Publications by authors named "Jung-Hoon Park"

148 Publications

Design and Usability Evaluations of a 3D-Printed Implantable Drug Delivery Device for Acute Liver Failure in Preclinical Settings.

Adv Healthc Mater 2021 Jul 23;10(14):e2100497. Epub 2021 Jun 23.

Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-Si, Gyeonggi-do, 14662, Republic of Korea.

Acute liver failure (ALF) requiring liver transplantation is a disease that occurs due to rapid hepatocellular dysfunction. As liver transplantation has various limitations, including donor scarcity, high cost, and immuno-incompatibility, continuous local delivery of biopharmaceuticals to the liver tissue can be a promising ALF treatment option. Here, the in vivo safety and usability of a 3D-printed implantable drug delivery device for effective ALF treatment is evaluated. The implantable reservoir consists of a 3D-printed container and a semipermeable membrane for repeated administrations of drugs, specifically to the liver tissue. The physical stability and function of the 3D-printed reservoir are confirmed by the mechanical properties and in vitro drug release test, respectively. In mice implanted with the reservoir system, mortality, weight changes, clinical signs, hematological and serum biochemical changes, and organ weight changes are not observed, suggesting no foreign body reaction. The usability of the reservoir system is further evaluated using an ALF model of 70% hepatectomized mice treated with N-acetylcysteine through the system, showing cell-specific regeneration and significant liver injury alleviation. Overall, the 3D-printed reservoir system is safe for studying the therapeutic potential of ALF treatment, and it can be used for the delivery of various active pharmaceutical ingredients.
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http://dx.doi.org/10.1002/adhm.202100497DOI Listing
July 2021

Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage.

J Control Release 2021 Jul 10;335:650-659. Epub 2021 Jun 10.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Division of Hepatobiliary Pancreas Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea; Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Electronic address:

Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.010DOI Listing
July 2021

Photothermal therapy via a gold nanoparticle-coated stent for treating stent-induced granulation tissue formation in the rat esophagus.

Sci Rep 2021 May 18;11(1):10558. Epub 2021 May 18.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Minimally invasive therapies using stent technology are currently limited by stent-induced granulation tissue formation adjacent to the stent. The effectiveness of photothermal therapy (PTT) using a gold nanoparticle (AuNP)-coated stent for treating stent-induced granulation tissue formation in the rat esophagus was investigated. All experiments were approved by the animal research committee of our institution. An AuNP-coated, self-expandable metallic stent (SEMS) was produced to conduct PTT under near-infrared laser irradiation. Forty rats were randomly divided into four groups (10 rats each). The animals in group A (non-coated SEMS) and group B (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) were sacrificed 4 weeks after stent placement. The rats in group C (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) and group D (AuNP-coated SEMS with local heating at 65 °C at 4 and 8 weeks) were sacrificed 8 weeks after stent placement. The effectiveness of local heating was assessed by histopathology. All procedures were successful in all of the animals. Seven rats were excluded because of stent migration (n = 2) and death (n = 5). Granulation tissue formation-related variables were significantly higher in group A than in groups B-D (all p < 0.05). Heat-shock protein 70 (HSP70) and TUNEL expression were significantly lower in group A than in groups B-D (all p < 0.05). Granulation tissue formation-related variables were significantly higher in group C than in groups B and D (all p < 0.05). PTT using AuNP-coated SEMS successfully treated granulation tissue formation after stent placement in the rat esophagus.
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http://dx.doi.org/10.1038/s41598-021-90182-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131374PMC
May 2021

Open-top axially swept light-sheet microscopy.

Biomed Opt Express 2021 Apr 25;12(4):2328-2338. Epub 2021 Mar 25.

Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea.

Open-top light-sheet microscopy (OT-LSM) is a specialized microscopic technique for high throughput cellular imaging of large tissue specimens including optically cleared tissues by having the entire optical setup below the sample stage. Current OT-LSM systems had relatively low axial resolutions by using weakly focused light sheets to cover the imaging field of view (FOV). In this report, open-top axially swept LSM (OTAS-LSM) was developed for high-throughput cellular imaging with improved axial resolution. OTAS-LSM swept a tightly focused excitation light sheet across the imaging FOV using an electro tunable lens (ETL) and collected emission light at the focus of the light sheet with a camera in the rolling shutter mode. OTAS-LSM was developed by using air objective lenses and a liquid prism and it had on-axis optical aberration associated with the mismatch of refractive indices between air and immersion medium. The effects of optical aberration were analyzed by both simulation and experiment, and the image resolutions were under 1.6µm in all directions. The newly developed OTAS-LSM was applied to the imaging of optically cleared mouse brain and small intestine, and it demonstrated the single-cell resolution imaging of neuronal networks. OTAS-LSM might be useful for the high-throughput cellular examination of optically cleared large tissues.
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http://dx.doi.org/10.1364/BOE.419030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086456PMC
April 2021

Local Heat Treatment for Suppressing Gastroduodenal Stent-Induced Tissue Hyperplasia Using Nanofunctionalized Self-Expandable Metallic Stent in Rat Gastric Outlet Model.

ACS Biomater Sci Eng 2020 04 19;6(4):2450-2458. Epub 2020 Mar 19.

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

Despite the promising results from the placement of covered or uncovered self-expandable metallic stent (SEMS) as a nonsurgical therapeutic option for the malignant gastric outlet obstruction (GOO), the long patency of the stent is still limited because of stent-induced tissue hyperplasia. Here, a local heat treatment using a nanofunctionalized SEMS is proposed for suppressing stent-induced tissue hyperplasia during GOO treatment. Highly efficient photothermal gold nanoparticle (GNP) transducer-coated SEMSs (GNP-SEMSs) were prepared for local heat treatment in rat gastric outlet. The in vivo heating temperature in rat gastric outlet model was evaluated and compared with in vitro heating temperature. Three groups of our developed 45 rat gastric outlet models were used: group A, noncoated SEMS only; group B, GNP-SEMS plus local heating; and group C, GNP-SEMS only to investigate in vivo efficacy of GNP-SEMS mediated local heating. Ten rats per group were sacrificed for 4 weeks, and five rats per group were sacrificed immediately after local heat treatment. The in vivo heating temperature was found to be 10.8% lower than the in vitro heating temperatures. GNP-SEMSs were successfully placed through a percutaneous approach into the rat gastric outlet ( = 45). The therapeutic effects of GNP-SEMS were assessed by histologic examination including hematoxylin-eosin, Masson trichrome, immunohistochemistry (TUNEL and CD31), and immunofluorescence (Ki67), and the results showed significant prevention of tissue hyperplasia following stent placement without adjacent gastrointestinal tissue damage. GNP-SEMS-mediated local heating could be an alternative therapeutic option for the suppression of tissue hyperplasia following stent placement in benign and malignant GOOs.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00307DOI Listing
April 2020

Dynamic multimodal holograms of conjugated organogels via dithering mask lithography.

Nat Mater 2021 Mar 4;20(3):385-394. Epub 2021 Jan 4.

School of Energy and Chemical Engineering, Department of Energy Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan Metropolitan City, Republic of Korea.

Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies.
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http://dx.doi.org/10.1038/s41563-020-00866-4DOI Listing
March 2021

The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique.

Cancer Res Treat 2021 Jul 15;53(3):733-743. Epub 2020 Dec 15.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.

Materials And Methods: RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.

Results: We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.

Conclusion: We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.
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http://dx.doi.org/10.4143/crt.2020.494DOI Listing
July 2021

Unilateral Bi-portal Endoscopic Decompression via the Contralateral Approach in Asymmetric Spinal Stenosis: A Technical Note.

Asian Spine J 2020 Nov 16. Epub 2020 Nov 16.

Department of Spinal Surgery, Daejeon Woori Hospital, Daejeon, Korea.

We discuss the technical details and operative advantages of approaching pathologies from the contralateral side in cases of asymmetric spinal stenosis. The contralateral approach offers better manipulative freedom and a more accessible target approach along the plane of the pathology, allowing safer decompression and facet preservation; further, this approach is ergonomic for surgeons. We recommend the adoption of this approach in decompressing asymmetric spinal stenosis.
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http://dx.doi.org/10.31616/asj.2020.0119DOI Listing
November 2020

Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma.

Ann Surg Oncol 2021 Jul 2;28(7):3983-3993. Epub 2020 Nov 2.

Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Seoul, Republic of Korea.

Background: Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20-50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence.

Methods: Tissues from 230 patients with resected stage I-II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan-Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model.

Results: Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02).

Conclusions: Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.
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http://dx.doi.org/10.1245/s10434-020-09276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184531PMC
July 2021

Dexmedetomidine as add-on sedation to reduce continuous infusion sedative use in mechanically ventilated patients.

Am J Health Syst Pharm 2021 02;78(Suppl 1):S1-S9

Division of Pulmonary, Critical Care & Sleep Medicine, University of California San Diego, La Jolla, CA.

Purpose: To characterize the impact of add-on dexmedetomidine therapy on baseline continuous infusion sedative use.

Methods: A retrospective, single-center, chart review-based study was conducted to assess outcomes of and potential predictors of response to add-on dexmedetomidine therapy in mechanically ventilated intensive care unit (ICU) patients who were already receiving continuous infusions of sedatives. Patients were defined as complete, partial, or nonresponders to add-on dexmedetomidine therapy if initial sedative infusion rates were reduced by 100%, by 50% to 99%, and by less than 50%, respectively, at 6 and 24 hours after initiation of dexmedetomidine.

Results: Among the 100 patients included in the study sample, there were 54 complete responders, 21 partial responders, and 25 nonresponders to dexmedetomidine add-on therapy at 6 hours after dexmedetomidine initiation; at 24 hours, there were 65 complete and 12 partial responders and 23 nonresponders. Of the variables tested (ie, baseline characteristics, opioid and antipsychotic use, hemodynamic parameters), none differentiated between complete or partial responders and nonresponders. Ventilator time, ICU length of stay (LOS), and hospital LOS after add-on dexmedetomidine therapy initiation were shorter among both partial responders and complete responders vs nonresponders (median, 1.1 days vs 4.1 days [P = 0.01], 7.0 days vs 14.1 days [P = 0.20], and 11.0 vs 17.0 days [P = 0.58], respectively), with only ventilator time being significantly different.

Conclusion: Add-on dexmedetomidine therapy can obviate or reduce the need for alternate sedation in as many as 75% of mechanically ventilated ICU patients. However, the addition of dexmedetomidine does not allow the reduction of alternate sedation in a substantial minority of patients, and failure to respond to dexmedetomidine can be identified as early at 6 hours after add-on therapy initiation. In the absence of clear predictors of response to dexmedetomidine, these data suggest empiric trials of dexmedetomidine can be considered but should be time-limited.
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http://dx.doi.org/10.1093/ajhp/zxaa327DOI Listing
February 2021

A Novel Intragastric Satiety-Inducing Device to Inhibit Weight Gain in Juvenile Pigs: a Pilot Study.

Obes Surg 2020 11 4;30(11):4643-4651. Epub 2020 Sep 4.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.

Background And Aims: Minimally invasive therapies for obesity are a bridge between lifestyle interventions and bariatric surgery. We developed a novel device to reduce weight gain rate and evaluated its safety and efficacy in juvenile pigs.

Methods: The intragastric satiety-inducing device (ISD) comprises a self-expandable esophageal metal stent connected to a star-shaped disc placed in the stomach fundus. Eight juvenile pigs were randomized into ISD (n = 5) and control (n = 3) groups. Body weight and serum ghrelin hormone were monitored weekly for 6 weeks. One pig was followed up for 4 additional weeks (rebound pig) after ISD removal. Histological examination and immunohistochemistry for the interstitial cells of Cajal (ICCs) were performed.

Results: ISD placement was successful in all pigs. Two ISDs (40%) migrated at 4 and 5 weeks after placement. Weight gain rates were significantly lower in the ISD group than in the control group from week 1 to 6 but were higher in the rebound pig than in a control pig from week 7 to 10. Mean ghrelin hormone level was higher in the control group than in the ISD group from week 1 to 6. ISD induced reversible inflammatory changes in the esophagus and stomach fundus. The number of ICCs was lesser in ISD pigs than in control and rebound pigs.

Conclusions: ISD placement is feasible and safe in juvenile pigs. It decreases weight gain rate but induces reversible inflammatory reaction and tissue hyperplasia. Its mechanism may be related to pressure exertion on the stomach fundus or gastric motility alteration.
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http://dx.doi.org/10.1007/s11695-020-04930-5DOI Listing
November 2020

Percutaneous antegrade removal of foreign bodies in the urinary tract: a 20-year, single-center experience.

Acta Radiol 2020 Aug 18:284185120950127. Epub 2020 Aug 18.

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

Background: While removing urinary tract foreign bodies is mostly performed through retrograde cystoscopy, antegrade removal using interventional procedures is reported less frequently.

Purpose: To evaluate the safety and effectiveness of percutaneous antegrade removal of urinary tract foreign bodies.

Material And Methods: A total of 14 consecutive patients (age range 9-80 years) who percutaneous antegrade removal of urinary tract foreign bodies between January 2001 and March 2020 were reviewed. Detailed removal procedures and complications were reviewed retrospectively.

Results: Types of foreign bodies were sheared percutaneous nephrostomy (PCN) catheters (n = 5), sheared double J stents (n = 3), migrated ureteral catheters (n = 3), embolization coils (n = 2), and a 0.018-inch guide wire (n = 1). The mean and median indwelling times (range 0-306 days) of the foreign bodies were 58.3 and 1.5 days, respectively. Computed tomography (CT) scans were conducted in six patients, and the extent and nature of the foreign bodies were well-visualized on CT scans. The removal access was new PCN access (n = 8), the tract missing PCN catheter (n = 3), pre-existing PCN access (n = 2), and percutaneous dissection (n = 1). The removal success rate was 92.9% (13/14) with either a simple (n = 8) or modified (n = 4; combination of a snare and guide wire is used) snare technique or a direct forceps grasp (n = 1). The mean procedure time for successful cases was 14.2 min (range 7-25 min). Procedure-related hematoma with (n = 2) or without (n = 1) renal pelvis injury occurred in three patients, which were all self-limited within one week.

Conclusion: Percutaneous antegrade removal is safe and effective for urinary tract foreign bodies.
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http://dx.doi.org/10.1177/0284185120950127DOI Listing
August 2020

Which Neighborhood Destinations Matter in the Asian Context? The Role of Destinations in Older Adults' Physical Activity and Sedentary Behaviors.

Biomed Res Int 2020 30;2020:8432934. Epub 2020 Jul 30.

Department of Health Promotion and Health Education, National Taiwan Normal University, 162, Heping East Road Section 1, Taipei 106, Taiwan.

Background: Neighborhood destinations play important roles in daily activity levels of older adults. However, little is known about how specific destinations are associated with these activities and/or sedentary behaviors, especially in Asia. This study investigated how neighborhood destinations were associated with physical activity recommendations and excessive sedentary time among older adults.

Methods: A telephone-based survey was conducted to collect cross-sectional data on the sociodemographic variables, residential neighborhoods, physical activities, and sedentary behaviors of 1,040 adults aged 65 years and above. Using data derived from Geographic Information Systems (GIS), an adjusted logistic regression was performed to examine the relationships between five neighborhood destination types (i.e., recreational facilities, utilitarian destinations, transit stops, temples, and schools) and both overall physical activity level and sedentary behavior.

Results: Significant interactions related to physical activity and sedentary behavior were observed based on both gender and neighborhood destinations. After adjusting for potential confounders, older men living in neighborhoods containing higher numbers of temples were more likely to achieve physical activity recommendations (OR = 1.85; 95% CI: 1.16-2.96). On the other hand, older women living in neighborhoods containing higher numbers of utilitarian destinations were more likely to engage in excessive sedentary time (OR = 1.70; 95% CI: 1.12-2.56).

Conclusions: In Asia, the presence of favorable local neighborhood temples may support physical activity levels for older men, while utilitarian destinations (which have previously been found to support activeness) may be related to excessive sedentary behaviors in older women.
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http://dx.doi.org/10.1155/2020/8432934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414340PMC
April 2021

Contralateral Keyhole Biportal Endoscopic Surgery for Ruptured Lumbar Herniated Disc: A Technical Feasibility and Early Clinical Outcomes.

Neurospine 2020 Jul 31;17(Suppl 1):S110-S119. Epub 2020 Jul 31.

Department of Neurosurgery, Daejeon Woori Hospital, Daejeon, Korea.

Objective: Spinal endoscopic surgery is increasingly adapted as a minimal invasive technique, however, significant facet joint violation may be developed after ipsilateral laminectomy. The aim of this study is to introduce surgical technique of contralateral keyhole biportal endoscopic surgery (CKES) for ruptured lumbar disc and report it is early surgical outcomes with facet joint violation.

Methods: Between January to December 2019, 27 patients with ruptured lumbar disc were underwent CKES. Simple radiographs were obtained to investigate development of iatrogenic instability or spondylolisthesis. Magnetic resonance imaging scan was checked about 8 hours after surgery to evaluate successful removal of ruptured disc and existence of facet joint violation. Clinical outcomes were assessed by modified MacNab criteria, visual analogue scale (VAS) scores of back and radicular pain.

Results: The mean age of the patients was 62.8 ± 12.48 years. The average operative time and mean follow-up period were 57.1 ± 21.36 minutes and 8.1 ± 3.78 months, respectively. Compared to preoperative scores, the VAS scores of back and radicular pain were significantly improved. Modified MacNab outcome grade was good to excellent in 96.3% (26 out of 27 patients) of patients. The reduction rate of facet joint plane was about 4.9% after contralateral approach.

Conclusion: CKES may be considered as an excellent surgical option to treat ruptured lumbar disc without the development of iatrogenic instability. Low rate of facet joint reduction, good visualization of lateral recess, and identification of accurate midline of central spinal canal are advantages of the procedure.
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http://dx.doi.org/10.14245/ns.2040224.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410376PMC
July 2020

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-analysis.

Surg Endosc 2021 Jul 17;35(7):3492-3505. Epub 2020 Jul 17.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave's syndrome (BS).

Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission.

Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8-5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2-7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2-6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1-3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1-3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD.

Conclusions: This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.
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http://dx.doi.org/10.1007/s00464-020-07806-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195755PMC
July 2021

Increasing the enhancement factor for DMD-based wavefront shaping.

Opt Lett 2020 Jul;45(13):3381-3384

Focusing through scattering media is a subject of great interest due to its direct impact in the field of biomedical optics. However, the greatest barrier currently limiting direct applications is the fact that most scattering media that we wish to deliver light through are dynamic. To focus or deliver light through dynamic scattering media, using a digital micromirror device (DMD) has been demonstrated to be a potential solution, as it enables fast modulation speeds. However, since a DMD is a binary amplitude modulator, the large number of controlled modes needed to acquire adequate focus enhancement has limited optimal usage. Here we demonstrate a novel (to the best of our knowledge) scheme to use the "thrown-away" components of light to effectively use a binary amplitude DMD as a binary phase modulator, thereby increasing the correction efficiency by a factor of two. Our concept can be applied to any iterative optimization algorithm and can speed up the iterative optimization process by increasing the enhancement factor, rather than the measurement or modulation speeds.
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http://dx.doi.org/10.1364/OL.394752DOI Listing
July 2020

Fast diffraction-limited image recovery through turbulence via subsampled bispectrum analysis.

Opt Lett 2019 Dec;44(24):5985-5988

Imaging through temporally changing aberrations is a common challenge that can be found in many different fields such as astronomy, long-range surveillance, and deep tissue bioimaging. Based on the notions originally developed in speckle interferometry, time-varying aberrations can be used to our advantage to obtain diffraction-limited resolution images through turbulence via bispectrum analysis. However, due to the heavy computational load brought on by the triple correlation and the phase extraction process, widespread use has been limited. Here, we demonstrate a Fourier domain subsampling scheme that can accelerate the speed of bispectrum analysis by more than 2 orders of magnitude. In contrast to other approaches for parallelization such as those based on Radon transform or image segmentation, our proposed method enables diffraction-limited imaging without suffering from resolution loss or image artifacts.
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http://dx.doi.org/10.1364/OL.44.005985DOI Listing
December 2019

Metallic Stent Mesh Coated with Silver Nanoparticles Suppresses Stent-Induced Tissue Hyperplasia and Biliary Sludge in the Rabbit Extrahepatic Bile Duct.

Pharmaceutics 2020 Jun 17;12(6). Epub 2020 Jun 17.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Recent therapeutic strategies to suppress restenosis after biliary stent placement are insufficient. Here, we demonstrate the usefulness of a self-expandable metal stent (SEMS), a stent mesh coated with silver nanoparticles (AgNPs), for suppression of both stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. The AgNP-coated SEMSs were prepared using a simple bio-inspired surface modification process. Then, the prepared SEMSs were successfully placed in 22 of 24 rabbits. Sludge formation in the AgNP-coated SEMS groups was significantly decreased compared to the control group on gross findings. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the AgNP-coated SEMS groups compared with the control group ( < 0.05 for all). There were no differences between the AgNP-coated SEMS groups ( > 0.05 for all). However, in the group coated with the greatest concentration of AgNPs (Group D), submucosal fibrosis was thicker than in the other AgNP-coated groups ( < 0.05 for all). The AgNP-coated metallic stent mesh significantly suppressed stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. Taken together, the AgNP coating strategy developed in this study could be widely utilized in non-vascular medical devices for anti-bacterial and anti-inflammatory responses.
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http://dx.doi.org/10.3390/pharmaceutics12060563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356520PMC
June 2020

Tumor Microenvironment Targeting Nano-Bio Emulsion for Synergistic Combinational X-Ray PDT with Oncolytic Bacteria Therapy.

Adv Healthc Mater 2020 07 11;9(13):e1901812. Epub 2020 Jun 11.

Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.

Various cancer therapies have been developed, but tumor recurrence with incomplete tumor killing and remaining tumor cells/tissues is frequent in monotherapies. Herein, a nano-bio therapeutic emulsion formulated with multifunctional nanoscintillators and anaerobic Clostridium novyi-NT spores for synergistic image-guided combinational cancer therapy is reported. MRI visible nanoscintillators (NSs) are synthesized with a NaGdF :Tb,[email protected] core/shell structure for an image-guided X-ray photodynamic therapy (PDT) of the normoxic peripheral tumor. An anaerobic oncolytic bacterium (C. novyi-NT) therapy is combined to treat the hypoxic central tumor tissues. Photosensitizer-coated NSs (PS-NSs) and C. novyi-NT spores are emulsified with clinically available ethiodized oil (Lipiodol) to be the nano-bio therapeutic emulsion and injected into the tumor with computed tomography image guidance. The distribution of nano-bio therapeutic emulsion, including PS-NSs and anaerobic C. novyi-NT spores in the tumor site, is confirmed by both X-ray and T -weighted magnetic resonance imaging. Following the image-guided X-ray PDT and anaerobic C. novyi- NT combination treatment, apoptotic cell death in cancer tissues, including both peripheral and central tumor regions, is significantly higher than in the control groups. This combination therapy approach using a nano-bio therapeutic emulsion is expected to overcome the limitations of conventional cancer therapy, resulting in increased cancer-therapeutic efficacy.
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http://dx.doi.org/10.1002/adhm.201901812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523430PMC
July 2020

Temporary percutaneous radiologic gastrojejunostomy with single gastropexy.

Acta Radiol 2021 Mar 9;62(3):329-333. Epub 2020 Jun 9.

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

Background: Although the effectiveness of percutaneous radiologic gastrojejunostomy (PRGJ) has been reported, a detailed description of the indications and clinical effectiveness of temporary PRGJ is still limited.

Purpose: To evaluate the clinical effectiveness and technical feasibility of temporary PRGJ using the modified Chiba-needle technique with single gastropexy.

Material And Methods: Temporary PRGJ using the modified Chiba-needle technique with single gastropexy was performed in 27 consecutive patients (19 men, 8 women; mean age = 61 years; age range = 32-77 years) for esophageal perforation (n = 18) or postoperative gastroparesis (n = 9). Outcomes analyzed included the technical and clinical success, procedure-related complications, and the tube indwelling period.

Results: Technical and clinical success was achieved in all 27 patients. All the tubes were electively removed 19-364 days (mean indwelling period = 104 days) after confirmation of the possibility of oral intake. Asymptomatic pneumoperitoneum occurred in 2/27 (7.4%) patients as minor complications and was resolved spontaneously by the time of the one-week follow-up. There were no major complications. During the follow-up period, a total of 11 tube changes were performed in seven patients for an elective tube change within a six-month interval (n = 5) or because of tube occlusion (n = 6).

Conclusion: Temporary PRGJ using the modified Chiba-needle technique with a single gastropexy was clinically effective and technically feasible in patients with esophageal perforation or gastroparesis. It can provide adequate enteral nutrition during its temporary placement.
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http://dx.doi.org/10.1177/0284185120929707DOI Listing
March 2021

High polymerase ε expression associated with increased CD8+T cells improves survival in patients with non-small cell lung cancer.

PLoS One 2020 20;15(5):e0233066. Epub 2020 May 20.

Macrogen Inc., Seoul, Republic of Korea.

DNA replicase polymerase ε (POLE) is critical in proofreading and correcting errors of DNA replication. Low POLE expression plays a pivotal role in accumulation of mutations and onset of cancer, contributing to development and growth of tumor cells. The aim of this study is to reveal the survival, alternative genes and antitumoral immune activities in non-small cell lung cancer (NSCLC) patients with low POLE expression and provide treatment strategies that can increase their survival rates. This study investigated the clinicopathologic parameters, various tumor-infiltrating lymphocytes (TILs), endogenous retrovirus, molecular interactions and in vitro drug screen according to POLE mutation/expression in 168 and 1,019 NSCLC patients from the Konkuk University Medical Center (KUMC) and the Cancer Genome Atlas, respectively. We identified mutations of 75 genes in the sequencing panels, with POLE frame shift p.V1446fs being the most frequent (56.8%) in KUMC based on 170 targeted sequencing panels. Mutant and high expression of POLE correlated with favorable prognosis with increased TILs and tumor mutation burden, compared with wild type and low expression of POLE. We found specific molecular interactions associated with cell cycle and antigen presentation. An in vitro drug screen identified dasatinib that inhibited growth of the NSCLC cell line with low POLE expression. POLE could contribute to the future development of anticancer drugs for patients with NSCLC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233066PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239475PMC
July 2020

Fast Magneto-Ionic Switching of Interface Anisotropy Using Yttria-Stabilized Zirconia Gate Oxide.

Nano Lett 2020 May 4;20(5):3435-3441. Epub 2020 May 4.

Center for Spintronics, Korea Institute of Science and Technology, Seoul 02792, Korea.

Voltage control of interfacial magnetism has been greatly highlighted in spintronics research for many years, as it might enable ultralow power technologies. Among a few suggested approaches, magneto-ionic control of magnetism has demonstrated large modulation of magnetic anisotropy. Moreover, the recent demonstration of magneto-ionic devices using hydrogen ions presented relatively fast magnetization toggle switching, ∼ 100 ms, at room temperature. However, the operation speed may need to be significantly improved to be used for modern electronic devices. Here, we demonstrate that the speed of proton-induced magnetization toggle switching largely depends on proton-conducting oxides. We achieve ∼1 ms reliable (>10 cycles) switching using yttria-stabilized zirconia (YSZ), which is ∼100 times faster than the state-of-the-art magneto-ionic devices reported to date at room temperature. Our results suggest that further engineering of the proton-conducting materials could bring substantial improvement that may enable new low-power computing scheme based on magneto-ionics.
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http://dx.doi.org/10.1021/acs.nanolett.0c00340DOI Listing
May 2020

EW-7197, a Transforming Growth Factor-Beta Type I Receptor Kinase Inhibitor, Ameliorates Acquired Lymphedema in a Mouse Tail Model.

Lymphat Res Biol 2020 10 27;18(5):433-438. Epub 2020 Feb 27.

Department of Biomedical Engineering Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Acquired lymphedema is a common consequence of cancer surgery. Fibrosis is one of the main causes of chronic lymphedema since it hinders lymphatic regeneration and this causes a significant decrease in lymphatic flow and accumulation of excessive protein-rich fluid. The transforming growth factor-β1 (TGF-β1) signaling pathway is known in a process of wound repair and fibrosis. In our study, the purpose was to evaluate the efficacy of EW-7197, a peroral TGF-β type I receptor kinase inhibitor, in treating acquired lymphedema. For lymphedema mouse tail model, we used 10- to 12-week-old female C57BL/6 mice. The skin was circumferentially excised, making a circular band followed by cauterization of lymphatic collecting vessels. Two groups were made in this study: control and treatment. The treatment group ( = 12) received a solution consisting of 0.1 mL of artificial gastric juice and 20 mg/kg EW-7197 by gavage once daily. For evaluation, tail diameter measurement, fluorescence lymphography, and immunofluorescence images were used. EW-7197 treatment ameliorates acquired lymphedema in a mouse tail model by increasing lymphangiogenesis and interstitial flow of the lymphatics by inhibition of the fibrosis. The differences in maximal tail thicknesses between the control and treatment groups were statistically significant from 2 to 4 weeks after surgery. The treatment group showed a greater number of lymphatic vessels at the surgery site than the control group. The treatment group also showed more FITC coverage area at the surgery site. EW-7197 treatment ameliorates acquired lymphedema in a mouse tail model by increasing lymphangiogenesis and interstitial flow.
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http://dx.doi.org/10.1089/lrb.2018.0070DOI Listing
October 2020

A Canine Model for Lymphangiography and Thoracic Duct Access.

Korean J Radiol 2020 03;21(3):298-305

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

Objective: To evaluate the technical feasibility of intranodal lymphangiography and thoracic duct (TD) access in a canine model.

Materials And Methods: Five male mongrel dogs were studied. The dog was placed in the supine position, and the most prominent lymph node in the groin was accessed using a 26-gauge spinal needle under ultrasonography (US) guidance. If the cisterna chyli (CC) was not opacified by bilateral lymphangiography, the medial iliac lymph nodes were directly punctured and Lipiodol was injected. After opacification, the CC was directly punctured with a 22-gauge needle. A 0.018-in microguidewire was advanced through the CC and TD. A 4-Fr introducer and dilator were then advanced over the wire. The microguidewire was changed to a 0.035-in guidewire, and this was advanced into the left subclavian vein through the terminal valve of the TD. Retrograde TD access was performed using a snare kit.

Results: US-guided lymphangiography (including intranodal injection of Lipiodol [Guerbet]) was successful in all five dogs. However, in three of the five dogs (60%), the medial iliac lymph nodes were not fully opacified due to overt Lipiodol extravasation at the initial injection site. In these dogs, contralateral superficial inguinal intranodal injection was performed. However, two of these three dogs subsequently underwent direct medial iliac lymph node puncture under fluoroscopy guidance to deliver additional Lipiodol into the lymphatic system. Transabdominal CC puncture and cannulation with a 4-Fr introducer was successful in all five dogs. Transvenous retrograde catheterization of the TD (performed using a snare kit) was also successful in all five dogs.

Conclusion: A canine model may be appropriate for intranodal lymphangiography and TD access. Most lymphatic intervention techniques can be performed in a canine using the same instruments that are employed in a clinical setting.
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http://dx.doi.org/10.3348/kjr.2019.0313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039726PMC
March 2020

A Novel Biodegradable Tubular Stent Prevents Pancreaticojejunal Anastomotic Stricture.

Sci Rep 2020 01 30;10(1):1518. Epub 2020 Jan 30.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Stricture of pancreatic-enteric anastomoses is a major late complication of a pancreaticoduodenectomy for the treatment of a periampullary tumor and can lead to exocrine and endocrine insufficiency such as malnutrition and diabetes mellitus. We investigated the safety and efficacy of a biodegradable tubular stent (BTS) for preventing a pancreaticojejunostomy (PJ) anastomotic stricture in both a rat and porcine model. The BTS was manufactured using a terpolymer comprising poly p-dioxanone, trimethylene carbonate, and glycolide. A cohort of 42 rats was randomized into 7 groups of 6 animals each after BTS placement into the duodenum for the biodegradation assay. A total of 12 pigs were randomized equally into a control and BTS placement group. The effectiveness of the BTS was assessed by comparing radiologic images with histologic results. Surgical procedures and/or BTS placements were technically successful in all animals. The median mass losses of the removed BTS samples from the rat duodenum were 2.1, 6.8, 11.2, 19.4, 26.1, and 56.8% at 1, 2, 3, 4, 6, and 8 weeks, respectively. The BTS had completely degraded at 12 weeks in the rats. In the porcine PJ model, the mean luminal diameter and area of the pancreatic duct in the control group was significantly larger than in the BTS group (all p < 0.05). BTS placement thus appears to be safe and effective procedure for the prevention of PJ anastomotic stricture. These devices have the potential to be used as a temporary stent placement to treat pancreatic-enteric anastomoses, but further investigations are required for optimization in human.
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http://dx.doi.org/10.1038/s41598-019-57271-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992790PMC
January 2020

Clinical effectiveness and safety of self-expanding metal stent placement following palliative chemotherapy in patients with advanced esophageal cancer.

Abdom Radiol (NY) 2020 02;45(2):563-570

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, 138-736, Republic of Korea.

Purpose: To investigate the effect of prior chemotherapy on self-expanding metal stent (SEMS)-related complications in patients with locally advanced primary esophageal cancer.

Materials And Methods: Data from patients with locally advanced primary esophageal cancer who received SEMS placement with or without prior chemotherapy were retrospectively reviewed. Patients were grouped according to prior palliative therapy: group A (n = 41) had received SEMS only, and group B (n = 64) had received palliative chemotherapy prior to SEMS placement. Patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement were evaluated. The overall patient cohort had a median follow-up period of 129 days (range 11-463). Outcomes after SEMS placement, including technical and clinical success rates, the occurrence of complications, and overall survival, were compared.

Results: There were no significant differences between the two groups regarding patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement. SEMS placement was technically successful in all patients, with no procedure-related complications reported. Clinical success was achieved in 95.1% of patients in group A and 96.8% of patients in group B. The duration of stent patency was significantly shorter in group B [162 days; 95% confidence interval (CI) 126.6-198.4 vs. group A (339 days; 95% CI 258.8-419.3], p = 0.001. No significant differences were seen between the two groups regarding dysphagia score improvement [group A (3.15 ± 0.57 to 1.17 ± 0.83; p < 0.001) and group B (3.17 ± 0.80 to 1.14 ± 0.79; p < 0.001); p = 0.66], complications [group A (10/41), and group B (24/64); p = 0.094], or overall survival [the median and mean overall survival periods were 105 (95% CI 30-180) and 132 days (95% CI 97-167), respectively, in group A, and 126 (95% CI 88-164) and 156 days (95% CI 132-180), respectively, in group B; p = 0.592].

Conclusion: Prior chemotherapy did not increase the risk of complications following SEMS placement in patients with locally advanced esophageal cancer. SEMS patency was significantly longer in patients who did not receive chemotherapy prior to SEMS placement.

Level Of Evidence: Level 4, Case Series.
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http://dx.doi.org/10.1007/s00261-019-02245-3DOI Listing
February 2020

Disordered Optics: Exploiting Multiple Light Scattering and Wavefront Shaping for Nonconventional Optical Elements.

Adv Mater 2020 Sep 25;32(35):e1903457. Epub 2019 Sep 25.

Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

Advances in diverse areas such as inspection, imaging, manufacturing, telecommunications, and information processing have been stimulated by novel optical devices. Conventional material ingredients for these devices are typically made of homogeneous refractive or diffractive materials and require sophisticated design and fabrication, which results in practical limitations related to their form and functional figures of merit. To overcome such limitations, recent developments in the application of disordered materials as novel optical elements have indicated great potential in enabling functionalities that go beyond their conventional counterparts, while the materials exhibit potential advantages with respect to reduced form factors. Combined with wavefront shaping, disordered materials enable dynamic transitions between multiple functionalities in a single active optical device. Recent progress in this field is summarized to gain insight into the physical principles behind disordered optics with regard to their advantages in various applications as well as their limitations compared to conventional optics.
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http://dx.doi.org/10.1002/adma.201903457DOI Listing
September 2020

Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics.

Biomaterials 2019 11 9;221:119418. Epub 2019 Aug 9.

Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13488, Republic of Korea. Electronic address:

Recently, natural killer (NK)-based immunotherapy has attracted attention as a next-generation cell-based cancer treatment strategy due to its mild side effects and excellent therapeutic efficacy. Here, we describe multifunctional nanoparticles (MF-NPs) capable of genetically manipulating NK cells and tracking them in vivo through non-invasive magnetic resonance (MR) and fluorescence optical imaging. The MF-NPs were synthesized with a core-shell structure by conjugation of a cationic polymer labeled with a near-infrared (NIR) fluorescent molecule, with the aid of a polydopamine (PDA) coating layer. When administered to NKs, the MF-NPs exhibited excellent cytocompatibility, efficiently delivered genetic materials into the immune cells, and induced target protein expression. In particular, the MF-NPs could induce the expression of EGFR targeting chimeric antigen receptors (EGFR-CARs) on the NK cell surface, which improved the cells' anti-cancer cytotoxic effect both in vitro and in vivo. Finally, when NK cells labeled with MF-NPs were injected into live mice, MF-NP-labeled NK cells could be successfully imaged using fluorescence and MR imaging devices. Our findings indicate that MF-NPs have great potential for application of NK cells, as well as other types of cell therapies involving genetic engineering and in vivo monitoring of cell trafficking.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119418DOI Listing
November 2019

Fluoroscopic Balloon Dilation Using a Flexible Guide Wire to Treat Obstructive Eustachian Tube Dysfunction.

J Vasc Interv Radiol 2019 Oct 10;30(10):1562-1566. Epub 2019 Aug 10.

Rehabilitation, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.

Purpose: To prospectively evaluate the midterm outcomes of fluoroscopic eustachian tube (E-tube) balloon dilation by using a flexible guide wire in patients with obstructive E-tube dysfunction.

Materials And Methods: From October 2016 to September 2017, adult outpatients with persistent otitis media who were unable to perform the Valsalva maneuver were prospectively enrolled. The analysis included 32 E-tubes from 31 patients (18 women, 13 men; mean age, 47 years old, range 25-72 years). Participants underwent fluoroscopic E-tube balloon dilation with a 0.035-inch flexible guide wire and a 6- × 20-mm balloon catheter. Clinical examinations to check for the ability to perform the Valsalva maneuver and otomicroscopy were conducted at 1 week and then at 1, 3, 12, and 18 months after the procedure.

Results: Balloon dilation was technically successful in all E-tubes. The mean time required for the procedure was 6.9 minutes (range, 5.8-10.3 minutes). The Valsalva maneuver was successful in opening 25 of 32 E-tubes (78.1%) at 3 months after balloon dilation. During the median follow-up of 15.9 months, failure of the Valsalva maneuver occurred in 4 of 25 improved E-tubes (16%), yielding a 2-year patency rate of 84%.

Conclusions: The fluoroscopic balloon dilation results were encouraging, and using a flexible guide wire for E-tube balloon dilation did not cause a false passage.
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http://dx.doi.org/10.1016/j.jvir.2019.04.041DOI Listing
October 2019

High prevalence of the MLH1 V384D germline mutation in patients with HER2-positive luminal B breast cancer.

Sci Rep 2019 07 29;9(1):10966. Epub 2019 Jul 29.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

HER2-positive luminal B breast cancer (BC), a subset of the luminal B subtype, is ER-positive and HER2-positive BC which is approximately 10% of all BC. However, HER2-positive luminal B BC has received less attention and is less represented in previous molecular analyses than other subtypes. Hence, it is important to elucidate the molecular biology of HER2-positive luminal B BC to stratify patients in a way that allows them to receive their respective optimal treatment. We performed molecular profiling using targeted next-generation sequencing on 94 HER2-positive luminal B BC to identify its molecular characteristics. A total of 134 somatic nonsynonymous mutations, including 131 nonsynonymous single nucleotide variants and three coding insertions/deletions were identified in 30 genes of 75 samples. PIK3CA was most frequently mutated (38/94, 40.4%), followed by TP53 (31/94, 33.0%), and others were detected at lower frequencies. Recurrent germline mutations of MLH1 V384D were found in 13.8% (13/94), with a significantly high TP53 mutations rate. The frequency of MLH1 V384D germline mutation in individuals with HER2-positive luminal B BC was significantly higher than that observed in the controls. All 13 cases were classified as microsatellite stable tumors. Tumor mutation burdens (TMB) were not significantly different between MLH1 V384D carrier and wild type. The concordant results of microsatellite instability (MSI) and TMB suggest that the haploinsufficiency of MLH1 plays a role as a tumor predisposition factor rather than a direct oncogenic driver. Our study identified, for the first time, that MLH1 V384D germline variant is frequently detected in HER2-positive luminal B BC. MLH1 V384D germline variant may not only contribute to gastrointestinal cancer predisposition but may also contribute to BC in East Asians.
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http://dx.doi.org/10.1038/s41598-019-47439-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662670PMC
July 2019
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