Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6–8 weeks old) mice.After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (KD =2.093(3) pM).Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. AffibodyIRDye800CW also exhibited high affinity for HER2 (KD =4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2–3 days before surgery to obtain high HER2-specific signal and contrast. Affibodybased NIR probes may require modifications to enhance mobilization to the tumor site.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Background: Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. Methods: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. Results: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. Conclusion This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen ; Acetates ; Acetic Acid ; Anti-Inflammatory Agents, Non-Steroidal ; Cicatrix ; Classification ; Cyclooxygenase 2 Inhibitors ; Diethylpropion ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Hospitals, University ; Incidence ; Korea ; Phenotype ; Propionates ; Prospective Studies ; Retrospective Studies ; Salicylates ; Salicylic Acid ; Stevens-Johnson Syndrome

PURPOSE: Day-care management of unruptured intracranial aneurysms can shorten hospital stay, reduce medical cost and improve outcome. We present the process, outcome and duration of hospital stay for the management of unruptured intracranial aneurysms via a neurointervention clinic in a single center during the past four years. MATERIALS AND METHODS: We analyzed 403 patients who were referred to Neurointervention Clinic at Asan Medical Center for aneurysm evaluation between January 1, 2011 and December 31, 2014. There were 141 (41%) diagnostic catheter angiographies, 202 (59%) neurointerventional procedures and 2 (0.6%) neurointerventional procedures followed by operation. We analyzed the process, outcome of angiography or neurointervention, and duration of hospital stay. RESULTS: There was no aneurysm in 58 patients who were reported as having an aneurysm in MRA or CTA (14 %). Among 345 patients with aneurysm, there were 283 patients with a single aneurysm (82%) and 62 patients with multiple aneurysms (n=62, 18%). Aneurysm coiling was performed in 202 patients (59%), surgical clipping in 14 patients (4%), coiling followed by clipping in 2 patients (0.6%) and no intervention was required in 127 patients (37%). The hospital stay for diagnostic angiography was less than 6 hours and the mean duration of hospital stay was 2.1 days for neurointervention. There were 4 procedure-related adverse events (2%) including 3 minor and 1 major ischemic strokes. CONCLUSION: Our study revealed that day-care management of unruptured intracranial aneurysms could be performed without an additional risk. It could enable rapid patient flow, shorten hospital stay and thus reduce hospital costs.
Aneurysm ; Angiography ; Catheters ; Chungcheongnam-do ; Hospital Costs ; Humans ; Intracranial Aneurysm* ; Length of Stay ; Outpatients* ; Stroke ; Surgical Instruments

PURPOSE: Hemodynamic factors are considered to play an important role in initiation and progression of the recurrence after endosaccular coiling of the intracranial aneurysms. We made paired virtual models of completely coiled aneurysms which were subsequently recanalized and compared to identify hemodynamic characteristics related to the recurred aneurysmal sac. MATERIALS AND METHODS: We created paired virtual models of computational fluid dynamics (CFD) in five aneurysms which were initially regarded as having achieved complete occlusion and then recurred during follow-up. Paired virtual models consisted of the CFD model of 3D rotational angiography obtained in the recurred aneurysm and the control model of the initial, parent artery after artificial removal of the coiled and recanalized aneurysm. Using the CFD analysis of the virtual model, we analyzed the hemodynamic characteristics on the neck of each aneurysm before and after its recurrence. RESULTS: High wall shear stress (WSS) was identified at the cross-sectionally identified aneurysm neck at which recurrence developed in all cases. A small vortex formation with relatively low velocity in front of the neck was also identified in four cases. The aneurysm recurrence locations corresponded to the location of high WSS and/or small vortex formation. CONCLUSION: Recanalized aneurysms revealed increased WSS and small vortex formation at the cross-sectional neck of the aneurysm. This observation may partially explain the hemodynamic causes of future recanalization after coil embolization.
Aneurysm* ; Angiography ; Arteries ; Embolization, Therapeutic ; Follow-Up Studies ; Hemodynamics* ; Humans ; Hydrodynamics* ; Intracranial Aneurysm ; Neck ; Parents ; Recurrence

Formation of de novo aneurysm from a junctional dilatation at the origin site of the posterior communicating artery (PcomA) has been rarely reported. In this case report, three females in sixth decades of age developed a de novo aneurysm from the junctional dilatation of the PComA with a tiny bleb-like lesion over 5 years after initial presentation.
Aneurysm* ; Arteries* ; Blister* ; Causality* ; Dilatation* ; Female ; Humans

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by air flow limitation, which is one of the leading causes of mortality worldwide. There have been many studies on survival rates in the world literature, but there have been few reports regarding the survival rate in Korean patients with COPD. Acute exacerbation is regarded as a risk factor for mortality in patients with COPD. The purpose of this study was to investigate the survival rate and the effect of acute exacerbations on the survival rate of Korean patients with COPD. METHODS: A total of 502 COPD patients who were diagnosed on the basis of history and lung function tests were enrolled in this study. The frequency of acute exacerbations, body mass index (BMI), C-reactive protein (CRP) and pulmonary hypertension were analyzed. RESULTS: The 3- and 5-year survival rates were 98% and 83%, respectively. The median survival time was 78 months. The median survival time was 55 months in 322 patients with one or more acute exacerbations. The 3- and 5-year survival rates were significantly lower in the 322 patients with one or more acute exacerbations than in those without any. The mortality rate was significantly higher in patients with CRP >3 mg/L than in those with CRP < or =3 mg/L (p<0.005); it was significantly higher in patients with pulmonary hypertension than in those without it (p<0.01). CONCLUSION: Because the 5-year survival rate is 83% in Korean patients with COPD, the management of stable patients with COPD should focus on the prevention of acute exacerbations.
Body Mass Index ; C-Reactive Protein ; Disease Progression ; Humans ; Hypertension, Pulmonary ; Lung Diseases ; Pulmonary Disease, Chronic Obstructive ; Respiratory Function Tests ; Risk Factors ; Survival Rate