Publications by authors named "Yun Jeong Lee"

97 Publications

Clinical Experience of Nusinersen in a Broad Spectrum of Spinal Muscular Atrophy: A Retrospective Study.

Ann Indian Acad Neurol 2020 Nov-Dec;23(6):796-801. Epub 2020 Oct 7.

Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

Background: Nusinersen has recently been approved and more widely used as first-line treatment of spinal muscular atrophy (SMA). This study aimed to evaluate the real-world experience of nusinersen use for patients with a broad spectrum of SMA.

Methods: We reviewed consecutive patients with SMA treated with nusinersen from April 2018 to April 2020. Data collected included clinical and diagnostic characteristics, molecular genetics, functional motor outcomes, and adverse events.

Results: Seven patients including four with SMA type 1 and three with SMA type 2 were treated with nusinersen. The median disease duration at the time of the first dose and the median follow-up duration were 37 months (range: 0.5-254 months) and 6.1 months (range: 2.1-22.1 months), respectively. Of the 41 lumbar punctures (LPs), seven fluoroscopy-guided LPs were successfully performed for two patients without sedation. All patients showed improvement in motor function even though the current tools for motor assessment seemed unable to detect subtle subjective improvement. All patients maintained a stable respiratory status. No patient has experienced a severe adverse event or discontinued treatment so far.

Conclusion: Although the number of patients in this study was small, our results suggest that nusinersen is effective even in patients with a later stage of the disease. Additional long-term prospective studies with more number of patients having a broad spectrum of diseases are needed to identify meaningful improvement in the motor function and quality of life after nusinersen treatment.
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http://dx.doi.org/10.4103/aian.AIAN_524_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900722PMC
October 2020

Long-Term Outcomes of Ophthalmic and Retinal Artery Occlusion After Cosmetic Facial Filler Injection.

Aesthet Surg J 2021 Feb 22. Epub 2021 Feb 22.

Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Background: Ophthalmic artery occlusion (OAO) and retinal artery occlusion (RAO) after facial filler injection have become increasingly significant due to the increment of cosmetic injection procedures for aesthetic purposes.

Objectives: To analyze the long-term visual outcomes and complications of cosmetic facial filler related OAO and RAO.

Methods: This single center, retrospective case series included 17 eyes of 16 filler related OAO or RAO patients with a follow-up period of one year or longer. Main outcome measures were best-corrected visual acuity (BCVA) and long-term complications.

Results: The mean age at diagnosis was 31.7 ± 9.7 years and all patients were female. The mean follow-up period was 5.4 ± 2.4 years. The mean BCVA was 2.34 and 2.41 logMAR at the initial and last visits, respectively, which indicates sustained long-term visual decrement. Ocular complications included retinal atrophy and degeneration (100.0%), optic atrophy and profound visual impairment (82.4%), strabismus (80.0%), retinal fibrous membrane (68.8%), posterior synechiae (35.3%), neovascularization (29.4%), iris atrophy and cataract (23.5%), corneal opacity and phthisis bulbi (17.6%), visual field defect and iris defect (11.8%), ophthalmoplegia (7.7%), and pupillary block (5.9%). Extra-ocular complications of brain infarction and depression were found in 25.0%, while skin necrosis was found in 13.3% of patients.

Conclusions: Facial filler related OAO or RAO resulted in long-term poor visual outcome, and most of the patients experienced irreversible visual impairment with no light perception despite various treatments. Various long-term ocular and extra-ocular complications were observed, which should be monitored for a long-term follow-up period. Our findings suggest that prevention should be stressed more than treatment.
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http://dx.doi.org/10.1093/asj/sjab099DOI Listing
February 2021

Nusinersen in spinal muscular atrophy type 1 from neonates to young adult: 1-year data from three Asia-Pacific regions.

J Neurol Neurosurg Psychiatry 2021 Feb 11. Epub 2021 Feb 11.

Departments of Pediatrics and Laboratory Medicine, and Translational Research Center of Neuromuscular Diseases, Kaohsiung University Medicine Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

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http://dx.doi.org/10.1136/jnnp-2020-324532DOI Listing
February 2021

The durability and effectiveness of sensor-augmented insulin pump therapy in pediatric and young adult patients with type 1 diabetes.

Ann Pediatr Endocrinol Metab 2020 Dec 31;25(4):248-255. Epub 2020 Dec 31.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Purpose: Despite the prevalent use of insulin pump therapy worldwide, few studies have been conducted among young patients with type 1 diabetes (T1D) in Korea. We investigated the durability and effectiveness of insulin pump therapy among Korean pediatric and young adult patients with T1D.

Methods: This study included 54 patients with T1D diagnosed at pediatric ages (range, 1.1-14.1 years) who initiated insulin pump therapy during 2016-2019 at Seoul National University Children's Hospital and Seoul National University Bundang Hospital. Clinical and biochemical data, including anthropometric measurements, insulin dose, and glycated hemoglobin (HbA1c) levels were obtained from T1D diagnosis to last follow-up.

Results: Forty-four patients (81.5%) continued insulin pump therapy with a median pump use duration of 2.9 years (range, 0.2-3.5 years); 10 discontinued the therapy within 12 months (<1 month, n=6; 1-6 months, n=1; and 6-12 months, n=3) due to physical interferences or financial problems. Older age (≥10 years of age) and longer diabetes duration (≥2 years) at the initiation of pump therapy were associated with discontinuation (P<0.05 for both). For patients continuing pump therapy, HbA1c levels significantly decreased after 1 year of therapy (from 8.9% to 8.1%, P<0.001) without changes in the body mass index z-scores or insulin dose. Although 4 patients experienced diabetic ketoacidosis, all recovered without complications.

Conclusion: Insulin pump therapy was effective in improving glycemic control in T1D patients during 12 months of treatment. Early initiation of insulin pump therapy after T1D diagnosis was helpful for continuing therapy.
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http://dx.doi.org/10.6065/apem.2040048.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788343PMC
December 2020

Dynamic changes in circulating PD-1CD8 T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer.

Eur J Cancer 2021 01 7;143:113-126. Epub 2020 Dec 7.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: The predictive value of immune monitoring with circulating CD8 T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1CD8 T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade.

Methods: Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8 T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1CD8 T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119).

Results: Circulating PD-1CD8 T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1 cells among CD8 T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8 T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8 T lymphocytes suppresses the effector functions of tumour antigen-specific CD8 T lymphocytes.

Conclusions: Dynamic changes in circulating PD-1CD8 T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors.
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http://dx.doi.org/10.1016/j.ejca.2020.10.028DOI Listing
January 2021

ABCB1 c.2677G>T/c.3435C>T diplotype increases the early-phase oral absorption of losartan.

Arch Pharm Res 2020 Nov 29;43(11):1187-1196. Epub 2020 Nov 29.

College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea.

Losartan has been shown to be a substrate of the drug-efflux transporter MDR1, encoded by the ABCB1 gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and function of P-glycoprotein (P-gp). We investigated the effects of ABCB1 diplotype on the pharmacokinetics of losartan. Thirty-eight healthy Korean volunteers with different ABCB1 diplotypes [c.2677G> T and c.3435C>T; carriers of GG/CC (n = 13), GT/CT (n = 12) and TT/TT (n = 13) diplotype] were recruited and administered a single 50 mg oral dose of losartan potassium. Losartan and its active metabolite E-3174 samples in plasma and urine were collected up to 10 and 8 h after drug administration, respectively, and the concentrations of both samples were determined by HPLC method. Significant differences were observed in C of losartan and losartan plus E-3174 (Lo + E) among the three diplotype groups (both P < 0.01). However, the power of the performed test is less than the desired power (0.800). The t of losartan and E-3174 in three diplotype groups were also significantly different (both P < 0.01). The AUC values of Lo + E were significantly different among the three diplotype groups until 6 h after losartan administration (P < 0.01). On the contrary, AUC at the periods of 8-10 h and 10 h-infinity of Lo + E were significantly lower in the TT/TT group than in the GG/CC group. Urinary excretion of losartan until 4 h after losartan administration in the TT/TT group was higher than that of the GG/CC group. These results suggest that c.2677G>T/c.3435C>T diplotypes of ABCB1 may significantly increase the early-phase absorption of losartan, but not the total absorption.
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http://dx.doi.org/10.1007/s12272-020-01294-3DOI Listing
November 2020

Effects of CYP2D6 genetic polymorphism on the pharmacokinetics of metoclopramide.

Arch Pharm Res 2020 Nov 27;43(11):1207-1213. Epub 2020 Nov 27.

College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea.

Metoclopramide inhibits the central and peripheral D receptors and is frequently prescribed in adults and children as an antiemetic or a prokinetic drug to control symptoms of upper gastrointestinal motor disorders. Metoclopramide is predominantly metabolized via N-dealkylation and it is primarily mediated by CYP2D6 which is highly polymorphic. Thus, the effects of CYP2D6 genetic polymorphism on the pharmacokinetics of metoclopramide were evaluated in this study. All volunteers were genotyped for CYP2D6 and divided into four different genotype groups (CYP2D6*wt/*wt [*wt = *1 or *2], CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10). Each subject received a single oral dose of metoclopramide 10 mg. Plasma concentrations of metoclopramide were measured by using HPLC-UV. Compared to CYP2D6*wt/*wt, AUC of CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 significantly increased by 1.5-, 2.3-, and 2.5-fold, respectively. C also increased significantly in comparison to CYP2D6*wt/*wt across all genotype groups, with 1.5-, 1.7-, and 1.7-fold increases seen in CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 groups, respectively. The CL/F of metoclopramide decreased in CYP2D6 genotype groups with decreased function alleles, as decreases of 37%, 56% and 61% were observed in CYP2D6*wt/10, *10/10, and *5/*10 genotype groups in comparison to the CYP2D6*wt/*wt group. In conclusion, the genetic polymorphisms of CYP2D6 significantly affected metoclopramide pharmacokinetics.
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http://dx.doi.org/10.1007/s12272-020-01293-4DOI Listing
November 2020

Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes.

Arch Pharm Res 2020 Dec 27;43(12):1356-1363. Epub 2020 Nov 27.

College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea.

The aim of this study was to investigate the  effects of paroxetine, a potent inhibitor of CYP2D6, on the pharmacokinetics of atomoxetine and its two metabolites, 4-hydroxyatomoxetine and N-desmethylatomoxetine, in different CYP2D6 genotypes. Twenty-six healthy subjects were recruited and divided into CYP2D6*wt/*wt (*wt=*1 or *2, n = 10), CYP2D6*wt/*10 (n = 9), and CYP2D6*10/*10 groups (n = 7). In atomoxetine phase, all subjects received a single oral dose of atomoxetine (20 mg). In paroxetine phase, after administration of a single oral dose of paroxetine (20 mg) for six consecutive days, all subjects received a single oral dose of atomoxetine with paroxetine. Plasma concentrations of atomoxetine and its metabolites were determined up to 24 h after dosing. During atomoxetine phase, there were significant differences in C and AUC of atomoxetine and N-desmethylatomoxetine among three genotype groups, whereas significant differences were not found in relation to CYP2D6*10 allele after administration of paroxetine. AUC ratios of 4-hydroxyatomoxetine and N-desmethylatomoxetine to atomoxetine were significantly different among three genotype groups during atomoxetine phase (all, P < 0.001), but after paroxetine treatment significant differences were not found. After paroxetine treatment, AUC of atomoxetine was increased by 2.3-, 1.7-, and 1.3-fold, in CYP2D6*wt/*wt, CYP2D6*wt/*10, and CYP2D6*10/*10 groups in comparison to atomoxetine phase, respectively. AUC ratio of 4-hydroxyatomoxetine to atomoxetine in each group was significantly decreased, whereas AUC ratio of N-desmethylatomoxetine to atomoxetine significantly increased after administration of paroxetine. In conclusion, paroxetine coadministration significantly affected pharmacokinetic parameters of atomoxetine and its two metabolites, 4-hydroxyatomoxetine and N-desmethylatomoxetine. When atomoxetine was administered alone, C, AUC and CL/F of atomoxetine were significantly different among the three CYP2D6 genotype groups. However, after paroxetine coadministration, no significant differences in these pharmacokinetic parameters were observed among the CYP2D6 genotype groups.
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http://dx.doi.org/10.1007/s12272-020-01300-8DOI Listing
December 2020

Relationship between plasma exposure of zolpidem and CYP2D6 genotype in healthy Korean subjects.

Arch Pharm Res 2020 Sep 13;43(9):976-981. Epub 2020 Jul 13.

College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea.

Zolpidem, a widely prescribed hypnotic agent, is extensively metabolized by cytochrome P450 (CYP) 3A4, and CYP2C9, CYP1A2 and CYP2D6 are also involved in the metabolism of zolpidem. The aim of the study was to investigate the effects of CYP2D6 genotypes on the exposure of zolpidem. The healthy male volunteers were divided into three different genotype groups (CYP2D6*wt/*wt [*wt = *1 or *2], CYP2D6*wt/*10, and CYP2D6*10/*10). Each subject received a single oral dose of zolpidem 5 mg with or without a steady-state concentration of clarithromycin (a potent inhibitor of CYP3A4), and plasma concentrations of zolpidem were measured up to 12 h after zolpidem dosing by using liquid chromatography-tandem mass spectrometry method. When zolpidem was administered alone, the exposure of zolpidem (the total areas under the curve and the mean peak plasma concentrations) was not significantly different among three different genotype groups. Even with the steady-state concentration of clarithromycin, a potent CYP3A4 inhibitor, there were no significant differences in the exposure of zolpidem in relation to CYP2D6 genotypes.
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http://dx.doi.org/10.1007/s12272-020-01250-1DOI Listing
September 2020

A Case of Consumptive Hypothyroidism in a 1-Month-Old Boy with Diffuse Infantile Hepatic Hemangiomas.

J Korean Med Sci 2020 Jun 8;35(22):e180. Epub 2020 Jun 8.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Consumptive hypothyroidism is a rare paraneoplastic syndrome characterized by excessive inactivation of the thyroid hormones due to increased type 3 iodothyronine deiodinase activity of tumors. We report the case of severe consumptive hypothyroidism in a 1-month-old boy with infantile hepatic hemangiomas who presented with cardiac failure and cholestasis. Diffuse infiltration of hepatic hemangiomas was detected on abdominal imaging studies, and thyroid function screening test revealed severe hypothyroidism, which necessitated the administration of higher-than-usual doses of levothyroxine for the normalization of thyroid function. The patient was successfully treated with propranolol, prednisolone, and levothyroxine, and he showed normal thyroid function at 3 months of age and normal neurodevelopment at 9 months of age. This case highlights the importance of early recognition and prompt management of consumptive hypothyroidism in patients with infantile hepatic hemangiomas.
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http://dx.doi.org/10.3346/jkms.2020.35.e180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279942PMC
June 2020

Outcomes of Adjunctive Drug-Coated Versus Uncoated Balloon after Atherectomy in Femoropopliteal Artery Disease.

Ann Vasc Surg 2020 Oct 25;68:391-399. Epub 2020 Apr 25.

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: The purpose of this study is to evaluate outcomes using drug-coated balloon (DCB) in comparison with uncoated balloon as adjunctive treatment after atherectomy for femoropopliteal artery lesions.

Methods: This single-center retrospective and prospective study included 115 patients with 126 femoropopliteal artery lesions treated with endovascular treatment using atherectomy. Of these, 58 patients received adjunctive DCB after atherectomy (group A) and 57 patients were managed with uncoated balloon after atherectomy (group B). Immediate and late clinical outcomes were compared.

Results: Baseline clinical and lesion data were comparable between the 2 groups. However, group A included more uses of rotational atherectomy (43.9% vs. 1.7%, P < 0.001) or embolization protection filter (53.0% vs. 6.7%, P = 0.001), and fewer cases requiring provisional stenting (4.5% vs. 18.3%, P = 0.014). Clinical primary patency at 1 year was significantly higher in group A than in group B (76.3% vs. 61.1%, P = 0.039). There was a trend toward higher 1-year target lesion revascularization (TLR)-free survival in group A (89.8% vs. 77.9% at 1 year, P = 0.275) without statistical significance. Proportional hazards regression analysis indicated that age (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.99, P = 0.016) and provisional stenting (HR 9.78, 95% CI 2.20-43.46, P = 0.003) were independent factors associated with restenosis after combined treatment with atherectomy and DCB.

Conclusions: In femoropopliteal artery disease, the combination of atherectomy with adjunctive DCB achieved better clinical outcomes in terms of clinical primary patency compared to atherectomy plus uncoated balloon while TLR-free survival may also be improved.
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http://dx.doi.org/10.1016/j.avsg.2020.04.032DOI Listing
October 2020

The Role of Nuclear Receptor Subfamily 1 Group H Member 4 (NR1H4) in Colon Cancer Cell Survival through the Regulation of c-Myc Stability.

Mol Cells 2020 May;43(5):459-468

Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Korea.

Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.
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http://dx.doi.org/10.14348/molcells.2020.0041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264475PMC
May 2020

Congenital Stationary Night Blindness due to Novel Gene Mutations in a Korean Patient.

Korean J Ophthalmol 2020 04;34(2):170-172

Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

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http://dx.doi.org/10.3341/kjo.2019.0080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105792PMC
April 2020

Clinical Features of Duane Retraction Syndrome: A New Classification.

Korean J Ophthalmol 2020 04;34(2):158-165

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

Purpose: We sought to provide a new classification system for Duane retraction syndrome (DRS) according to type and angle of strabismus during primary gaze and to analyze the clinical features of each DRS type.

Methods: The medical records of 65 DRS patients who visited the department of pediatric ophthalmology at Seoul National University Children's Hospital between 2010 and 2017 were retrospectively analyzed. Patients whose angle of exotropia at primary gaze exceeded 3 prism diopters (PDs) were classified as "Exo-Duane," those whose angle of strabismus at primary gaze did not exceed 3 PDs were classified as "Ortho-Duane," and those whose angle of esotropia at primary gaze exceeded 3 PDs were classified as "Eso-Duane."

Results: Among 65 DRS patients, Ortho-Duane was the most common (53.8%) type, followed by Eso-Duane (33.8%) and Exo-Duane (12.3%). The mean age at diagnosis was significantly higher in the Exo-Duane group than the Ortho-Duane or Eso-Duane group ( = 0.003 and < 0.001, respectively). A predominance of left eye involvement was observed in the Ortho-Duane (62.9%) and Eso-Duane (90.9%) groups. The frequencies of upshoot, downshoot, fissure narrowing, and globe retraction were not significantly different among the subgroups. Head-turn was more frequent in Eso-Duane patients than in Exo-Duane or Ortho-Duane patients ( = 0.001 and < 0.001, respectively). Myopia accounted for the most common refractive error among Exo-Duane patients (71.4%), while hyperopia was found more often in both Ortho-Duane (64.7%) and Eso-Duane (85.0%) patients. The majority of patients showed gross stereoacuity (93.1%), and a large proportion had good stereoacuity (Exo-Duane 60.0%, Ortho-Duane 81.3%, Eso-Duane 87.5%).

Conclusions: Our newly proposed classification of DRS according to type and angle of strabismus at primary gaze was practically useful and showed potential for use as an objective guideline in the clinical setting.
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http://dx.doi.org/10.3341/kjo.2019.0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105791PMC
April 2020

Advanced neuroimaging techniques for evaluating pediatric epilepsy.

Authors:
Yun Jeong Lee

Clin Exp Pediatr 2020 Mar 6;63(3):88-95. Epub 2020 Feb 6.

Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

Accurate localization of the seizure onset zone is important for better seizure outcomes and preventing deficits following epilepsy surgery. Recent advances in neuroimaging techniques have increased our understanding of the underlying etiology and improved our ability to noninvasively identify the seizure onset zone. Using epilepsy-specific magnetic resonance imaging (MRI) protocols, structural MRI allows better detection of the seizure onset zone, particularly when it is interpreted by experienced neuroradiologists. Ultra-high-field imaging and postprocessing analysis with automated machine learning algorithms can detect subtle structural abnormalities in MRI-negative patients. Tractography derived from diffusion tensor imaging can delineate white matter connections associated with epilepsy or eloquent function, thus, preventing deficits after epilepsy surgery. Arterial spin-labeling perfusion MRI, simultaneous electroencephalography (EEG)-functional MRI (fMRI), and magnetoencephalography (MEG) are noinvasive imaging modalities that can be used to localize the epileptogenic foci and assist in planning epilepsy surgery with positron emission tomography, ictal single-photon emission computed tomography, and intracranial EEG monitoring. MEG and fMRI can localize and lateralize the area of the cortex that is essential for language, motor, and memory function and identify its relationship with planned surgical resection sites to reduce the risk of neurological impairments. These advanced structural and functional imaging modalities can be combined with postprocessing methods to better understand the epileptic network and obtain valuable clinical information for predicting long-term outcomes in pediatric epilepsy.
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http://dx.doi.org/10.3345/kjp.2019.00871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073377PMC
March 2020

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study.

J Clin Neurol 2020 Jan;16(1):53-59

Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

Background And Purpose: The US Food and Drug Administration approval for perampanel has only recently been expanded to patients as young as 4 years, and so there have been few real-life studies of the effects of perampanel in pediatric patients. The aim of this study was to determine the long-term efficacy, factors affecting treatment response, and tolerability of perampanel as an add-on therapy in pediatric patients aged 4 years or older with epilepsy.

Methods: This multicenter retrospective observational study collected data from pediatric epilepsy centers of four Korean national universities. Changes in the seizure frequency from baseline, adverse events, and retention rates were obtained at 3, 6, and 12 months. Adverse events and discontinuation profiles were obtained to assess tolerability.

Results: This study included 220 children and adolescents (117 males and 103 females) aged 4 to 20 years. The overall response rate was 43.6%, and the seizure-freedom rate was 17.7%. Factors affecting a good treatment response were the absence of intellectual disability, small number of concomitant antiepileptic drugs, and low baseline seizure frequency. Eighty-eight patients (40%) experienced adverse events, but they mostly were of mild severity and resolved after the dose reduction or discontinuation of perampanel. The retention rates at 3, 6, and 12 months were 85.0%, 71.8%, and 50.5%, respectively.

Conclusions: Adjunctive treatment with perampanel was efficacious and tolerated in pediatric patients aged 4 years or older with epilepsy. Early perampanel treatment may help to reduce the burden of their seizures and improve their quality of life.
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http://dx.doi.org/10.3988/jcn.2020.16.1.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974830PMC
January 2020

Effects of steady-state clarithromycin on the pharmacokinetics of zolpidem in healthy subjects.

Arch Pharm Res 2019 Dec 9;42(12):1101-1106. Epub 2019 Dec 9.

School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

Zolpidem is extensively metabolized by CYP3A4, CYP2C9 and CYP1A2. Previous studies demonstrated that pharmacokinetics of zolpidem was affected by CYP inhibitors, but not by short-term treatment of clarithromycin. The objective of this study was to investigate the effects of steady-state clarithromycin on the pharmacokinetics of zolpidem in healthy subjects. In the control phase, 33 subjects received a single dose of zolpidem (5 mg). One week later, in the clarithromycin phase, the subjects received clarithromycin (500 mg) twice daily for 5 days to reach steady state concentrations, followed by zolpidem (5 mg) and clarithromycin (500 mg). In each phase, plasma concentrations of zolpidem were evaluated up to 12 h after drug administration by using liquid chromatography-tandem mass spectrometry method. In the clarithromycin phase, mean total area under the curve of zolpidem (AUC) was 1.62-fold higher and the time to reach peak plasma concentration of zolpidem (t) was prolonged by 1.95-fold compared to the control phase. In addition, elimination half-life (t) of zolpidem was 1.40-fold longer during co-administration with clarithromycin and its apparent oral clearance (CL/F) was 36.2% lower with clarithromycin administration. The experimental data demonstrate the significant pharmacokinetic interaction between zolpidem and clarithromycin at steady-state.
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http://dx.doi.org/10.1007/s12272-019-01201-5DOI Listing
December 2019

Conjunctival pigmented lesion: Clinicopathological analysis of 85 cases in Korean population.

Sci Rep 2019 12 3;9(1):18204. Epub 2019 Dec 3.

Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

To evaluate histopathological characteristics of conjunctival pigmented lesions and analyze clinical features related to histologic classification in Asian population, we analyzed medical records, anterior segment photographs, and histological specimen of 85 eyes who had undergone biopsy for pigmented conjunctival lesions at Seoul National University Hospital between 1999 and 2018. Compound nevus was the most common type of conjunctival pigmented lesions (67.1%), followed by conjunctival melanocytic intraepithelial neoplasia (primary acquired melanosis)(11.8%), subepithelial nevus (8.2%), and malignant melanoma (MM)(7.1%). Patients with compound nevus were younger than those with non-compound nevus (22.1 ± 17.0 vs 39.9 ± 18.8 years, p < 0.001), while patients with MM were older than those without melanoma (55.7 ± 18.2 vs 25.8 ± 18.0 years, p = 0.001). The lesion in compound nevus tended to be more frequently located on the temporal conjunctiva than that in the non-compound nevus group (54.4% vs 32.1%, p = 0.053), and feeder vessels were associated with most of compound nevus (98.2% vs 78.6% of non-compound nevus, p = 0.005). The lesion in MM was larger, involved multiple quadrants, and had extrabulbar location than lesions without melanoma (p < 0.001, p < 0.001, and p = 0.002, respectively). Together, the results would help clinicians to distinguish benign conjunctival pigmentations from malignant counterparts in clinical practice without biopsy.
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http://dx.doi.org/10.1038/s41598-019-54786-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890774PMC
December 2019

High-Sensitivity C-Reactive Protein Is Associated with Prediabetes and Adiposity in Korean Youth.

Metab Syndr Relat Disord 2020 02 26;18(1):47-55. Epub 2019 Nov 26.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Obesity, a chronic low-grade inflammatory state, increases the risk of cardiovascular disease. Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with cardiovascular disease, type 2 diabetes, and metabolic syndrome in adults. This study aimed to determine the association of hs-CRP and cardiometabolic risk factors, including obesity, prediabetes, hypertension, and dyslipidemia, in the nationally representative data of Korean youth. Anthropometric, biochemical, physical activity (PA), and nutritional survey data were collected for 1,723 youths (918 boys, 53.5%), aged 10-18 years, from the Korea National Health and Nutrition Examination Survey (2015-2017). Participants were classified into three groups according to hs-CRP tertile. Abdominal obesity, impaired fasting glucose, elevated triglyceride, decreased high-density lipoprotein (HDL) cholesterol and elevated blood pressure, and prediabetes [glycated hemoglobin (HbA1c) 5.7%-6.4%] were compared according to sex and hs-CRP tertile. The ranges of each hs-CRP tertile were ≤0.3, 0.31-0.5, and >0.5 mg/L, respectively. hs-CRP was positively associated with body mass index (BMI) z-score ( < 0.001) and HbA1c ( = 0.012), and negatively with HDL cholesterol ( = 0.029), after adjusting confounding variables, including age, sex, BMI, white blood cell count, PA, and nutritional factors. The upper tertile of hs-CRP was associated with obesity [adjusted odds ratio (aOR) 12.07,  < 0.001] and prediabetes (aOR 3.08,  = 0.002). Elevated hs-CRP is associated with high BMI z-score and HbA1c, and low HDL cholesterol in Korean children and adolescents. Hence, hs-CRP could be a reliable indicator for adiposity, prediabetes, and abnormal lipid metabolism in the pediatric population.
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http://dx.doi.org/10.1089/met.2019.0076DOI Listing
February 2020

The association between progression of coronary artery calcium and colorectal adenoma: A retrospective follow-up study of asymptomatic Koreans.

Medicine (Baltimore) 2019 Oct;98(42):e17629

Division of Cardiology, Gangnam Severance Hospital Cardiovascular Center, Yonsei University Health System.

The potential relationship between coronary artery calcium (CAC) and colorectal adenoma has been widely indicated. This study aimed to investigate the relationship between the risk of colorectal adenoma and CAC progression in asymptomatic Korean adults who underwent serial assessments by colonoscopy and CAC scan.A total of 754 asymptomatic participants, who had undergone serial CAC scans and colonoscopies for screening, were enrolled. Changes in CAC were assessed according to the absolute change between baseline and follow-up results. CAC progression was defined using Multi-Ethnic Study of Atherosclerosis method. Risk for adenoma at follow-up colonoscopy was determined using hazard ratio (HR) by Cox regression. The area under the receiver operating characteristic (ROC) curve was measured.The mean follow-up duration was 3.4 ± 2.5 years. CAC progression was found in 215 participants (28.5%). Participants with adenoma at index colonoscopy showed a higher rate of CAC progression than those without (38.8% vs 23.6%, P < .01). In participants with adenoma at index colonoscopy, CAC progression significantly increased the cumulative risk for adenoma at follow-up colonoscopy (HR = 1.48, 95% confidence interval [CI] 1.06-2.06, log-rank P = .021). In multivariate analysis, male sex (HR = 2.57, 95% CI 1.22-5.42, P = .013), ≥3 adenomas at index colonoscopy (HR = 2.60, 95% CI 1.16-5.85, P = .021), and CAC progression (HR = 2.74, 95% CI 1.48-5.08, P = .001) increased the risk of adenoma at follow-up colonoscopy. In participants without adenoma at index colonoscopy, neither baseline CAC presence nor CAC progression increased the risk of adenoma at follow-up colonoscopy. The interaction between CAC progression and adenoma at index colonoscopy was significant in multivariable model (P = .005). In the ROC analysis, AUC of CAC progression for adenoma at follow-up colonoscopy was 0.625 (95% CI 0.567-0.684, P < .001) in participants with adenoma at index colonoscopy.Participants with CAC progression, who are at high risk of coronary atherosclerosis, may need to be considered for follow-up evaluation of colorectal adenoma, especially those with adenoma at index colonoscopy.
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http://dx.doi.org/10.1097/MD.0000000000017629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824637PMC
October 2019

How can the occurrence of delayed elevation of thyroid stimulating hormone in preterm infants born between 35 and 36 weeks gestation be predicted?

PLoS One 2019 23;14(8):e0220240. Epub 2019 Aug 23.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objective: We evaluated frequency and risk factors of delayed TSH elevation (dTSH) and investigated follow-up outcomes in the dTSH group with venous TSH (v-TSH) levels of 6-20 mU/L according to whether late preterm infants born at gestational age (GA) 35-36 weeks had risk factors.

Methods: The medical records of 810 neonates (414 boys) born at Seoul National University Hospital who had a normal neonatal screening test (NST) and underwent the first repeat venous blood test at 10-21 days post birth were reviewed.

Results: Seventy-three (9.0%) neonates showed dTSH, defined as a v-TSH level ≥6.0 mU/L, 12 of whom (1.5%) were started on levothyroxine medication. A multivariate-adjusted model indicated that a low birth weight (LBW <2,000 g), a congenital anomaly, and exposure to iodine contrast media (ICM) were significant predictors for dTSH (all p < 0.05). Among these 73 dTSH infants, all 5 infants with TSH levels ≥20 mU/L began levothyroxine medication, and 6 of 16 infants with v-TSH levels of 10-20 mU/L were indicated for levothyroxine, regardless of coexisting risk factors. However, only 1 of 52 infants with v-TSH levels of 6-10 mU/L who had a congenital anomaly was indicated for levothyroxine. All healthy late preterm infants, including LBW and multiple births, with v-TSH levels of 6-10 mU/L exhibited normal thyroid function.

Conclusions: dTSH was detected in 9.0% and levothyroxine was indicated in 1.5% of infants born at GA 35-36 weeks, particularly those with a LBW, a congenital anomaly, or history of ICM exposure. Either levothyroxine or retesting is indicated for late preterm neonates with TSH levels ≥10 mU/L regardless of risk factors. If healthy preterm neonates show v-TSH levels of 6-10 mU/L, a second repeat test may not be necessary; however, further studies are required to set a threshold for retesting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220240PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707626PMC
February 2020

Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors.

Int J Clin Oncol 2019 Dec 27;24(12):1515-1525. Epub 2019 Jul 27.

Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors.

Methods: We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens.

Results: Eleven patients aged < 3 years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5 cm), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1 months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3 years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively.

Conclusions: Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.
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http://dx.doi.org/10.1007/s10147-019-01517-8DOI Listing
December 2019

Extremely Early Onset Transthyretin Familial Amyloid Polyneuropathy with a Leu55Pro Mutation: A Pediatric Case Report and Literature Review.

Neuropediatrics 2019 10 18;50(5):322-326. Epub 2019 Jul 18.

Department of Pediatrics, School of Medicine, Kyungpook National University Hospital, Daegu, South Korea.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant disease caused by the deposition of amyloid fibrils composed of TTR proteins. Symptoms of this disease include progressive sensorimotor neuropathy, cardiomyopathy, and involvement of other organs. We described a pediatric case of extremely early onset TTR-FAP with a Leu55Pro mutation. A 17-year-old boy began to suffer from lower limb weakness, gait disturbance, and decreased sensation from 14 years of age onward. He presented with hypertrophic cardiomyopathy, periorbital and scleral ecchymosis, anhidrosis, orthostatic intolerance, and gastrointestinal autonomic dysfunction including nausea, vomiting, and diarrhea alternating with constipation. The patient's older sister had developed similar gastrointestinal symptoms from 20 years of age onward and was diagnosed as having hypertrophic cardiomyopathy. The boy's biopsy results showed infiltrated amyloid deposition on subcutaneous fat tissue and endocardium. Genetic analysis of the gene demonstrated that both the patient and his sister had a pathogenic mutation, c.224T > C (Leu55Pro). Both patients were prescribed tafamidis, a TTR stabilizing agent. Although a majority of TTR-FAPs occur during adulthood, it should be suspected, even in pediatric populations, when symmetric length dependent neuropathy occurs in conjunction with a family history of neuropathy, autonomic neuropathy, and/or cardiomyopathy.
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http://dx.doi.org/10.1055/s-0039-1693145DOI Listing
October 2019

Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials.

J Clin Pharm Ther 2019 Oct 9;44(5):685-692. Epub 2019 Jul 9.

School of Pharmacy, Sungkyunkwan University, Suwon, Korea.

What Is Known And Objective: Angioedema (AE) caused by angiotensin-converting enzyme inhibitors (ACEIs) requires prompt and appropriate management, but current treatment options are limited to symptomatic treatment. Icatibant is a bradykinin receptor antagonist approved for hereditary AE treatment. Some recent studies showed a potential role for icatibant on ACEI-induced AE while others have shown no promising effect. This meta-analysis of randomized controlled trials (RCTs) was conducted to provide evidence for the use of icatibant in the treatment of ACEI-induced AE.

Methods: Relevant RCTs that examined the effects of icatibant for ACEI-induced AE were retrieved from EMBASE, PubMed and Cochrane Library (Central). Included articles for the meta-analysis were assessed using the Cochrane risk of bias tool. For meta-analysis, the pooled mean differences (MD) with 95% CIs and the pooled relative risk (RR) with 95% CIs were calculated using RevMan 5.3. The systematic review was performed in accordance with the PRISMA statement.

Results And Discussion: A total of 234 records were identified after searching the databases. In total, three RCTs involving 179 patients were included in the meta-analysis. The three RCTs had a low risk of bias and the characteristics of the participants and the outcome measures were similar among the RCTs. Treatment with icatibant shortened the time to achieve complete resolution of ACEI-induced AE symptoms compared to placebo or conventional treatments. However, the difference was not statistically significant (MD: -7.77 hours; 95% CI: -25.18-9.63 hours). There were no differences between groups in terms of drug-related adverse effects, apart from the reactions at the site of injection (RR: 1.35; 95% CI: 0.53-3.45).

What Is New And Conclusion: This meta-analysis evaluated the effectiveness and tolerability of icatibant therapy for ACEI-induced AE, but the benefit of icatibant therapy over placebo or conventional treatment strategies could not be shown.
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http://dx.doi.org/10.1111/jcpt.12997DOI Listing
October 2019

Early-life exposure to endocrine-disrupting chemicals and pubertal development in girls.

Ann Pediatr Endocrinol Metab 2019 Jun 30;24(2):78-91. Epub 2019 Jun 30.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Over the last decades, the onset of puberty in girls has occurred earlier, but the tempo of pubertal progression has been relatively slower, resulting in a younger age at puberty onset without a change in age at menarche. Sufficient energy availability and adiposity contribute to early pubertal development, and environmental factors, such as endocrine-disrupting chemicals (EDCs), may affect not only the control of energy balance, but also puberty and reproduction. EDCs are hormonally active substances that can perturb puberty by acting both peripherally on target organs, such as adipose tissue or adrenal glands, and/or centrally on the hypothalamic-pituitary-gonadal (HPG) axis. Depending on whether the exposure takes place earlier during fetal and neonatal life or later during early childhood, EDCs can lead to different outcomes through different mechanisms. Evidence of associations between exposures to EDCs and altered pubertal timing makes it reasonable to support their relationship. However, human epidemiologic data are limited or inconsistent and cannot provide sufficient evidence for a causal relationship between EDC exposure and changes in pubertal timing. Further investigation is warranted to determine the overall or different effects of EDCs exposure during prenatal or childhood windows on pubertal milestones and to reveal the underlying mechanisms, including epigenetic marks, whereby early-life exposure to EDCs affect the HPG-peripheral tissue axis.
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http://dx.doi.org/10.6065/apem.2019.24.2.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603611PMC
June 2019

Central nervous system vasculitis from Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children: A case report.

Brain Dev 2019 Oct 14;41(9):820-825. Epub 2019 Jun 14.

Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea. Electronic address:

Background: Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders (EBV-T/NK-LPD) is a group of rare disorders resulting from EBV-infected T/NK-cells. It manifests as a broad spectrum of clinical symptoms according to immunologic status and viral load of an infected patient. Here, we report a boy who developed central nervous system (CNS) vasculitis and myelopathy as possible neurologic manifestations of EBV-T/NK-LPD.

Case Report: A 16-year-old boy came to our hospital with a necrotic skin lesion on his right shoulder. He suffered from local skin reactions with high fevers after mosquito bites since he was 10 years old. During the evaluation of his skin lesion, he suddenly developed left facial palsy. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) showed acute infarctions of the pons and middle cerebellar peduncle and irregularities of both anterior inferior cerebellar arteries. Serologic testing showed an elevation of total Ig E levels, anti-VCA IgG levels, and anti-EA IgG titers. EBV DNA copy numbers of the whole blood and cerebrospinal fluid (CSF) were elevated. Biopsy of the right shoulder skin showed extranodal NK/T-cell lymphoma. According to clinical features and laboratory findings, he was diagnosed with EBV-T/NK-LPD. He was treated with chemotherapy and hematopoietic stem cell transplantation but developed recurrent infarctions during treatment.

Conclusion: This case showed the diagnostic challenge of neurologic manifestations of EBV-T/NK-LPD. EBV-T/NK-LPD-associated CNS vasculitis needs to be considered as a differential diagnosis of CNS vasculitis, when it is accompanied by the typical clinical spectrum of EBV-T/NK-LPD such as severe mosquito bite allergy, extranodal NK/T-cell lymphoma.
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http://dx.doi.org/10.1016/j.braindev.2019.05.009DOI Listing
October 2019

Acute Necrotizing Encephalopathy in Children: a Long Way to Go.

J Korean Med Sci 2019 May 20;34(19):e143. Epub 2019 May 20.

Department of Pediatrics, School of Medicine, Kyungpook National University and Kyungpook National University Children's Hospital, Daegu, Korea.

Background: Acute necrotizing encephalopathy (ANE) is a rare, but potentially life threatening neurological condition in children. This study aimed to investigate its clinical spectrum, diagnostic and therapeutic dilemma, and prognosis.

Methods: Twelve children with ANE were included in the study. The diagnosis was made by clinical and radiological characteristics from January 1999 to December 2017 and their clinical data were retrospectively analyzed.

Results: A total of 12 children aged 6 to 93 months at onset (5 male: 7 female) were evaluated. The etiology was found in 4 of them (influenza A, H1N1; coxsackie A 16; herpes simplex virus; and gene/mycoplasma). The most common initial presentations were seizures (67%) and altered mental status (58%). The majority of the subjects showed elevation of aspartate aminotransferase/alanine aminotransferase with normal ammonia and increased cerebrospinal fluid protein without pleocytosis. Magnetic resonance imaging revealed increased T2 signal density in bilateral thalami in all patients, but the majority of the subjects (67%) also had lesions in other areas including tegmentum and white matter. Despite the aggressive immunomodulatory treatments, the long-term outcome was variable. One child and two sisters with genetic predisposition passed away.

Conclusion: ANE is a distinctive type of acute encephalopathy with diverse clinical spectrum. Even though the diagnostic criteria are available, they might not be watertight. In addition, treatment options are still limited. Further studies for better outcome are needed.
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http://dx.doi.org/10.3346/jkms.2019.34.e143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522889PMC
May 2019

Relationship between systolic hypertension assessed by 24-hour ambulatory blood pressure monitoring and aortic diameters in young women with Turner syndrome.

Clin Endocrinol (Oxf) 2019 07 30;91(1):156-162. Epub 2019 Apr 30.

Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

Objective: Patients with Turner syndrome (TS) are at high risk for cardiovascular morbidity and mortality due to aortic dilation. We evaluated the prevalence of hypertension and its risk factors and investigated the relationship between systolic hypertension and aortic diameter in young patients with TS.

Design: Observational, cross-sectional study.

Patients And Measurements: Forty-two patients with TS (15-35 years) who had achieved final adult heights underwent 24-h ambulatory blood pressure monitoring (ABPM). Fasting glucose, insulin and lipid profiles were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Echocardiography was performed to evaluate aortic diameters (aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction and ascending aorta), which were converted into Turner-specific z-scores.

Results: Systolic and/or diastolic hypertension was identified in 71.4% (n = 30) of patients, as assessed by 24-hour ABPM. Twenty-eight patients (66.7%) were nondippers. Patients with systolic hypertension (n = 8, 19.0%) had a higher weight, waist circumference and HOMA-IR levels than those without hypertension (P < 0.05 for all). After adjusting for covariates, HOMA-IR was independently associated with systolic hypertension (odds ratio 10.1, P = 0.043). After adjusting for age and bicuspid aortic valve, systolic hypertension was independently related to increased aortic diameter at the aortic annulus (β = 1.064, P = 0.009) and sinotubular junction (β = 1.124, P = 0.016).

Conclusions: Hypertension is highly prevalent and independently associated with IR in young patients with TS. The significant relationship between systolic hypertension and aortic diameters underscores the importance of BP and IR control.
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http://dx.doi.org/10.1111/cen.13995DOI Listing
July 2019

A family with a mild form of congenital nystagmus and optic disc coloboma caused by a novel PAX6 mutation.

Gene 2019 Jul 12;705:177-180. Epub 2019 Apr 12.

Department of Neurology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea. Electronic address:

Congenital nystagmus (CN) is a heterogeneous disease that shows variable clinical features. There are a few mutations that are known to cause CN. Among them, a PAX6 mutation is known to cause CN with an extremely high frequency of aniridia. Here, we report on a family with an autosomal dominant PAX6 mutation, c.214G > A (p.Gly72Ser.), who presented with CN in the absence of aniridia. This study describes detailed clinical findings, including videonystagmography and fundus photography findings and emphasizes the importance of screening for the PAX6 gene in patients who present with CN in the absence of aniridia, as this will further elucidate the known phenotypes of PAX6-related diseases.
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http://dx.doi.org/10.1016/j.gene.2019.04.035DOI Listing
July 2019