥ 0.27) in the test cohort.

Conclusions: A model integrating clinical, CT, and radiomics information may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming IHCC.

Key Points: • The radiomics analysis had incremental value in predicting recurrence-free survival of patients with intrahepatic mass-forming cholangiocarcinoma. • The clinical-radiologic-radiomics model demonstrated similar performance to the postoperatively available prognostic systems (including 8th AJCC system) in predicting recurrence-free survival and overall survival. • The clinical-radiologic-radiomics model may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming intrahepatic cholangiocarcinoma.
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http://dx.doi.org/10.1007/s00330-021-07926-6DOI Listing
November 2021

CDISC-compliant clinical trial imaging management system with automatic verification and data Transformation: Focusing on tumor response assessment data in clinical trials.

J Biomed Inform 2021 05 9;117:103782. Epub 2021 Apr 9.

Clinical Platform Research Institute, C&R Research, Seoul, Republic of Korea.

Objective: Major issues in imaging data management of tumor response assessment in clinical trials include high human errors in data input and unstandardized data structures, warranting a new breakthrough IT solution. Thus, we aim to develop a Clinical Data Interchange Standards Consortium (CDISC)-compliant clinical trial imaging management system (CTIMS) with automatic verification and transformation modules for implementing the CDISC Study Data Tabulation Model (SDTM) in the tumor response assessment dataset of clinical trials.

Materials And Methods: In accordance with various CDISC standards guides and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, the overall system architecture of CDISC-compliant CTIMS was designed. Modules for standard-compliant electronic case report form (eCRF) to verify data conformance and transform into SDTM data format were developed by experts in diverse fields such as medical informatics, medical, and clinical trial. External validation of the CDISC-compliant CTIMS was performed by comparing it with our previous CTIMS based on real-world data and CDISC validation rules by Pinnacle 21 Community Software.

Results: The architecture of CDISC-compliant CTIMS included the standard-compliant eCRF module of RECIST, the automatic verification module of the input data, and the SDTM transformation module from the eCRF input data to the SDTM datasets based on CDISC Define-XML. This new system was incorporated into our previous CTIMS. External validation demonstrated that all 176 human input errors occurred in the previous CTIMS filtered by a new system yielding zero error and CDISC-compliant dataset. The verified eCRF input data were automatically transformed into the SDTM dataset, which satisfied the CDISC validation rules by Pinnacle 21 Community Software.

Conclusions: To assure data consistency and high quality of the tumor response assessment data, our new CTIMS can minimize human input error by using standard-compliant eCRF with an automatic verification module and automatically transform the datasets into CDISC SDTM format.
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http://dx.doi.org/10.1016/j.jbi.2021.103782DOI Listing
May 2021

Reduction of Visceral Adiposity as a Predictor for Resolution of Nonalcoholic Fatty Liver in Potential Living Liver Donors.

Liver Transpl 2021 10 26;27(10):1424-1431. Epub 2021 Jul 26.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

This study aimed to determine the factors associated with resolution of nonalcoholic fatty liver (NAFL) after lifestyle intervention in potential living liver donors as assessed by the gold standards in a longitudinal setting. This retrospective study included 115 potential living liver donors (mean age, 30.5 ± 7.5 years; 101 men) with NAFL who underwent paired liver biopsies and abdominal computed tomography (CT) examinations before and after lifestyle intervention between January 2011 and December 2018. Anthropometry, laboratory parameters, body composition, and hepatic steatosis (HS) were evaluated before and after lifestyle intervention. Anthropometry, laboratory parameters, body composition, and HS were significantly decreased after lifestyle intervention (all, P < 0.001). Relative changes in HS were weakly correlated with relative changes in the visceral fat area (VFA; r = 0.278; P = 0.003) and subcutaneous fat area (r = 0.382; P < 0.001), but not with body weight, body mass index, or skeletal muscle area. Patients with resolved NAFL after lifestyle intervention had significantly lower VFA at follow-up than those with persistent NAFL (mean ± standard deviation, 69.8 ± 39.1 versus 91.5 ± 41.4 cm ; P = 0.01). Multivariable logistic regression analysis demonstrated that the relative reduction of VFA (odds ratio per percent, 1.031; 95% confidence interval, 1.010-1.053; P = 0.004) was a significant independent factor associated with resolved NAFL after lifestyle intervention. In potential living liver donors with NAFL, the reduction of VFA is a significant factor associated with the resolution of NAFL after lifestyle intervention.
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http://dx.doi.org/10.1002/lt.26071DOI Listing
October 2021

Change in hepatic volume profile in potential live liver donors after lifestyle modification for reduction of hepatic steatosis.

Abdom Radiol (NY) 2021 08 25;46(8):3877-3888. Epub 2021 Mar 25.

Division of Liver Transplantation and Hepatobiliary Surgery, Departments of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Purpose: We aimed to evaluate changes in hepatic volume and hemiliver volume percentage in potential liver donors after hepatic steatosis (HS) reduction through lifestyle modification.

Methods: Fifty liver donor candidates with HS (macrovesicular fat [MaF] ≥ 20%) underwent abdominal computed tomography (CT) and liver biopsy before (baseline) and after (follow-up) lifestyle modification. According to the change in MaF, subjects were classified as group A (MaF reduction ≥ 20%, n = 25), and group B (MaF reduction < 20%, n = 25). The hepatic volume and hemiliver volume percentage were measured using CT volumetric analysis.

Results: Volume percentage of the left hemiliver + S1 (over the whole liver) significantly increased at follow-up in group A (P < 0.001) but not in group B (P = 0.598). The absolute volume change of the right hemiliver and its percentage change from the baseline were significantly greater than those of the left hemiliver + S1 in group A (P < 0.007). There were no significant differences in these values in group B (P = 0.064 and 0.507, respectively). The percentage of subjects that earned the benefit of becoming suitable donors from the change in hepatic volume distribution caused by HS improvement was 52.0% (13/25) and 40.0% (10/25) in group A and group B, respectively. Regarding posthepatectomy liver failure, none was identified in group A after donation, whereas 12% (3/25) was identified in group B.

Conclusion: Hepatic volume profile may change considerably in potential liver donors with HS (MaF ≥ 20%) after HS reduction through lifestyle modification. Reevaluation of the hepatic volume is required before liver procurement after lifestyle modification in these subjects.
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http://dx.doi.org/10.1007/s00261-021-03058-zDOI Listing
August 2021

Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

JAMA Netw Open 2021 03 1;4(3):e211136. Epub 2021 Mar 1.

University Hospitals Cleveland Medical Center, Department of Radiology, Case Western Reserve University, Cleveland, Ohio.

Importance: Hyperprogressive disease (HPD) is a recognized pattern of rapid tumor progression during immune checkpoint inhibitor (ICI) treatment. Definitions of HPD have not been standardized, posing the risk of capturing different tumoral behaviors.

Objectives: To provide a systematic summary of definitions and the incidence of HPD in patients undergoing ICI treatment and discuss the challenges of current assessment of HPD.

Data Sources: Articles that evaluated HPD published before March 3, 2020, were identified from MEDLINE and EMBASE.

Study Selection: Clinical trials and observational studies providing the incidence and definition of HPD from patients with cancer treated with ICIs.

Data Extraction And Synthesis: Factors included in the analysis comprised authors, year of publication, cancer type, ICI type, number of previous treatment lines, definition of HPD, time frame used to assess HPD, number of patients with HPD, onset of HPD, and prognosis of patients with HPD. Quantitative and qualitative syntheses for the incidence of HPD were performed.

Main Outcomes And Measures: Definitions of HPD were categorized and the range of incidence of HPD was evaluated. Subgroup analysis on the incidence of HPD according to the category was performed and the challenges associated with current HPD assessment were evaluated.

Results: Twenty-four studies with 3109 patients were analyzed. The incidence of HPD varied from 5.9% to 43.1%. The definitions were divided into 4 categories based on the calculation of tumor growth acceleration: tumor growth rate ratio (pooled incidence of HPD, 9.4%; 95% CI, 6.9%-12.0%), tumor growth kinetics ratio (pooled incidence, 15.8%; 95% CI, 8.0%-23.7%), early tumor burden increase (pooled incidence, 20.6%; 95% CI, 9.3%-31.8%), and combinations of the above (pooled incidence, 12.4%; 95% CI, 7.3%-17.5%). Hyperprogressive disease could be overestimated or underestimated if the assessment was limited to tumor growth rate or tumor growth kinetics ratio, target lesions, or response evaluation criteria in solid tumors (RECIST)-defined progressors, or if the assessment time frame conformed to RECIST. Study results on clinical outcome were heterogeneous on discriminating patients with HPD from those with natural progressive disease.

Conclusions And Relevance: Definitions of HPD appear to be diverse, with the incidence of HPD varying from 5.9% to 43.1% across studies examined in this meta-analysis. Varying incidence and definitions of HPD indicate the need for establishing its uniform and clinically relevant criteria based on currently available evidence.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.1136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991969PMC
March 2021

Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant pneumonia.

J Thorac Dis 2021 Feb;13(2):768-777

Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Vancomycin is the treatment of choice for serious methicillin-resistant (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25-30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome.

Methods: A retrospective cohort study was conducted on adult patients treated for MRSA pneumonia with vancomycin in medical intensive care units from April 2016 to August 2018. MRSA pneumonia was defined by the Centers for Disease Control and National Healthcare Safety Network definition. The primary outcome was the clinical cure of pneumonia. Secondary outcome measures included time to pharmacokinetic (PK) target attainment, microbiological cure, acute kidney injury, and all-cause mortality.

Results: A total of 81 patients were included; of these 22 (27.2%) received LD. The mean initial dose was significantly higher in the LD group. Clinical cure was similar in both groups (68.2% 66.1% in the LD and non-LD groups, respectively; P=0.860). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury. Furthermore, no difference was observed in terms of time to PK target attainment (69.2 63.4 h in the LD and non-LD groups, respectively; P=0.624). Vancomycin minimum inhibitory concentration of <2 mg/L was identified as an independent predictive factor for clinical cure in multivariable analysis, whereas vancomycin LD was not.

Conclusions: Initial LD is not associated with better clinical outcome or rapid pharmacological target attainment in critically ill patients with MRSA pneumonia. Further studies are warranted to provide better evidence for this widely recommended practice.
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http://dx.doi.org/10.21037/jtd-20-2243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947502PMC
February 2021

Radiomics and deep learning in liver diseases.

J Gastroenterol Hepatol 2021 Mar;36(3):561-568

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Recently, radiomics and deep learning have gained attention as methods for computerized image analysis. Radiomics and deep learning can perform diagnostic or predictive tasks using high-dimensional image-derived features and have the potential to expand the capabilities of liver imaging beyond the scope of traditional visual image analysis. Recent research has demonstrated the potential of these techniques in various fields of liver imaging, including staging of liver fibrosis, prognostication of malignant liver tumors, automated detection and characterization of liver tumors, automated abdominal organ segmentation, and body composition analysis. However, because most of the previous studies were preliminary and focused mainly on technical feasibility, further clinical validation is required for the application of radiomics and deep learning in clinical practice. In this review, we introduce the technical aspects of radiomics and deep learning and summarize the recent studies on the application of these techniques in liver radiology.
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http://dx.doi.org/10.1111/jgh.15414DOI Listing
March 2021

Effects of a comprehensive antimicrobial stewardship program in a surgical intensive care unit.

Int J Infect Dis 2021 Jul 24;108:237-243. Epub 2021 Feb 24.

Department of Critical Care Medicine and Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: We evaluated the effects of a comprehensive antimicrobial stewardship program (ASP) in a surgical intensive care unit (SICU).

Methods: The ASP was implemented from March 2018 to February 2019 at an SICU in a teaching hospital. An infectious disease physician and a pharmacist visited the SICU 3 times per week for prospective audit and feedback. Outcomes were compared between the ASP period and the same months in the preceding year (pre-ASP period). The primary outcome measure was the use of anti-pseudomonal beta-lactams (APBL). Appropriate antimicrobial de-escalation and ICU mortality rates were also compared.

Results: A total of 182 and 149 patients were included in the study for the pre-ASP and ASP periods, respectively. Although disease severity was higher in the ASP group (septic shock 39.0% in pre-ASP vs 65.1% in ASP group, P<0.001), the use of APBL as a definitive treatment was lower during ASP (68.7% vs 57.7%, OR 0.62, 95% CI 0.40-0.98). Appropriate antimicrobial de-escalation improved (63.2% vs 94.6%, P<0.001). ICU mortality was comparable (7.7% vs 7.4%) and significantly lower during the ASP, after adjustment (adjusted OR 0.41, 95% CI 0.18-0.92, P=0.032).

Conclusions: A comprehensive ASP decreased the use of APBL and was associated with improved patient outcomes.
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http://dx.doi.org/10.1016/j.ijid.2021.02.082DOI Listing
July 2021

Comparison of RECIST 1.1 and iRECIST in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Cancers (Basel) 2021 Jan 1;13(1). Epub 2021 Jan 1.

Department of Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA.

Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [ = 0.72]; pooled DCR, 45.3% and 48.7% [ = 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10-0.82 months; = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors.
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http://dx.doi.org/10.3390/cancers13010120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795764PMC
January 2021

Multidisciplinary intestinal rehabilitation in acute type II intestinal failure: Results from an intestinal rehabilitation team.

Asian J Surg 2021 Mar 28;44(3):549-552. Epub 2020 Nov 28.

Intestinal Rehabilitation Team, Samsung Medical Center, Sungkyunkwan University School of Medicine, South Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, South Korea.

Background: Type II (acute) intestinal failure (IF) is usually caused by complications of abdominal surgery resulting in enteric fistulas or proximal stomas and requires parenteral nutrition (PN) for several months. This study aimed to evaluate clinical management and outcome of type II IF patients in a single center.

Methods: Medical records of patients referred to the Intestinal Rehabilitation Team (IRT) at Samsung Medical Center (Seoul, Korea) were retrospectively analyzed.

Results: From 2014 to 2019, 34 patients with IF were referred. 28 patients were type II IF and were included in the analysis. There were 17 males and 11 females. Mean age of patients was 56.7 years. Pathophysiology of IF were high-output stoma in 16 cases, extensive bowel resection (with bowel in continuity) in 7 cases, and enterocutaneous fistula in 5 cases. The catastrophic events necessitating abdominal surgery in the patients were adhesive ileus in 9 cases, superior mesenteric artery thrombosis in 8 cases, internal herniation of bowel in 5 cases, traumatic bowel injury in 3 cases, and ischemic enteritis in 3 cases. Following medical and surgical rehabilitation, 10 patients (35.7%) were weaned off PN and overall mortality was 28.5%. Deaths were related to progression of underlying malignancies in 4 cases, liver failure in 3 cases, and sepsis in 1 case. Thirteen patients underwent surgery to restore bowel continuity. Six postoperative complications occurred in 4 patients (30.7%) and there were no postoperative mortalities.

Conclusion: Standardized care including restorative surgery resulted in successful outcomes in type II IF patients in this cohort.
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http://dx.doi.org/10.1016/j.asjsur.2020.11.010DOI Listing
March 2021

Fish Oil Monotherapy for Intestinal Failure-Associated Liver Disease on SMOFlipid in the Neonatal Intensive Care Unit.

J Clin Med 2020 Oct 23;9(11). Epub 2020 Oct 23.

Intestinal Rehabilitation Team, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.

Intestinal failure-associated liver disease (IFALD) is a life-threatening complication of parenteral nutrition (PN) and is most prevalent in the preterm neonatal population receiving long-term PN. In this study, we report the outcome of our experience with fish oil monotherapy for IFALD in a fish oil-based combination lipid emulsion administered to preterm low birth weight infants. Fasting neonates were administered as PN according to our center's nutrition protocol. A diagnosis of IFALD was made when the serum direct bilirubin levels were >2.0 mg/dL in two consecutive measurements that were more than one week apart, without evidence of intrinsic causes of liver dysfunction. The management of IFALD was conducted by switching the lipid emulsion from combination lipid emulsion to fish oil monotherapy at 1.0 g/kg/day, infused over 24 h. Fifteen infants met the criteria for IFALD and received fish oil monotherapy. The median gestational age was 27.5 weeks and the median birth weight was 862.5 g. IFALD was successfully reversed in 11 infants (11/15, 73.3%). The median duration of fish oil monotherapy was 39 days. Direct bilirubin values were initially elevated and then steadily declined from the third week of treatment onward. The enteral tolerance increased in varying degrees during the treatment period. The mean weight gain was 26.0 g/day during fish oil monotherapy. Omegaven (Fresenius Kabi Austria Gmbh, Graz, Austria) at a dose of 1.0 g/kg/day was well tolerated, and no adverse events related to Omegaven use were seen. The reversal of IFALD in preterm infants on combination lipid emulsion containing fish oil was achieved by switching to fish oil monotherapy.
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http://dx.doi.org/10.3390/jcm9113393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690741PMC
October 2020

Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Oncoimmunology 2020 06 19;9(1):1776058. Epub 2020 Jun 19.

Department of Radiology and Research Institute of Radiology, Asan Image Metrics, Asan Medical Center, Seoul, Republic of Korea.

Background: Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI.

Methods: NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8-12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models.

Results: Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months, .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months, < .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2-0.7) remained as a significant protective factor for mortality.

Conclusion: PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.
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http://dx.doi.org/10.1080/2162402X.2020.1776058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458612PMC
June 2020

Incidence of Pseudoprogression during Immune Checkpoint Inhibitor Therapy for Solid Tumors: A Systematic Review and Meta-Analysis.

Radiology 2020 10 4;297(1):87-96. Epub 2020 Aug 4.

From the Department of Radiology and Research Institute of Radiology, Asan Image Metrics, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea (H.J.P., K.W.K., C.H.S.); WHO Collaborating Center for Pharmaceutical Policy and Regulation, Department of Pharmaceutical Science, Utrecht University, Utrecht, the Netherlands (J.P.); Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea (S.Y.); Department of Radiology, Brigham and Women's Hospital, Boston, Mass (H.H., M.N.); and Department of Imaging, Dana-Farber Cancer Institute, Boston, Mass (M.N.).

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the incidence of pseudoprogression is critical for clinical practice.PurposeTo evaluate by systematic review and meta-analysis the incidence of pseudoprogression in cancer treatment with ICIs, and compare the incidence according to response criteria, tumor types, and immunotherapeutic agents.Materials and MethodsMedline and Embase were searched to identify relevant studies published before December 31, 2018. Clinical trials, post hoc analysis of clinical trials, and prospective studies on ICI treatment in patients with malignant solid tumors were included. Pooled incidence of pseudoprogression for all included studies, per definition of pseudoprogression, cancer type, and drug type, was obtained by random-effects models with inverse variance weighting model.ResultsSeventeen studies with 3402 patients were analyzed. The pooled incidence of pseudoprogression was 6.0% (95% confidence interval: 5.0%, 7.0%). The definition of pseudoprogression were divided into four categories: progressive disease followed by partial response (PR) or complete response (CR) but not stable disease (SD) with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (six studies); progressive disease followed by SD or PR or CR with RECIST 1.1 (five studies); progressive disease followed by SD or PR or CR with RECIST 1.0 (three studies); and progressive disease followed by SD or PR or CR with immune-related response criteria (irRC) (three studies). Incidence of pseudoprogression varied from 4.5% to 8.0% per definition, ranged from 5.0% to 7.0% per cancer type, and was 5.6% with the monotherapy of programmed cell death-1 inhibitor.ConclusionThe overall incidence of pseudoprogression was 6.0% and was less than 10% in subgroup analyses according to the definitions of pseudoprogression, cancer type, and immune checkpoint inhibitor type. Varying definitions across trials and studies indicates the need for uniform criteria of pseudoprogression for solid tumors.© RSNA, 2020See also the article by Dodd and MacDermott in this issue.
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http://dx.doi.org/10.1148/radiol.2020200443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526949PMC
October 2020

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection.

Vaccine 2020 09 29;38(39):6141-6152. Epub 2020 Jul 29.

Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea. Electronic address:

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4 and CD8 T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.
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http://dx.doi.org/10.1016/j.vaccine.2020.07.022DOI Listing
September 2020

MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice.

Pharmaceutics 2020 May 10;12(5). Epub 2020 May 10.

Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, Korea.

The effectiveness of vaccines is enhanced by adding adjuvants. Furthermore, the selection of an inoculation route depends on the type of adjuvant used and is important for achieving optimum vaccine efficacy. We investigated the immunological differences between two types of vaccines-spike protein from the Middle East respiratory syndrome virus and inactivated influenza virus vaccine, in combination with a single-stranded RNA adjuvant-administered through various routes (intramuscular, intradermal, and intranasal) to BALB/c mice. Intramuscular immunization with the RNA adjuvant-formulated spike protein elicited the highest humoral immune response, characterized by IgG1 and neutralizing antibody production. Although intranasal immunization did not elicit a humoral response, it showed extensive T-cell activation through large-scale induction of interferon-γ- and interleukin-2-secreting cells, as well as CD4+ T-cell activation in mouse splenocytes. Moreover, only intranasal immunization induced IgA production. When immunized with the inactivated influenza vaccine, administration of the RNA adjuvant via all routes led to protection after viral challenge, regardless of the presence of a vaccine-specific antibody. Therefore, the inoculation route should depend on the type of immune response needed; i.e., the intramuscular route is suitable for eliciting a humoral immune response, whereas the intranasal route is useful for T-cell activation and IgA induction.
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http://dx.doi.org/10.3390/pharmaceutics12050441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284860PMC
May 2020

Comparison between neuroendocrine carcinomas and well-differentiated neuroendocrine tumors of the pancreas using dynamic enhanced CT.

Eur Radiol 2020 Sep 28;30(9):4772-4782. Epub 2020 Apr 28.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objectives: To identify CT features distinguishing neuroendocrine carcinomas (NECs) of pancreas from well-differentiated neuroendocrine tumors (NETs) according to the World Health Organization 2017 and 2019 classification systems.

Methods: This retrospective study included 69 patients with pathologically confirmed pancreatic neuroendocrine neoplasms who underwent dynamic CT (17, 17, 18, and 17 patients for well-differentiated grade 1, 2, 3 NET and NEC, respectively). CT was used to perform qualitative analysis (component, homogeneity, calcification, peripancreatic infiltration, main pancreatic ductal dilatation, bile duct dilatation, intraductal extension, and vascular invasion) and quantitative analysis (interface between tumor and parenchyma [delta], arterial enhancement ratio [AER], portal enhancement ratio [PER], and dynamic enhancement pattern). Uni- and multivariate logistic regression analyses were performed to identify features indicating NEC. Optimal cutoff values for enhancement ratios were determined.

Results: NECs demonstrated significantly higher frequencies of main pancreatic ductal dilatation, bile duct dilatation, vascular invasion, and significantly lower delta (i.e., lower conspicuity), AER, and PER than well-differentiated NET (p < 0.05). On multivariate analysis, PER was the only independent factor selected by the model for differentiation of NEC from well-differentiated NET (odds ratio, < 0.001; 95% confidence interval [CI], < 0.001-0.012). PER < 0.8 showed the sensitivity of 94.1% (95% CI, 71.3-99.9) and the specificity of 88.5% (95% CI, 76.6-95.6). When three significant CT features were combined, the sensitivity and specificity for diagnosing NEC were 88.2% and 88.5%, respectively.

Conclusions: Tumor-parenchyma enhancement ratio in portal phase is a useful CT feature to distinguish NECs from well-differentiated NETs. Combining qualitative and quantitative CT features may aid in achieving good diagnostic accuracy in the differentiation between NEC and well-differentiated NET.

Key Points: • Neuroendocrine carcinoma of the pancreas should be distinguished from well-differentiated neuroendocrine tumor in line with the revised grading and staging system. • Neuroendocrine carcinoma of the pancreas can be differentiated from well-differentiated neuroendocrine tumor on dynamic CT based on assessment of the portal enhancement ratio, arterial enhancement ratio, tumor conspicuity, dilatation of the main pancreatic duct or bile duct, and vascular invasion. • Tumor-parenchyma enhancement ratio in portal phase of dynamic CT is a useful feature, which may help to distinguish neuroendocrine carcinoma from well-differentiated neuroendocrine tumor of the pancreas.
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http://dx.doi.org/10.1007/s00330-020-06867-wDOI Listing
September 2020

Weight-based vancomycin loading strategy may not improve achievement of optimal vancomycin concentration in patients with preserved renal function.

J Chemother 2021 Feb 23;33(1):56-61. Epub 2020 Apr 23.

Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

We performed a retrospective study to evaluate clinical effectiveness of vancomycin loading strategy and factors associated with achieving optimal . Patients administered vancomycin for ≥72 h from January to June 2018 were enrolled. Patients were divided into two groups: loading (LD) and non-loading (NLD). LD was defined as initial vancomycin dose ≥20 mg/kg and ≥120% of maintenance dose. During study period, 70 and 71 received initial LD (24.2 ± 2.5 mg/kg) and NLD (17.3 ± 3.3 mg/kg) doses of vancomycin, respectively ( < .001). Achievement of optimal was not different before administration of the third dose (24.4% in LD versus 18.2% in NLD,  = .484) and within 72 h (22.9% versus 28.2%,  = .759). Risk factors for failure to achieve optimal before administration of the third dose were higher creatinine clearance and higher level of serum albumin. Therefore, more sufficient loading or patient-specific dose strategies should be used to achieve optimal serum vancomycin .
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http://dx.doi.org/10.1080/1120009X.2020.1755590DOI Listing
February 2021

Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells.

Angew Chem Int Ed Engl 2020 07 8;59(28):11540-11549. Epub 2020 May 8.

Department of Biotechnology, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.

As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.
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http://dx.doi.org/10.1002/anie.202002979DOI Listing
July 2020

Practice of parenteral nutrition in hospitalized adult patients in Korea: A retrospective multicenter cross-sectional study.

PLoS One 2020 1;15(4):e0230922. Epub 2020 Apr 1.

Department of Pharmacy, Kyung Hee University Hospital at Kangdong, Seoul, Republic of Korea.

There have been no studies on the characteristics of parenteral nutrition (PN) supply for adult inpatients in South Korea. The aim of this retrospective multicenter cross sectional study was to investigate the current practice and characteristics of PN support in hospitalized adult patients in South Korea for the first time. This study was conducted retrospectively for the adult patients who were hospitalized and received PN in nine hospitals on August 1st, 2017 to October 30th, 2017. We evaluated the type of PN formulation, PN administration period, administration route, calories supplied, amount of protein supplied, and laboratory results. Among the 11,580 inpatient admissions on that day, 1,439 patients received PN (12.4%). The majority of enrolled patients (96.5%) used the commercial PN, of which 86.2% were multi-chamber. 71.2% of them received PN peripherally. The average in hospital PN duration was 17.8 ± 52.6 days. Patients received only 65.4 ± 25.4% calories of their target calories. The in-hospital mortality of enrolled patients was 22%. In South Korea, commercial PN was usually administered to hospitalized adult patients and in-hospital mortality in adult patients using PN was higher in South Korea compared to other countries. This study provides the characteristics and the PN support status of hospitalized adult patients receiving PN in South Korea.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230922PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112213PMC
July 2020

Reply to: "Non-enhanced magnetic resonance as a surveillance tool for hepatocellular carcinoma: Many unresolved issues".

J Hepatol 2020 07 27;73(1):213-214. Epub 2020 Mar 27.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2020.03.004DOI Listing
July 2020

Radiomics and Deep Learning: Hepatic Applications.

Korean J Radiol 2020 04;21(4):387-401

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Radiomics and deep learning have recently gained attention in the imaging assessment of various liver diseases. Recent research has demonstrated the potential utility of radiomics and deep learning in staging liver fibroses, detecting portal hypertension, characterizing focal hepatic lesions, prognosticating malignant hepatic tumors, and segmenting the liver and liver tumors. In this review, we outline the basic technical aspects of radiomics and deep learning and summarize recent investigations of the application of these techniques in liver disease.
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http://dx.doi.org/10.3348/kjr.2019.0752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082656PMC
April 2020

Reversal of Intestinal Failure-Associated Liver Disease by Increasing Fish Oil in a Multi-Oil Intravenous Lipid Emulsion in Adult Short Bowel-Syndrome Patients.

JPEN J Parenter Enteral Nutr 2021 01 17;45(1):204-207. Epub 2020 Mar 17.

Intestinal Rehabilitation Team, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Intestinal failure-associated liver disease (IFALD) is a serious complication of parenteral nutrition (PN). We report 2 cases of IFALD, which occurred in adult patients while on a regimen of multi-oil intravenous lipid emulsion containing fish oil.

Methods: Patients initially received PN containing 1-g/kg/d SMOFlipid 20% (SMOFlipid). When IFALD developed, lipid composition in PN was altered to include higher proportions of fish oil.

Results: Case 1 was a 23-year-old man with short-bowel syndrome. He had been fully dependent on PN for approximately 11 months with a direct bilirubin level of 15.1 mg/dL. Doses of 0.15-g/kg/d pure fish oil and 0.3-0.6-g/kg/d SMOFlipid were administered for 56 days, and IFALD was resolved 59 days after adding fish oil. Case 2 was an 85-year-old man who received extensive small-bowel resection because of internal herniation and small-bowel necrosis. He had elevated direct bilirubin levels and was diagnosed with IFALD. Fish-oil treatment was initiated after 50 days of receiving PN. The average daily amount of fish oil given was 0.14 g/kg/d. IFALD was resolved 44 days after adding Omegaven (Fresenius Kabi Austria Gmbh, Austria).

Conclusion: Two patients with advanced IFALD showed reversal of cholestasis by altering the lipid content of their PN to include more fish oil.
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http://dx.doi.org/10.1002/jpen.1823DOI Listing
January 2021

Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant.

Immun Inflamm Dis 2020 06 13;8(2):216-227. Epub 2020 Mar 13.

Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.

Introduction: Varicella-zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. A live attenuated vaccine (LAV) and glycoprotein E (gE) subunit vaccine were developed to prevent VZV-induced diseases. We recently reported that single-strand RNA (ssRNA) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (CrPV) is an effective adjuvant for protein-based and virus-like particle-based vaccines. Here, Chinese hamster ovary expression system and an LAV from Oka/SK strains.

Methods: We appraised the adjuvant effect of the same CrPV ssRNA encoding the gE gene formulated in the two vaccines using VZV-primed C57BL/6 mice and guinea pigs. Humoral immunity and cell-mediated immunity were assessed by enzyme-linked immunosorbent assay (ELISA) and ELISPOT in gE subunit vaccine and by ELISA and fluorescent antibody to membrane antigen in LAV.

Results: The gE subunit vaccine-induced gE-specific antibodies and CD4 T-cell responses (indicated by interferon-γ [IFN-γ] and interleukin-2 secretion) in the ssRNA-based adjuvant containing the VZV gE gene. Therefore, an ssRNA adjuvant combined with gE antigen can trigger the innate immune response and induce an adaptive immune response to ultimately activate humoral and cell-mediated responses. VZV LAV could also induce VZV-specific antibodies and IFN-γ stimulated by LAV, whereas the effect of ssRNA as a vaccine adjuvant could not be confirmed. However, the ssRNA adjuvant increased VZV-specific neutralizing antibody response.

Conclusions: Taken together, these results highlight that the gE subunit vaccine and LAV developed in this study can be functional VZV vaccines, and ssRNAs appear to function better as adjuvants in a subunit vaccine than in an LAV.
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http://dx.doi.org/10.1002/iid3.297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212201PMC
June 2020
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