Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Background: and Purpose: Language dysfunction is a symptom common to patients with Alzheimer's disease (AD). Speech feature analysis may be a patient-friendly screening test for early-stage AD. We aimed to investigate the speech features of amnestic mild cognitive impairment (aMCI) compared to normal controls (NCs). Methods: Spoken responses to test questions were recorded with a microphone placed 15 cm in front of each participant. Speech samples delivered in response to four spoken test prompts (free speech test, Mini-Mental State Examination [MMSE], picture description test, and sentence repetition test) were obtained from 98 patients with aMCI and 139 NCs.Each recording was transcribed, with speech features noted. The frequency of the ten speech features assessed was evaluated to compare speech abilities between the test groups. Results: Among the ten speech features, the frequency of pauses (p=0.001) and mumbles (p=0.001) were significantly higher in patients with aMCI than in NCs. Moreover, MMSE score was found to negatively correlate with the frequency of pauses (r=−0.441, p<0.001) and mumbles (r=−0.341, p<0.001). Conclusions Frequent pauses and mumbles reflect cognitive decline in aMCI patients in episodic and semantic memory tests. Speech feature analysis may prove to be a speech-based biomarker for screening early-stage cognitive impairment.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

PURPOSE: A hybrid-dynamic conformal arc therapy (HDCAT) technique consisting of a single half-rotated dynamic conformal arc beam and static field-in-field beams in two directions was designed and evaluated in terms of dosimetric benefits for radiotherapy of lung cancer. MATERIALS AND METHODS: This planning study was performed in 20 lung cancer cases treated with the VERO system (BrainLAB AG, Feldkirchen, Germany). Dosimetric parameters of HDCAT plans were compared with those of three-dimensional conformal radiotherapy (3D-CRT) plans in terms of target volume coverage, dose conformity, and sparing of organs at risk. RESULTS: HDCAT showed better dose conformity compared with 3D-CRT (conformity index: 0.74 ± 0.06 vs. 0.62 ± 0.06, p < 0.001). HDCAT significantly reduced the lung volume receiving more than 20 Gy (V20: 21.4% ± 8.2% vs. 24.5% ± 8.8%, p < 0.001; V30: 14.2% ± 6.1% vs. 15.1% ± 6.4%, p = 0.02; V40: 8.8% ± 3.9% vs. 10.3% ± 4.5%, p < 0.001; and V50: 5.7% ± 2.7% vs. 7.1% ± 3.2%, p < 0.001), V40 and V50 of the heart (V40: 5.2 ± 3.9 Gy vs. 7.6 ± 5.5 Gy, p < 0.001; V50: 1.8 ± 1.6 Gy vs. 3.1 ± 2.8 Gy, p = 0.001), and the maximum spinal cord dose (34.8 ± 9.4 Gy vs. 42.5 ± 7.8 Gy, p < 0.001) compared with 3D-CRT. CONCLUSIONS: HDCAT could achieve highly conformal target coverage and reduce the doses to critical organs such as the lung, heart, and spinal cord compared to 3D-CRT for the treatment of lung cancer patients.
Heart ; Humans ; Lung Neoplasms ; Lung ; Organs at Risk ; Radiotherapy ; Radiotherapy, Conformal ; Spinal Cord

PURPOSE: The present study investigated the diagnostic accuracy and clinical implications of moderate stenosis (50–69%, Coronary Artery Disease Reporting and Data System, grade 3) on coronary computed tomography angiography (CCTA), compared with invasive coronary angiography (ICA). MATERIALS AND METHODS: Two hundred and seventy-six patients who underwent ICA due to moderate stenosis alone on CCTA were selected from our prospective registry cohort. RESULTS: Diagnostic concordance between CCTA and ICA was found in only 50 (18%) patients. Among the 396 vessels and 508 segments with moderate stenosis, diagnostic concordance was found in 132 vessels (33%) and 127 segments (25%). Segments with calcified plaque had lower diagnostic concordance than those with mixed or non-calcified plaque (22% vs. 28% vs. 27%, respectively, p=0.001). While calcified plaque burden did not have an influence on severe stenosis (≥70%) on ICA, higher burden of non-calcified plaque was correlated with a greater incidence of ICA-based severe stenosis, which was more frequent in patients with ≥3 segments of non-calcified plaque (75%) than those without non-calcified plaque (22%, p < 0.001). Typical angina and mixed or non-calcified plaque were correlated with a higher incidence of under-diagnosis, while the use of next-generation computed tomography scanners reduced the incidence of under-diagnosis. Increased body weight, left circumflex artery involvement, and calcified plaque were independent factors that increased the risk of over-diagnosis of CCTA. CONCLUSION: The diagnosis of moderate stenosis by CCTA may be limited in estimating the exact degree of ICA-based anatomical stenosis. Unlike calcific burden, non-calcific burden was positively correlated with the presence of severe stenosis on ICA.
Angina, Stable* ; Angiography* ; Arteries ; Body Weight ; Cohort Studies ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis* ; Diagnosis ; Humans ; Incidence ; Information Systems ; Prospective Studies

Deer serve as reservoirs of tick-borne pathogens that impact on medical and veterinary health worldwide. In the Republic of Korea, the population of Korean water deer (KWD, Hydropotes inermis argyropus) has greatly increased from 1982 to 2011, in part, as a result of reforestation programs established following the Korean War when much of the land was barren of trees. Eighty seven Haemaphysalis flava, 228 Haemaphysalis longicornis, 8 Ixodes nipponensis, and 40 Ixodes persulcatus (21 larvae, 114 nymphs, and 228 adults) were collected from 27 out of 70 KWD. A total of 89/363 ticks (266 pools, 24.5% minimum infection rate) and 5 (1.4%) fed ticks were positive for Anaplasma phagocytophilum using nested PCR targeting the 16S rRNA and groEL genes, respectively. The 16S rRNA gene fragment sequences of 88/89 (98.9%) of positive samples for A. phagocytophilum corresponded to previously described gene sequences from KWD spleen tissues. The 16S rRNA gene fragment sequences of 20/363 (5.5%) of the ticks were positive for A. bovis and were identical to previously reported sequences. Using the ITS specific nested PCR, 11/363 (3.0%) of the ticks were positive for Bartonella spp. This is the first report of Anaplasma and Bartonella spp. detected in ticks collected from KWD, suggesting that ticks are vectors of Anaplasma and Bartonella spp. between reservoir hosts in natural surroundings.
Anaplasma/genetics/*physiology ; Animals ; Arachnid Vectors/microbiology ; Bartonella/genetics/*physiology ; Chaperonin 60/genetics ; Deer/parasitology ; Disease Reservoirs/veterinary ; RNA, Ribosomal, 16S/genetics ; Republic of Korea/epidemiology ; Ticks/*microbiology

Insulin-induced allergy is a rare adverse drug reaction since the introduction of recombinant human insulin. However, recombinant insulin-induced allergy is still being reported in 0.1% to 2% of all patients treated with insulin. This allergic reaction varies from mild localized skin reactions to life-threatening anaphylaxis. It has been shown that one-third of insulin allergy cases is related to insulin itself and the remaining occur due to preservatives contained in the insulin preparations, such as protamine, zinc, or metacresol. This case report describes a 75-year-old woman with poorly controlled diabetes who experienced insulin allergy. She complained of urticaria with itching after the injection of insulin. Allergic skin tests showed positive responses to all available human insulin preparations, and specific IgE to human insulin was also detected, which suggested that her urticaria was developed by insulin itself. This is the first case of insulin allergy that was sensitive to all available human insulin preparations and confirmed by the presence of specific IgE to human insulin. It is important to remember that allergic reactions to insulin may be directly associated with adherence and can be the reason of poor glucose control.
Aged ; Anaphylaxis ; Drug-Related Side Effects and Adverse Reactions ; Female ; Glucose ; Humans* ; Hypersensitivity* ; Immunoglobulin E ; Insulin Antibodies ; Insulin* ; Pruritus ; Skin ; Skin Tests ; Urticaria ; Zinc

We aimed to estimate the cutoff value of glycated hemoglobin (HbA1c, A1c) for fasting plasma glucose (FPG) of 126 mg/dL in the Korean adult population, using the 2011 Korea National Health and Nutrition Examination Survey. A total of 5,421 participants without a history of diabetes and over 19 years of age were included in the analysis. A point-wise area under the receiver operating characteristic curve was used to estimate the optimal A1c cutoff value. A1c threshold of 6.1% produced the highest sum of sensitivity (85.2%) and specificity (90.5%) for FPG of 126 mg/dL (area under the curve, 0.941, P<0.001). A1c of 6.5% produced a sensitivity of 67.7% and specificity of 98.0% for FPG of 126 mg/dL. Considering A1c as one of three criteria for the diagnosis of diabetes and the specificity of an A1c cutoff of 6.5%, the current diagnostic criteria of A1c> or =6.5% might be acceptable in the Korean adult population.
Adult ; Blood Glucose* ; Diabetes Mellitus ; Diagnosis ; Fasting* ; Hemoglobin A, Glycosylated* ; Humans ; Korea ; Nutrition Surveys* ; ROC Curve ; Sensitivity and Specificity

The purpose of this study was to examine the urban-rural differences in the prevalence and associated factors with type 2 diabetes mellitus (T2DM) in Korean adults. A total of 1,060 adults >30 yr of age from urban (189 males and 331 females) and rural districts (219 males and 321 females) were recruited. Anthropometric measures, blood pressure, lipid profiles, and fasting and 2-hr after 75-g oral glucose load blood glucose were obtained. The crude- and age-standardized prevalence of T2DM was 15.4% and 14.5%, and 11.7% and 8.6% in urban and rural districts, respectively. Diabetic subjects were older and obese, and had a higher triglyceride level, and systolic blood pressure compared to non-diabetes in both population. Multivariate regression analysis revealed that older age, high triglyceride levels, central obesity, and hypertension were significantly associated with T2DM in both areas. Low monthly incomes were significantly associated with T2DM in urban population, while a family history of T2DM was significantly associated with T2DM in rural area. T2DM is more prevalent in urban than in rural population, and low economic status or genetic factor is differently associated with T2DM in both population, respectively.
Adult ; Age Factors ; Aged ; Diabetes Mellitus, Type 2/complications/*epidemiology ; Female ; Humans ; Hypertension/complications ; Male ; Middle Aged ; Obesity/complications ; Prevalence ; Regression Analysis ; Republic of Korea/epidemiology ; Risk Factors ; Rural Population ; Socioeconomic Factors ; Triglycerides/blood ; Urban Population

BACKGROUND AND OBJECTIVES: Although the standard management of an abdominal aortic aneurysm (AAA) is surgery, endovascular stent-graft treatment is more attractive for patients with significant co-morbid conditions. We evaluated the immediate and mid-term outcomes for the endovascular treatment of AAA. SUBJECTS AND METHODS: Between November 1996 and August 2004, 59 patients with an AAA (53 males, mean age 68.0+/-9.6 years, 3 cases with ruptured AAA) underwent an endovascular stent-graft repair at our institute. All patients were evaluated by an angiography, taken just after the completion of the procedure and at followed up with computed tomography (CT) at 1, 3, 6 and 12 months, and yearly thereafter. RESULTS: Technical success was achieved in 54 of the 59 patients (91.5%). The periprocedural mortality rate was 3.4% (2 of the 59 patients). A primary endoleak was found in 12 patients (20.3%)(type I; 9 patients, type II; 2 patients, type III; 1 patient), 2 of which required subsequent surgical conversion. Spontaneous resolution of an endoleak was seen in 4 patients (33.3%). The average follow-up period of 57 patients was 27.5 months (range from 72 days to 2581 days). In 8 patients (14.0%), a newly developed secondary endoleak was documented. A total 14 patients (23.7%) died during the follow-up period (rupture; 3, operation-related sepsis; 3, unrelated causes; 3, cardiac arrest; 1, unknown causes; 4). The cumulative survival rates at 30 days and at 1 and 2 years were found to be 93.0, and 85.7 and 76.3%, respectively, using Kaplan-Meier methods. Secondary intervention was required in 12 patients (21.8%), and surgical conversion in 4 (6.8%), with 2 (3.4%) requiring conversion to open surgery immediately after the intervention. In those with technical success, without endoleaks and graft failure, the survival rate during follow-up was higher (97.1%; rate with the exception of unrelated cause of death) than that of all the patients. CONCLUSION: The immediate and mid-term results suggest that the endovascular treatment of an AAA is technically feasible and effective. There was higher mortality and morbidity in primary and newly developed endoleak cases; therefore, proper selection of cases, according to the anatomical and clinical criteria, is essential, with meticulous regular follow-ups being critical for the optimal endovascular treatment of an AAA.
Angiography ; Aortic Aneurysm, Abdominal* ; Conversion to Open Surgery ; Endoleak ; Follow-Up Studies ; Heart Arrest ; Humans ; Male ; Mortality ; Sepsis ; Survival Rate ; Transplants ; Treatment Outcome