Publications by authors named "Jeong Eun Kim"

433 Publications

Clinical application of 3D virtual and printed models for cerebrovascular diseases.

Clin Neurol Neurosurg 2021 May 29:106719. Epub 2021 May 29.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Objective: Three-dimensional (3D) printing techniques are rapidly advancing in the medical industry and in clinical practice. We aimed to evaluate the usefulness of 3D virtual and printed models of 6 representative cerebrovascular diseases using the software we developed.

Methods: Six cases consisted of 4 intracranial aneurysms (IAs) including complex ones with intrasaccular thrombosis, large size and a skull base location; 1 cavernous malformation in the pons; and 1 arteriovenous malformation in the parietal lobe. The 3D modeling process was performed retrospectively in 3 cases and prospectively in 1 IA. Segmentation of raw data and rendering and modification for 3D virtual models were processed mostly automatically.

Results: Most intracranial structures were satisfactorily made, including the skull, brain, vessels, thrombus, tentorium and major cranial nerves. Based on 3D modeling, surgical plan was changed in 1 prospective IA case. However, it was still difficult to discriminate small vessels and cranial nerves, to feel a realistic tactile sense and to directly perform presurgical simulations, such as dissection, removal, clipping and microanastomosis.

Conclusions: The 3D modeling was thought to be very helpful in experiencing the operative views from various directions in advance, in selecting an appropriate surgical approach, and in educating physicians and patients. With advancements in radiological resolution, processing techniques and material properties, 3D modeling is expected to simulate real brain tissues more closely.
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http://dx.doi.org/10.1016/j.clineuro.2021.106719DOI Listing
May 2021

Comparison of metabolic changes after neoadjuvant endocrine and chemotherapy in ER-positive, HER2-negative breast cancer.

Sci Rep 2021 May 18;11(1):10510. Epub 2021 May 18.

Department of Breast Surgery, University of Ulsan, College of Medicine, Asan Medical Center, 88 Olympic ro 43 gil, song pa gu, Seoul, 138-736, Korea.

Survival of breast cancer patients has improved, and treatment-related changes regarding metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivors. We sought to compare metabolic profile changes and the neutrophil-to-lymphocyte ratio (NLR) between patients undergoing neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) 3 years after the treatment. In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR. The mean age of patients was 42 years. The changes in BMI, serum glucose, and TC during NST and after 3 years were significantly different between NCT and NET. The proportion of overweight + obese group and the mean BMI were significantly increased during NCT (26.6% to 37.5%, 22.84 kg/m to 23.87 kg/m, p < 0.05), and these attributes found to have normalized at the 3-year follow-up. In the NET group, BMI changes were not observed (p > 0.05, all). There were no differences in changes over time among in the Hypertension group during NCT and NET (p = 0.96). The mean value of serum TC and fasting glucose significantly increased (< 0.05, both) during NCT and decreased 3 years after NCT (p < 0.05); however, no significant changes were observed in the NET group. The NLR was increased from 1.83 to 3.18 after NCT (p < 0.05) and decreased from 1.98 to 1.43 (p < 0.05) after NET. Compared with minimal metabolic effect of NET, NCT worsens metabolic profiles, which were recovered over 3 years. The NLR was increased after NCT but decreased after NET.
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http://dx.doi.org/10.1038/s41598-021-89651-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131718PMC
May 2021

"New classification of late and delayed complications after dermal filler: Localized or Generalized?"

J Cosmet Laser Ther 2021 May 6:1-9. Epub 2021 May 6.

Department of Dermatology, Hanyang University College of Medicine, Seoul, Korea.

As filler injections have become very common procedures worldwide, the number of complications has increased. However, there is a lack of systematized studies and precise classification of late and delayed complications. This study aimed to suggest new and reliable classifications and to characterize the clinical manifestations of late and delayed complications after filler injections. This retrospective study analyzed patients and suggested a new classification of delayed adverse effects related to filler injection. Several demographic and clinical findings were analyzed. Patients were classified into two types according to their clinical presentation: Type I (Localized) or Type II (Generalized). Twenty-five patients were evaluated during a clinically active adverse event suspected to be related to fillers. The most common injected filler substance was hyaluronic acid (HA, 68.8%). 76% of the patients were classified with Localized complications. In the Generalized complications group, systemic symptoms were more common (p=0.002), the treatment response was poor (p=0.010), and fewer patients showed complete remission (p=0.007) than in the Localized complications group. We propose a simple new classification method for late and delayed complications after dermal filler: Localized and Generalized. We expect that this new classification could help provide appropriate treatment and predict patient prognosis.
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http://dx.doi.org/10.1080/14764172.2021.1922703DOI Listing
May 2021

Undervaluation of Radiotherapy for Gross Desmoid Tumors: The Need for Absolute Volume Assessment.

In Vivo 2021 May-Jun;35(3):1777-1784

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

Background/aim: To compare absolute volume (AV) assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) for the response evaluation of desmoid tumors (DTs) treated with radiotherapy.

Patients And Methods: Eighteen patients with DTs ≥3 cm in size were included.

Results: The median follow-up duration was 78.0 months. Five patients achieved a complete response according to RECIST, seven reached a partial response (PR), and one eventually exhibited progression. The overall response rate was 61%, the median time to PR was 8.0 months. Six patients achieved stable disease, although three developed progressions. Of the six patients with a PR, the median change in maximum diameter was -46%, and the median change in maximum volume was -84%. Three patients could have been diagnosed with progression at least 6 months earlier if the AV increment was considered.

Conclusion: An AV assessment is essential for an accurate response assessment of DTs and radiotherapy seems feasible as a first-line treatment for DTs.
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http://dx.doi.org/10.21873/invivo.12437DOI Listing
January 2021

Characterization of submicron aerosols over the Yellow Sea measured onboard the Gisang 1 research vessel in the spring of 2018 and 2019.

Environ Pollut 2021 Apr 17;284:117180. Epub 2021 Apr 17.

Climate and Air Quality Research Department, National Institute of Environment Research, Incheon, Republic of Korea.

The physico-chemical properties of submicron aerosols were measured in the spring of 2018 and 2019 over the Yellow Sea onboard the Gisang 1 research vessel. Aerosol number concentrations in 2019 were slightly higher than those in 2018, and the mean number concentrations of particles larger than 10 nm and cloud condensation nuclei (CCN) at 0.6% supersaturation (S) in spring 2019 were 7312 ± 3807 cm and 4816 ± 1692 cm, respectively. Aerosol concentrations in June were lower than those in April and May, which was considered to be due to the East Asian summer monsoon. Aerosol number concentrations and size distributions were significantly influenced by meteorological conditions, such as wind and relative humidity. Aitken and accumulation mode particles dominated the aerosol number size distributions over the Yellow Sea. A distinct new particle formation (NPF) and growth event was observed, the spatial extent of which was estimated to cover at least 200 km × 400 km of the Yellow Sea. The general characteristics of NPF and growth over the Yellow Sea were similar to those in rural areas. Aerosol number concentrations below 1000 cm were recorded on extremely clean days. A CCN closure experiment conducted using previous measurement data showed good results, indicating that CCN concentrations can be estimated with good accuracy, and the hygroscopicity over the Yellow Sea was similar to that of aged continental aerosols.
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http://dx.doi.org/10.1016/j.envpol.2021.117180DOI Listing
April 2021

Final results of the randomized phase 2 LEO trial and bone protective effects of everolimus for premenopausal hormone receptor-positive, HER2-negative metastatic breast cancer.

Int J Cancer 2021 Apr 27. Epub 2021 Apr 27.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

The phase 2 LEO study showed that everolimus (EVE) plus letrozole (LET) with ovarian suppression increased progression-free survival (PFS) in tamoxifen-exposed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer with visceral metastases. Here we report final survival outcomes from the LEO study, and the results of exploratory analyses of bone turnover marker changes and bone-specific progressive disease. Patients who were exposed to or progressed on tamoxifen as adjuvant/palliative treatments were randomly assigned (2:1) to the EVE (leuprorelin + LET + EVE, n = 92) or LET (leuprorelin + LET, n = 45) arm. In a median 51-months of follow-up, the median PFS was 17.5 and 13.8 months in the EVE and LET arms, respectively (P = .245). Patients in the EVE arm with baseline visceral (median PFS 16.4 vs 9.5 months, P = .040) and bone (median PFS 17.1 vs 10.9, P = .003) metastases had greater PFS compared to the LET arm. No differences in overall survival (OS) were observed (median OS, 48.3 vs 50.8 months, P = .948). The 1-year cumulative incidences of bone-specific disease progression were 6.0% and 23.4% in the EVE and LET arms, respectively (hazard ratio 0.26, P < .001). Bone turnover markers at 6 and 12 weeks after treatment decreased in the EVE arm but were increased or stationary in the LET arm. Skeletal-related events occurred in 6.5% and 11.1% of patients in the EVE and LET arms, respectively. EVE + LET with ovarian suppression prolonged PFS in patients with baseline visceral or bone metastases and offered bone-protective effects in the overall study population. However, these clinical benefits did not translate into an OS benefit.
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http://dx.doi.org/10.1002/ijc.33613DOI Listing
April 2021

A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer.

Invest New Drugs 2021 Apr 7. Epub 2021 Apr 7.

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

Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m. No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017).
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http://dx.doi.org/10.1007/s10637-021-01110-9DOI Listing
April 2021

Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.

Sci Rep 2021 Mar 29;11(1):7118. Epub 2021 Mar 29.

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

There is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9-5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3-11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43-0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43-0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.
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http://dx.doi.org/10.1038/s41598-021-86482-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007566PMC
March 2021

High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer.

Exp Mol Med 2021 Mar 22;53(3):446-456. Epub 2021 Mar 22.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.

The global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher's exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.
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http://dx.doi.org/10.1038/s12276-021-00583-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080557PMC
March 2021

New formulas to predict the length of a peripherally inserted central catheter based on anteroposterior chest radiographs.

J Vasc Access 2021 Mar 22:11297298211001147. Epub 2021 Mar 22.

Department of Radiology, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, South Korea.

Purpose: To develop formulas that predict the optimal length of a peripherally inserted central catheter (PICC) from variables measured on anteroposterior (AP) chest radiography (CXR).

Materials And Methods: A total of 134 patients who underwent PICC insertion at the angiography suites were included. Clinical information such as patient height, weight, sex, age, cubital crease to inferior carina border length (CCL), and approach side were recorded. The following variables via measurement on AP-CXR were also collected: (1) distance from the T1 to T12 vertebra (DTV), (2) maximal horizontal thoracic diameter (MHTD), and (3) clavicle length (CL).

Results: Significant correlations between CCL and the following variables were identified in linear regression analyses: approach side, height, weight, sex, DTV, MHTD, and CL. Multiple regression results motivated the following two formulas: (1) with height data, estimated CCL (cm) = 12.429 + 0.113 × Height + 0.377 × MHTD (if left side, add 2.933 cm, if female, subtract 0.723 cm); (2) without height data, estimated CCL = 19.409 + 0.424 × MHTD + 0.287 × CL + 0.203 × DTV (if left side, add 3.063 cm, if female, subtract 0.997 cm). Estimated final PICC length can be calculated as (Estimated CCL, cm) + 4.0 (distance from inferior carina border to about 2.0 vertebra body unit, cm) - (distance from set cubital crease to designated puncture point, cm).

Conclusion: This study suggests new formulas to predict the appropriate PICC length for bedside insertion using previous AP-CXRs. With this formula, ideal positioning of the catheter's tip can be achieved in the clinical practice, avoiding or minimalizing the exposed catheter out of skin. These formulas may be helpful for patients who cannot undergo intra-hospital transport due to hemodynamic instability or who are concerned about isolation precautions due to any infectious-related contamination.
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http://dx.doi.org/10.1177/11297298211001147DOI Listing
March 2021

Therapeutic effects of a new invasive pulsed-type bipolar radiofrequency for facial erythema associated with acne vulgaris and rosacea.

J Cosmet Laser Ther 2020 Jul 2;22(4-5):205-209. Epub 2021 Mar 2.

Department of Dermatology, Hanyang University College of Medicine, Seoul, Korea.

Facial erythema from rosacea and acne is one of the most common problems encountered in dermatologic clinics. Effective therapeutic interventions for persistent erythema, which can cause patients frustration and psychological distress, are needed. The aim of this study was to evaluate the efficacy and safety of an invasive short pulsed-type bipolar radiofrequency device (IPBRF) for the treatment of intractable facial erythema. Thirty-one patients who had been diagnosed with rosacea or acne vulgaris and combined erythema underwent at least two IPBRF treatment sessions (maximum: 5) at 2-week intervals. Treatment outcomes were evaluated by investigator global assessment (IGA) based on clinical photographs, patient global assessment (PGA) score, and skin biophysical parameters including erythema index (EI), melanin index (MI), and transepidermal water loss (TEWL). Most patients showed significant clinical improvement. IGA scores for erythema, pores and smoothness improved after treatment. PGA also showed a trend toward improvement. Mean EI was significantly improved after the second treatment compared to baseline, which maintained until the study period. MI and TEWL showed a tendency toward improvement. There were no serious adverse events reported during the study. IPBRF led to rapid clinical improvement in facial erythema associated with rosacea and acne vulgaris and could be an effective and safe treatment option.
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http://dx.doi.org/10.1080/14764172.2021.1880599DOI Listing
July 2020

The Role and Clinical Effectiveness of Multiline Chemotherapy in Advanced Desmoplastic Small Round Cell Tumor.

Clin Med Insights Oncol 2021 17;15:1179554920987107. Epub 2021 Feb 17.

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

Background: A multimodal approach is the standard treatment for desmoplastic small round cell tumor (DSRCT); however, many patients are diagnosed with inoperable disease, which leaves chemotherapy as the only treatment option. There are limited data on the effectiveness of palliative chemotherapy, especially when used after first-line treatment. Here, we evaluated the clinical outcomes of patients with DSRCT treated with multiple lines of chemotherapy.

Methods: We reviewed medical records of 14 patients with pathologically confirmed DSRCT at Asan Medical Center between 2004 and 2018.

Results: The median age at diagnosis was 25, with males comprising 92.9% of patients. All patients had inoperable disease at presentation and received chemotherapy as the initial treatment. Four patients (28.6%) were treated with surgery, and complete resection was achieved in 1 patient. Median overall survival (OS) was 23.9 months, and 1-, 2-, and 3-year survival rates were 92.9%, 48.6%, and 19.5%, respectively. In patients receiving first- (N = 14), second- (N = 10), and third-line (N = 8) chemotherapy, median time-to-progression was 9.9, 3.5, and 2.5 months, respectively, and the disease control rates were 100%, 88.9%, and 75.0%, respectively. Factors associated with longer OS in the univariable analysis were ⩽2 metastatic sites at presentation (27.0 vs 14.7 months; = .024) and surgery with intended complete resection (43.5 vs 20.1 months; = .027).

Conclusions: Although advanced DSRCT may initially respond to chemotherapy after first-line treatment, the response becomes less durable as the disease progresses. Individualized treatment decisions focused on palliation should be made.
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http://dx.doi.org/10.1177/1179554920987107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894597PMC
February 2021

The Fate of Partially Thrombosed Intracranial Aneurysms Treated with Endovascular Intervention.

J Korean Neurosurg Soc 2021 May 26;64(3):427-436. Epub 2021 Feb 26.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.

Objective: The fate of partially thrombosed intracranial aneurysms (PTIAs) is not well known after endovascular treatment. The authors aimed to analyze the treatment outcomes of PTIAs.

Methods: We retrospectively reviewed the medical records of 27 PTIAs treated with endovascular intervention between January 1999 and March 2018. Twenty-one aneurysms were treated with intraluminal embolization (ILE), and six were treated with parent artery occlusion (PAO) with or without bypass surgery. Radiological results, clinical outcomes and risk factors for major recurrence were assessed.

Results: The initial clinical status was similar in both groups; however, the last status was better in the ILE group than in the PAO group (p=0.049). Neurological deterioration resulted from mass effect in one case and rupture in one after ILE, and mass effect in two and perforator infarction in one after PAO. Twenty cases (94.2%) in the ILE group initially achieved complete occlusion or residual neck status. However, 13 cases (61.9%) showed major recurrence, the major causes of which included coil migration or compaction. Seven cases (33.3%) ultimately achieved residual sac status after repeat treatment. In the PAO group, all initially showed complete occlusion or a residual neck, and just one case ultimately had a residual sac. Two cases showed major recurrence, the cause of which was incomplete PAO. Aneurysm wall calcification was the only significantly protective factor against major recurrence (odds ratio, 36.12; 95% confidence interval, 1.85 to 705.18; p=0.018).

Conclusion: Complete PAO of PTIAs is the best option if treatment-related complications can be minimized. Simple fluoroscopy is a useful imaging modality because of the recurrence pattern.
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http://dx.doi.org/10.3340/jkns.2020.0195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128530PMC
May 2021

First report of cucurbit chlorotic yellows virus infecting cucumber in South Korea.

Plant Dis 2021 Jan 6. Epub 2021 Jan 6.

Chungbuk National University, 34933, College of Agriculture, Life and Environment Sciences, Cheongju, Chungcheongbuk-do, Korea (the Republic of);

In October 2018, cucumber plants showing yellowing and chlorotic mottle symptoms were observed in a greenhouse in Chungbuk, South Korea. The observed symptoms were similar to those caused by cucurbit aphid-borne yellows virus (CABYV), which has been detected on cucumber plants in the region since it was reported on melon in Korea in 2015 (Lee et al 2015). To identify the potential agents causing these symptoms, 28 samples from symptomatic leaves and fruit of cucumber plants were subjected to total RNA extraction using the Plant RNA Prep Kit (Biocubesystem, Korea). Reverse transcription polymerase chain (RT-PCR) was performed on total RNA using CABYV specific primers and protocols (Kwak et al. 2018). CABYV was detected in 17 of the 28 samples, while 11 symptomatic samples tested negative. In order to identify the cause of the symptoms, RT-PCR was performed using cucurbit chlorotic yellows virus (CCYV) and cucurbit yellow stunting disorder virus (CYSDV) specific primers (Wintermantel et al. 2019). Eight of the 28 samples were positive using the CCYV specific primers while seven samples were infected with only CCYV and one contained a mixed infection of CABYV with CCYV. None of the samples tested positive for CYSDV. The expected 373 nt amplicons of CCYV were bi-directionally sequenced, and BLASTn analysis showed that the nucleotide sequences shared 98 to 100% identity with CCYV isolates from East Asia, including NC0180174 from Japan. Two pairs of primers for amplification of the complete coat protein and RNA-dependent RNA polymerase (RdRp) genes (Wintermantel et al., 2019) were used to amplify the 753bp coat protein and 1517bp RdRp genes, respectively. Amplicons of the expected sizes were obtained from a CCYV single infection and ligated into the pGEM T- Easy vector (Promega, WI, USA). Three clones from each amplicon were sequenced and aligned using Geneious Prime and found to have identical sequences (Genbank accession nos. MW033300, MW033301). The CP and RdRp sequences demonstrated 99% nucleotide and 100% amino acid identity with the respective genes and proteins of the CCYV isolates from Japan. This study documents the first report of CCYV in Korea. Since CCYV was first detected on melon in Japan, it has been reported in many other countries including those in East Asia, the Middle East, Southern Europe, North Africa, and recently in North America. CCYV has the potential to become a serious threat to production of cucurbit crops in Korea, particularly due to the increasing prevalence of the whitefly, , in greenhouse production systems. It will be important to continue monitoring for CCYV and determine potential alternate hosts in the region to manage and prevent further spread of CCYV in Korea.
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http://dx.doi.org/10.1094/PDIS-10-20-2254-PDNDOI Listing
January 2021

Leuprorelin combined with letrozole with/without everolimus in ovarian-suppressed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer: The LEO study.

Eur J Cancer 2021 Feb 31;144:341-350. Epub 2020 Dec 31.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Purpose: In the randomised phase II LEO trial, we investigated the effect of adding everolimus (EVE) to letrozole (LET) in ovarian-suppressed premenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2-) recurrent/metastatic breast cancer.

Methods: Patients with progression or prior exposure to tamoxifen with or without gonadotropin-releasing hormone agonists, either sequentially or concurrently, in adjuvant or metastatic setting were randomly assigned (2:1) to the EVE arm (leuprorelin + LET + EVE) or the LET arm (leuprorelin + LET) until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS). Secondary end-points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety.

Results: Between January 2014 and October 2018, 137 patients were enrolled (median age, 44 years [range, 24-56]). Of them, 75% had endocrine-sensitive disease, and 61% had visceral metastasis. With the median follow-up of 32.4 months, the median PFS was 18.1 months in the EVE arm and 13.8 months in the LET arm (HR 0.73, P = 0.137). Among patients with visceral metastases, the median PFS was significantly longer in the EVE arm (16.4 versus 9.5 months, P = 0.048). The median OS was not reached in both arms. The CBR was significantly higher in the EVE arm (83% versus 62%, P = 0.010). The ORR was similar between the two arms. The most common grade 3/4 adverse events in the EVE arm were neutropenia, alanine aminotransferase elevation and anaemia.

Conclusions: EVE plus LET with ovarian-suppression resulted in longer PFS in tamoxifen-exposed HR+, HER2- metastatic breast cancer patients with visceral metastasis.
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http://dx.doi.org/10.1016/j.ejca.2020.11.044DOI Listing
February 2021

First report of Tomato spotted wilt virus in in Korea.

Plant Dis 2020 Dec 17. Epub 2020 Dec 17.

Rural Development Administration, 54670, National Institute of Agricultural Sciences, Crop Protection, Jeonju, Jeollabuk-do, Korea (the Republic of);

Butterbur ( [Siebold & Zucc.] Maxim.) is a perennial herb of the Asteraceae family that is cultivated for medicinal and nutritional purposes. Due to long-term vegetative propagation of virus-infected native species, the yield and quality of butterbur plants have deteriorated. Five viruses have been reported to infect this species: alfalfa mosaic virus (AMV), arabis mosaic virus (ArMV), butterbur mosaic virus (ButMV), broad bean wilt virus 2 (BBWV-2), and cucumber mosaic virus (CMV) (Ham et al. 2016; Tochihara and Tamura 1976). From 2018 to 2019, butterbur plants in four greenhouses in Nonsan, South Korea (Supplementary Figure S1a, b) were found to show virus-like symptoms such as chlorotic and necrotic ring spots, necrosis, and mild mosaic on the leaves. Disease incidence was greater than 80% in one greenhouse (~1,000 m2). To identify the causal virus, we collected 17 symptomatic butterbur leaf samples from these greenhouses and performed reverse-transcription polymerase chain reaction (RT-PCR) analysis using species-specific detection primers for the five reported viruses and tomato spotted wilt virus (TSWV) (Supplementary Table S2). RT-PCR results showed that 12 samples from three greenhouses showing necrotic ring spots and mosaic symptoms were infected with a mixture of TSWV and ButMV, whereas 5 samples from one greenhouse showing mild mosaic symptoms were infected only with ButMV. TSWV (genus , family ) is transmitted by thrips and causes serious damage to a wide range of economically important plants (Pappu et al. 2009). ButMV (genus , family ) is transmitted by aphids, as well as infected vegetative propagation material (Hashimoto et al. 2009) and is the most predominant virus in butterbur in Korea (Ham et al. 2016). To isolate TSWV from butterbur, leaf extracts from symptomatic samples were mechanically inoculated on an assay host, , via three single-lesion passages followed by propagation in cv. Samsun. Thirty different indicator plant species were used for the bioassay of the TSWV isolate (TSWV-NS-BB20) by mechanical inoculation method (Supplementary Table S3). RT-PCR analysis confirmed that TSWV-NS-BB20 induced necrotic local lesions and mosaic on species and ring spots and mosaic on tomatoes and peppers. Notably, TSWV-NS-BB20 reproduced necrotic local lesions and mild mosaic symptoms on butterbur plants which were infected with ButMV with no obvious symptoms. To characterize TSWV-NS-BB20 genetically, the complete genome sequences of L (8914 nt), M (4751 nt), and S (2917 nt) RNA segments were obtained by RT-PCR using specific primers for TSWV as described previously (Kwak et al., 2020). The obtained sequences were deposited in GenBank under accession nos. MT643236, MT842841, and MN854654, respectively. BLASTn analysis showed that sequences of each segment had maximum nucleotide identities of 99.0, 98.9, and 98.6% to TSWV-L, M, and S (KP008128, FM163373, and KP008129) of TSWV-LL-N.05 isolate from tomato in Spain. Since 2018, TSWV outbreaks on butterbur are observed every year and thus may act as a potential source of TSWV infection for other crops of importance to Korea, such as pepper. Owing to the butterbur vegetative propagation, the identification of TSWV infection in butterbur will be helpful for future virus management to generate virus-free materials. To our knowledge, this is the first report of TSWV infection of butterbur.
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http://dx.doi.org/10.1094/PDIS-09-20-2027-PDNDOI Listing
December 2020

Relationship between disability self-awareness and cognitive and daily living function in schizophrenia.

Schizophr Res Cogn 2021 Mar 19;23:100192. Epub 2020 Nov 19.

Department of Psychiatry, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.

We investigated the relationship between disability self-awareness and cognitive and daily living functions in 49 patients with schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS) self-report was used to identify patient-rated global function. A clinician-rated measure of global function was obtained using the Personal and Social Performance Scale (PSP); disability self-awareness was calculated using two global function scores. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to evaluate clinical symptoms, while the MATRICS consensus cognitive battery (MCCB) and the UCSD Performance-based Skills Assessment (UPSA) were applied to assess cognitive and daily living functionality, respectively. The WHODAS scores correlated significantly with the MCCB verbal learning, visual learning, and social cognition domains, and with the UPSA communication domain. The PSP correlated significantly with all MCCB and UPSA domains. Disability self-awareness demonstrated positive correlation with most domains of MCCB and UPSA. The findings of this study indicate that the lower the cognitive and daily living function in patients with schizophrenia, the more positively they perceive their own disability.
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http://dx.doi.org/10.1016/j.scog.2020.100192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689331PMC
March 2021

First report of Mochi tree (Ilex integra) Anthracnose caused by Colletotrichum fioriniae in Korea.

Plant Dis 2020 Dec 1. Epub 2020 Dec 1.

Chungbuk National University, plant Medicine, Cheongju, Korea (the Republic of);

Ilex integra, also called Mochi tree, is an woody ornamental common in Asia, particularly in Korea, China, Japan, and Taiwan. Anthracnose, caused by Colletotrichum spp., is an economically important disease worldwide, affecting both fruit and seed quality. In April 2019, symptoms of Anthracnose were observed on leaves from several Mochi trees in an urban planting in Wando-gun, South Korea. Irregularly shaped, light-to-dark brown spots of 1-4mm were observed on young leaves. The lesions coalesced as each spot enlarged, flat and black fruiting bodies (acervuli) occurred on the brown lesions. Four symptomatic leaves were collected; fractions were cut from symptomatic tissue, including healthy tissue, then were disinfected with 1% sodium hypochlorite and 70% ethanol, and placed on potato dextrose agar (PDA). After dark-incubation at 25℃ for 7 days two isolates were obtained, the fungal colonies appeared as white to light gray mycelium, then becoming dark and orange to pink on the underside. After acervuli were produced on the plate, orange-red conidial masses erupted. Conidia observed from two isolates were hyaline, 1-celled, and oblong with round to acute apices, and measured 7 to 12 × 2 to 5 μm (mean ± SD: 9.29 ±2.26 × 3.68± 1.31 μm) (n=30). Genomic DNA was extracted and multi-locus sequencing was performed with one representative isolate using the internal transcribed spacer (ITS) (White et al. 1990), actin (ACT) genes, chitin synthase 1 gene (CHS-1) (Carbone and Kohn 1999), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Calmodulin (CAL) (Weir et al. 2012) and submitted. Blast search results showed that the isolate had 100%, 98.45%, 99.74%, 100%, and 100% nucleotide sequence identity with those of C. fioriniae (MT607651, MH717601, MG666441, MN895544, MN974144) respectively (Jamin and Mateu 2008). The five sequences were deposited in NCBI GenBank (Accession No: MT457472, MT465884, MT465885, MT465886, MT465887), which were assigned to ITS, ACT, CHS-1, GAPDH, and CAL regions, respectively. Based on the morphology (Shivas and Tan 2009) and molecular characterization (Guerber et al. 2003), the isolate was identified as C. fioriniae. To confirm pathogenicity, a conidial suspension (10⁶ conidia/ml) of the sequenced isolate was used to inoculated, young and mature leaves of a 4-year-old Mochi tree. Ten leaves of the seedling were disinfected with 70% ethanol, then were wounded with a toothpick. The conidial suspension (20 µl) was placed on the wound. The inoculated plant and control plants were tested with sterilized water and incubated at 25℃ in a moist chamber. The pathogenicity test was repeated three times. Typical spots were observed on the young leaves 2 days after inoculation, whereas they were observed on the mature leaves 7 days after inoculation. Acervuli developed on both young and mature leaves 5 and 20 days after treatment, respectively. The control plants did not show symptoms, and the fungus was re-isolated from the inoculated plant; thus, fulfilling Koch's Postulates. In Korea, C. fioriniae has been recorded as a pathogen of fruit (apple, eggplant and peach), but this is the first report of the fungus causing anthracnose on Mochi tree. The pathogen has been reported on leaves of a different Ilex species in the eastern USA (Farr and Rossman 2020). Although this new disease of I. integra is limited occurrence, C. fioriniae may be able to infect other plant species in South Korea.
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http://dx.doi.org/10.1094/PDIS-07-20-1559-PDNDOI Listing
December 2020

Effectiveness of Combining Bevacizumab With First-Line Chemotherapy Regimens for Metastatic Colorectal Cancer in Real-World Practice.

Clin Colorectal Cancer 2020 Oct 28. Epub 2020 Oct 28.

Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. Electronic address:

Background: Anti-vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting.

Patients And Methods: We retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy.

Results: In an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018).

Conclusion: The addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions.
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http://dx.doi.org/10.1016/j.clcc.2020.10.001DOI Listing
October 2020

HOS15 is a transcriptional corepressor of NPR1-mediated gene activation of plant immunity.

Proc Natl Acad Sci U S A 2020 12 16;117(48):30805-30815. Epub 2020 Nov 16.

Department of Biomedical Science and Engineering, Konkuk University, 05029 Seoul, South Korea;

Transcriptional regulation is a complex and pivotal process in living cells. HOS15 is a transcriptional corepressor. Although transcriptional repressors generally have been associated with inactive genes, increasing evidence indicates that, through poorly understood mechanisms, transcriptional corepressors also associate with actively transcribed genes. Here, we show that HOS15 is the substrate receptor for an SCF/CUL1 E3 ubiquitin ligase complex (SCF) that negatively regulates plant immunity by destabilizing transcriptional activation complexes containing NPR1 and associated transcriptional activators. In unchallenged conditions, HOS15 continuously eliminates NPR1 to prevent inappropriate defense gene expression. Upon defense activation, HOS15 preferentially associates with phosphorylated NPR1 to stimulate rapid degradation of transcriptionally active NPR1 and thus limit the extent of defense gene expression. Our findings indicate that HOS15-mediated ubiquitination and elimination of NPR1 produce effects contrary to those of CUL3-containing ubiquitin ligase that coactivate defense gene expression. Thus, HOS15 plays a key role in the dynamic regulation of pre- and postactivation host defense.
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http://dx.doi.org/10.1073/pnas.2016049117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720166PMC
December 2020

The role of postoperative radiotherapy after primary tumor resection in patients with de novo stage IV breast cancer.

Asia Pac J Clin Oncol 2020 Nov 11. Epub 2020 Nov 11.

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Aim: This study was undertaken to investigate the role of postoperative radiotherapy (PORT) including post-breast conserving radiotherapy (PBCRT) and post-mastectomy radiotherapy (PMRT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR).

Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS).

Results: At a median follow-up of 48.9 months (range, 3.5-183.4 months), the median OS was 54.9 months (range, 5.3-185.9 months) with a 5 year OS rate of 59.6%. Lower clinical T stage, Luminal A or B type tumors and PBCRT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. In multivariate analysis for LRRFS, the PBCRT arm demonstrated significant superiority compared to the No PORT arm. A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. PBCRT arm demonstrated significantly superior LRRFS of 100% while PMRT and No PORT arm demonstrated 81.5% and 84.0%, respectively CONCLUSIONS: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT, especially PBCRT was predictive of LRRFS, suggesting that patients may benefit from this treatment.
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http://dx.doi.org/10.1111/ajco.13506DOI Listing
November 2020

A split-face comparative trial of photopneumatic therapy versus intense pulsed light for the treatment of acne vulgaris.

J Cosmet Laser Ther 2020 Jul 18;22(4-5):185-189. Epub 2020 Oct 18.

Department of Dermatology, Hanyang University College of Medicine, Seoul, Republic of Korea.

A novel photopneumatic (PPX) technology, combining blue light-emitting diode (LED) and broadband intense pulsed light (IPL) with vacuum pressure, was developed for the treatment of acne vulgaris (AV). In this study, we enrolled 50 patients with mild to moderate AV. Five successive treatments were performed on one side of the face with a combined PPX device, and the opposite side was treated with only IPL with the same fluences at 2-week intervals. Clinical improvement was evaluated by inflammatory and non-inflammatory acne lesion counts. Additionally, patient self-assessment scores were assessed. The results showed that inflammatory and non-inflammatory acne lesion counts were significantly improved on both sides of the face after treatment ( < .001, = .001, respectively). Both inflammatory and non-inflammatory lesion counts were significantly reduced on the side treated with PPX when compared to the side treated with IPL alone ( = .008, = .045, respectively). Thirty-eight of 44 patients reported slight to moderate improvement on the patient self-assessment score. No significant side effect was observed during the study periods.In conclusion, PPX therapy is an effective and safe modality to treat mild to moderate AV. This study shows that PPX therapy has superior efficacy for the treatment of AV compared to IPL monotherapy.
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http://dx.doi.org/10.1080/14764172.2020.1827149DOI Listing
July 2020

Optimizing Nitrogen Balance Is Associated with Better Outcomes in Neurocritically Ill Patients.

Nutrients 2020 Oct 14;12(10). Epub 2020 Oct 14.

Department of Neurology, Seoul National University Hospital, Seoul 03080, Korea.

Marked protein catabolism is common in critically ill patients. We hypothesized that optimal protein supplementation using nitrogen balance might be associated with better outcomes in the neurointensive care unit (NICU) patients. A total of 175 patients admitted to the NICU between July 2017 and December 2018 were included. Nitrogen balance was measured after NICU admission and measurements were repeated in 77 patients. The outcomes were compared according to initial nitrogen balance results and improvement of nitrogen balance on follow-up measurements. A total of 140 (80.0%) patients had a negative nitrogen balance on initial assessments. The negative balance group had more events of in-hospital mortality and poor functional outcome at three months. In follow-up measurement patients, 39 (50.6%) showed an improvement in nitrogen balance. The improvement group had fewer events of in-hospital mortality ( = 0.047) and poor functional outcomes ( = 0.046). Moreover, improvement of nitrogen balance was associated with a lower risk of poor functional outcomes (Odds ratio, 0.247; 95% confidence interval, 0.066-0.925, = 0.038). This study demonstrated that a significant proportion of patients in the NICU were under protein hypercatabolism. Moreover, an improvement in protein balance was related to improved outcomes in neurocritically ill patients. Further studies are needed to confirm the relationship between protein balance and outcomes.
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http://dx.doi.org/10.3390/nu12103137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602201PMC
October 2020

Preoperative platelet count may predict postoperative symptomatic cerebral hyperperfusion syndrome after superficial temporal artery-middle cerebral artery anastomosis in moyamoya patients.

Clin Neurol Neurosurg 2020 12 2;199:106260. Epub 2020 Oct 2.

Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. Electronic address:

Objective: Platelets play a critical role in the inflammatory response, accompanied by microvascular endothelial dysfunction, underlying postoperative symptomatic cerebral hyperperfusion syndrome (PSCHS) after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in moyamoya patients. We examined whether the preoperative platelet count can predict PSCHS after STA-MCA anastomosis in such patients.

Methods: In 160 adult moyamoya patients undergoing 186 STA-MCA anastomoses, preoperative (demographics, initial clinical manifestation, and Suzuki grade), intraoperative (surgical time, operative side, fluid balance, and maximum and minimum mean blood pressure before and after vessel anastomosis), immediate postoperative (APACHE 2 score), and laboratory (hemoglobin and C-reactive protein levels and white blood cell and platelet counts) data were collected retrospectively.

Results: 84 patients (90 sides, 48.4 %) developed PSCHS with a median(IQR) onset of postoperative day 1(0-3) and duration of 4(3-7) days. The preoperative (25.2[22.8-28.0] vs. 23.1[19.7-26.2] ×10/μL, p = 0.009) platelet count was significantly higher in patients with PSCHS than in those without. The preoperative platelet count (odds ratio[95 % confidence interval], 1.14[1.03-1.27], p = 0.011), operation on the dominant hemisphere (6.84 [3.26-14.36], p < 0.001), and negative fluid balance (2.41[1.04-5.59], p = 0.040) were significant independent predictors of PSCHS. The optimal cut-off value for preoperative platelet count was 22.7 ×10/μL, and PSCHS developed more frequently in cases with a preoperative platelet count ≥ 22.7 × 10/μL (2.90[1.54-5.45]; p = 0.001).

Conclusion: A high preoperative platelet count may be associated with the development of PSCHS after STA-MCA anastomosis in adult moyamoya patients.
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http://dx.doi.org/10.1016/j.clineuro.2020.106260DOI Listing
December 2020

Evaluating waiting time with real-world health information in a high-volume cancer center.

Medicine (Baltimore) 2020 Sep;99(39):e21796

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine.

Wait time and scheduling for outpatient chemotherapy administration depends on various factors including infusion room hours of operation, availability of oncologists, nursing and pharmacy staffing, and physical space limitations. The aim of this study was to use the electronic event log of patients on health information system (HIS) to map and analyze patient flow in advanced metastatic colorectal patients at an academic cancer center. From January 2009 to December 2014, patients who were diagnosed with metastatic colorectal cancer and received outpatient chemotherapy confined to FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (folinic acid, fluorouracil, and oxaliplatin) were identified. From the HIS, patient flow was mapped by collection of event records including blood collection and pretreatment laboratory test, arrival to outpatient clinics, outpatient session (interview, drug accountability and appointment scheduling), and initiation of chemotherapy. A total of 10,638 patients were analyzed for 136,281 outpatient visits. The total office stay time from outpatient registration to initiation of chemotherapy was 92.58 ± 87.96 (mean ± standard deviation) minutes. Each outpatient session lasted 23.75 ± 51.55 minutes. After completing the outpatient session, patients waited 1,657.23 ± 3,027.65 minutes before chemotherapy and 46.66 ± 75.94 minutes within infusion room. Compared to the prior first come first serve rule, the new reservation system showed an improvement in overall waiting time from 2,432.3 ± 4,822.9 to 2,386.7 ± 143.4 minutes; however, waiting time within infusion room slightly increased from 36.68 ± 49.33 to 48.13 ± 46.32 minutes. Our findings indicate that transaction data analytics from HIS can be used to evaluate patient flow within oncology outpatient practice based on real-world hospital data.
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http://dx.doi.org/10.1097/MD.0000000000021796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523863PMC
September 2020

Predictive Role of TP53, PIK3CA and MLL2 in ER+ HER2+ Breast Bancer: Biomarker Analysis of Neo-ALL-IN [NCT 01275859].

Anticancer Res 2020 Oct;40(10):5883-5893

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

Background/aim: Somatic mutations were investigated in 21 patients with postmenopausal estrogen receptor (ER)-positive and human epidermal growth factor receptor-2 (HER-2)-positive (ER+HER2+) breast cancer (BC) treated with neoadjuvant letrozole and lapatinib, to identify their distinct molecular landscape.

Patients And Methods: We used tissue samples of 21 patients from phase II Neo ALL-IN cohort, and somatic alterations were examined using targeted exome sequencing performed in Foundation Medicine, Inc. (FMI).

Results: TP53 (61.9%) and PIK3CA (57.1%) were the two most frequently mutated genes that were inter-correlated (p=0.026). They were associated with unfavorable clinical outcomes, particularly when accompanying PIK3CA mutations at exon 9 in helical domains. Meanwhile, MLL2 alteration was negatively associated with mutations of TP53 or PIK3CA, and it tended to be present in patients with low KI-67 levels and no initial nodal involvement. Moreover, patients with MLL2 mutations numerically showed more favorable overall response rates (ORR) (80% vs. 56.2%) and better 5-year event-free survival (EFS) rates (100% vs. 87.5%) compared to the wild-type.

Conclusion: Mutations in TP53 and PIK3CA hotspot at exon 9 may be potential negative predictors of ER+HER2+ BC treated with neoadjuvant letrozole and lapatinib, while MLL2 inactivating mutation might confer therapeutic benefit in these patients.
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http://dx.doi.org/10.21873/anticanres.14608DOI Listing
October 2020

Patterns of recurrence in patients with curative resected rectal cancer according to different chemoradiotherapy strategies: Does preoperative chemoradiotherapy lower the risk of peritoneal recurrence?

Oncol Lett 2020 Nov 15;20(5):242. Epub 2020 Sep 15.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

The present study aimed to compare the pattern of distant recurrence between patients with non-metastatic rectal cancer treated with pre-operative (OP) and those treated with post-operative (post-OP) chemoradiotherapy (CRT). A total of 631 patients with newly diagnosed non-metastatic rectal cancer who had received pre-OP or post-OP CRT with curative intent surgery between August 2008 and April 2015 were identified. Inverse probability of treatment weighting (IPTW) was performed to account for baseline differences between the two arms. Overall, 449 and 182 patients were treated with pre-OP and post-OP CRT, respectively. Sex, tumor location, clinical tumor stage, CRT regimen and adjuvant chemotherapy regimen were significantly different between the two arms. The median follow-up duration was 55.4 months (range, 53.7-57.1). The 5-year distant recurrence-free survival (RFS) rates and 5-year overall survival (OS) rates were not significantly different between the pre-OP and post-OP CRT arms (RFS, 67.5 vs. 71.6%, P=0.595 and OS, 81.9 vs. 77.0%, P=0.449), and no difference was observed in the distant recurrence patterns. Following IPTW, there was still no difference in distant RFS (pre-OP vs. post-OP CRT; hazard ratio (HR)=0.62; P=0.911), but pre-OP CRT was significantly associated with lower peritoneal recurrence (pre-OP vs. post-OP CRT; HR, 0.13; P=0.032). In addition, there was no significant difference in OS between the two arms (pre-OP vs. post-OP CRT; HR, 0.85; P=0.665). In conclusion, although distant RFS was not significantly different between the two arms, pre-OP CRT was significantly associated with a lower risk of peritoneal recurrence than post-OP CRT in patients non-metastatic rectal cancer.
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http://dx.doi.org/10.3892/ol.2020.12105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509510PMC
November 2020

Surgical strategy for patients with supratentorial spontaneous intracerebral hemorrhage: minimally invasive surgery and conventional surgery.

J Cerebrovasc Endovasc Neurosurg 2020 Sep 21;22(3):156-164. Epub 2020 Sep 21.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objective: The role of surgery in spontaneous intracerebral hemorrhage (sICH) is still controversial. We aimed to investigate the effectiveness of minimally invasive surgery (MIS) compared to conventional surgery (CS) for supratentorial sICH.

Methods: The medical data of 70 patients with surgically treated supratentorial sICH were retrospectively reviewed. MIS was performed in 35 patients, and CS was performed in 35 patients. The surgical technique was selected based on the neurological status and radiological findings, such as hematoma volume, neurological status and spot signs on computed tomographic angiography. Treatment outcomes, prognostic factors and the usefulness of the spot sign were analyzed.

Results: Clinical states in both groups were statistically similar, preoperatively, and in 1 and 3 months after surgery. Both groups showed significant progressive improvement till 3 months after surgery. Better preoperative neurological status, more hematoma removal and intensive care unit (ICU) stay ≤7 days were the significant prognostic factors for favorable 3-month clinical outcomes (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.96, p=0.04; OR 1.04, 95% CI 1.01-1.08, p=0.02; OR 26.31, 95% CI 2.46-280.95, p=0.01, respectively). Initial hematoma volume and MIS were significant prognostic factors for a short ICU stay (≤7 days; OR 0.95; 95% CI 0.91-0.99; p=0.01; OR 3.91, 95% CI 1.03-14.82, p=0.045, respectively). No patients in the MIS group experienced hematoma expansion before surgery or postoperative rebleeding.

Conclusions: MIS was not inferior to CS in terms of clinical outcomes. The spot sign seems to be an effective radiological marker for predicting hematoma expansion and determining the surgical technique.
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http://dx.doi.org/10.7461/jcen.2020.22.3.156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522387PMC
September 2020

Revascularization Evaluation in Adult-Onset Moyamoya Disease after Bypass Surgery: Superselective Arterial Spin Labeling Perfusion MRI Compared with Digital Subtraction Angiography.

Radiology 2020 12 22;297(3):630-637. Epub 2020 Sep 22.

From the Departments of Radiology (I.H., R.E.Y., K.M.K., D.H.Y., T.J.Y., S.H.C., J..K., C.H.S.) and Neurosurgery (W.S.C., J.E.K.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea; and Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (S.H.C., J..K., C.H.S.).

Background A superselective (SS) arterial spin labeling (ASL) MRI technique can be used to monitor the revascularization area as a supplementary or alternative modality to digital subtraction angiography (DSA), with the advantage of being noninvasive. Purpose To evaluate whether SS-ASL perfusion MRI could be used to visualize the revascularization area after combined direct and indirect bypass surgery in adults with moyamoya disease compared with DSA. Materials and Methods Patients diagnosed with moyamoya disease who underwent DSA and SS-ASL 6 months after surgery between June 2017 and November 2019 in a single institution were retrospectively evaluated. Subjective grading of the revascularization area and collateral grading in 10 Alberta Stroke Program Early CT Score (ASPECTS) locations were performed. The change in perfusion status in a subgroup that underwent both preoperative and postoperative SS-ASL studies was evaluated. Intermodality agreement was analyzed by using weighted κ statistics. Results Thirty-seven hemispheres from 33 patients (mean age, 39 years ± 12 [standard deviation]; 20 women) were evaluated. The intermodality agreement of the revascularization area grading was substantial (weighted κ = 0.70; 95% confidence interval [CI]: 0.37, 1.00). The overall intermodality agreement of the postoperative collateral grading in the 10 ASPECTS locations for all vessels was substantial (weighted κ = 0.77; 95% CI: 0.74, 0.80). For the presence of postoperative collateral supplied by the ipsilateral external carotid artery in 10 ASPECTS locations (a total of 370 locations) using DSA as a reference test, the SS-ASL showed a sensitivity of 92% (183 of 199 locations; 95% CI: 87%, 95%) and a specificity of 83% (142 of 171 locations; 95% CI: 77%, 88%). The overall intermodality agreement of the changes in perfusion status was moderate (weighted κ = 0.59; 95% CI: 0.54, 0.65). Conclusion Superselective arterial spin labeling imaging precisely depicted the revascularization territory in patients with moyamoya disease who underwent bypass surgery, and it showed the changes in the vascular supplying territories before and after bypass surgery. © RSNA, 2020 See also the editorial by Hendrikse in this issue.
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http://dx.doi.org/10.1148/radiol.2020201448DOI Listing
December 2020