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: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

There is a growing interest in developing new biomarkers using digital devices. The primary purpose of digital biomarkers is to obtain features based on multi-dimensional data such as multiple data sources from various digital devices and time-series data reflecting temporal changes. Therefore, digital biomarkers can be used to measure the behavioral patterns of individuals in their daily lives in contrast to traditional biomarkers that reflect specific time points in clinical or laboratory settings. However, there are still several limitations including validation and interpretation. This article reviews the potential of digital biomarkers, explores previous studies on digital phenotypes related to Alzheimer’s disease, and discusses the future challenges of implementing digital biomarkers in the medical field.

Purpose: We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. Materials and Methods: This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. Results: Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36–5.13] and major CHDs (aOR 7.30; 95% CI 3.18–15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42–12.46) was associated with non-chromosomal major CHDs. Conclusion Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

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.

Background: People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. Methods: We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. Results: Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. Conclusion Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

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

Acute vestibular neuritis (VN) is characterized by acute/subacute vertigo with spontaneous nystagmus and unilateral loss of semicircular canal function. Vestibular system in human is represented in the brain bilaterally with functional asymmetries of the right hemispheric dominance in the right handers. Spatial working memory entails the ability to keep spatial information active in working memory over a short period of time which is also known as the right hemispheric dominance. Three patients (patient 1, 32-year-old female; patient 2, 18-year-old male; patient 3, 63-year-old male) suffered from acute onset of severe vertigo, nausea and vomiting. Patients 1 and 2's examination revealed VN on the right side showing spontaneous left beating nystagmus and impaired vestibular ocular reflex on the right side in video head-impulse and caloric tests. Patient 3's finding was fit for VN on the left side. We also evaluated visuospatial memory function with the block design test in these 3 VN patients which discovered lower scores in patients 1 and 2 and the average level in patient 3 compare to those of healthy controls. Follow-up block design test after resolved symptoms showed within normal range in both patients. Our cases suggest that the patients with unilateral peripheral vestibulopathy may have an asymmetrical effect on the higher vestibular cognitive function. The right VN can be associated with transient visuospatial memory dysfunction. These findings add the evidence of significant right hemispheric dominance for vestibular and visuospatial structures in the right-handed subjects, and of predominant dysfunction in the hemisphere ipsilateral to the peripheral lesion side.
Adolescent ; Adult ; Brain ; Caloric Tests ; Cognition ; Female ; Follow-Up Studies ; Humans ; Male ; Memory ; Memory, Short-Term ; Middle Aged ; Nausea ; Reference Values ; Reflex ; Semicircular Canals ; Vertigo ; Vestibular Neuronitis ; Vomiting

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements.
Adenosine ; Anticarcinogenic Agents ; Atrophy ; Brain ; Brain Diseases ; Cardiovascular Diseases ; Complementary Therapies ; Disease Management ; Fruit ; Heart ; Inflammation ; Insulin ; Liver ; Liver Diseases ; Muscle, Skeletal ; Oxidants ; Protein Kinases ; Vegetables

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