Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Purpose: The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. Materials and Methods: Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. Results: PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). Conclusion Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Purpose: Children have few small alveoli, which reduce lung compliance; in contrast, their cartilaginous rib cage makes their chest wall highly compliant. This combination promotes lung collapse. Prolonged inspiratory to expiratory (I:E) ratio ventilation is used to optimize gas exchange and respiratory mechanics in surgery. However, the optimal ratio is unclear in children. We hypothesized that, compared to a 1:2 I:E ratio, a 1:1 I:E ratio would improve dynamic compliance and oxygenation, and affect the peak airway pressure in pediatric patients undergoing surgery. Materials and Methods: Forty-eight patients aged ≤6 years who were scheduled to undergo surgery under general anesthesia with an arterial line were randomly allocated to receive 1:1 (group 1:1) or 1:2 (group 1:2) I:E ratio ventilation. Airway pressure, respiratory system compliance, and arterial blood gas analyses were compared between groups immediately after induction (T0), 30 min after induction (T1), 60 min after induction (T2), immediately after surgery (T3), and on arrival at the post-anesthesia care unit (T4). Results: Peak and plateau airway pressures were significantly lower in group 1:1 than in group 1:2 at T1 (p=0.044 and 0.048, respectively). The dynamic and static compliances were significantly higher in group 1:1 than in group 1:2 at T1 (p=0.044 and 0.045, respectively). However, the partial pressure of oxygen did not significantly differ between groups. Conclusion Compared to a 1:2 I:E ratio, a 1:1 I:E ratio improved dynamic compliance and lowered the peak airway pressure without complications in pediatric patients. Nevertheless, our results do not support its use solely for improving oxygenation.

Objectives: To investigate the relationship between brain structure and empathy in early adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Nineteen early adolescents with ADHD and 20 healthy controls underwent 3T MRI. All the participants were assessed for different aspects of empathy using measures including the Interpersonal Reactivity Index and Empathy Quotient. Cortical thickness and subcortical structural volume based on T1-weighted scans were analyzed using FreeSurfer. Results: Cognitive empathy (t=-2.52, p=0.016) and perspective taking (t=-2.10, p=0.043) were impaired in the ADHD group compared with the control group. The cluster encompassing the left posterior insular, supramarginal, and transverse temporal cortices [cluster-wise p-value (CWP)=0.001], which are associated with emotional empathy, was significantly smaller in the ADHD group, and the volume of the left nucleus accumbens was greater than that of the control group (F=10.12, p=0.003, effect size=0.22). In the control group, the left superior temporal (CWP=0.002) and lingual cortical (CWP=0.035) thicknesses were positively associated with cognitive empathy, while the right amygdala volume was positively associated with empathic concern (Coef=14.26, t=3.92, p=0.001). However, there was no significant correlation between empathy and brain structure in the ADHD group. Conclusion The ADHD group had a smaller volume of the cortical area associated with emotional empathy than the control group, and there was no brain region showing significant correlation with empathy, unlike in the control group.

Purpose: Children have few small alveoli, which reduce lung compliance; in contrast, their cartilaginous rib cage makes their chest wall highly compliant. This combination promotes lung collapse. Prolonged inspiratory to expiratory (I:E) ratio ventilation is used to optimize gas exchange and respiratory mechanics in surgery. However, the optimal ratio is unclear in children. We hypothesized that, compared to a 1:2 I:E ratio, a 1:1 I:E ratio would improve dynamic compliance and oxygenation, and affect the peak airway pressure in pediatric patients undergoing surgery. Materials and Methods: Forty-eight patients aged ≤6 years who were scheduled to undergo surgery under general anesthesia with an arterial line were randomly allocated to receive 1:1 (group 1:1) or 1:2 (group 1:2) I:E ratio ventilation. Airway pressure, respiratory system compliance, and arterial blood gas analyses were compared between groups immediately after induction (T0), 30 min after induction (T1), 60 min after induction (T2), immediately after surgery (T3), and on arrival at the post-anesthesia care unit (T4). Results: Peak and plateau airway pressures were significantly lower in group 1:1 than in group 1:2 at T1 (p=0.044 and 0.048, respectively). The dynamic and static compliances were significantly higher in group 1:1 than in group 1:2 at T1 (p=0.044 and 0.045, respectively). However, the partial pressure of oxygen did not significantly differ between groups. Conclusion Compared to a 1:2 I:E ratio, a 1:1 I:E ratio improved dynamic compliance and lowered the peak airway pressure without complications in pediatric patients. Nevertheless, our results do not support its use solely for improving oxygenation.

Objectives: To investigate the relationship between brain structure and empathy in early adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Nineteen early adolescents with ADHD and 20 healthy controls underwent 3T MRI. All the participants were assessed for different aspects of empathy using measures including the Interpersonal Reactivity Index and Empathy Quotient. Cortical thickness and subcortical structural volume based on T1-weighted scans were analyzed using FreeSurfer. Results: Cognitive empathy (t=-2.52, p=0.016) and perspective taking (t=-2.10, p=0.043) were impaired in the ADHD group compared with the control group. The cluster encompassing the left posterior insular, supramarginal, and transverse temporal cortices [cluster-wise p-value (CWP)=0.001], which are associated with emotional empathy, was significantly smaller in the ADHD group, and the volume of the left nucleus accumbens was greater than that of the control group (F=10.12, p=0.003, effect size=0.22). In the control group, the left superior temporal (CWP=0.002) and lingual cortical (CWP=0.035) thicknesses were positively associated with cognitive empathy, while the right amygdala volume was positively associated with empathic concern (Coef=14.26, t=3.92, p=0.001). However, there was no significant correlation between empathy and brain structure in the ADHD group. Conclusion The ADHD group had a smaller volume of the cortical area associated with emotional empathy than the control group, and there was no brain region showing significant correlation with empathy, unlike in the control group.

Objectives: We investigated the differences in cognitive and emotional empathic ability between adolescents and adults, and the differences of the brain activation during cognitive and emotional empathy tasks. Methods: Adolescents (aged 13–15 years, n=14) and adults (aged 19–29 years, n=17) completed a range of empathic ability questionnaires and were scanned functional magnetic resonance imaging (fMRI) during both cognitive and emotional empathy task. Differences in empathic ability and brain activation between the groups were analyzed. Results: Both cognitive and emotional empathic ability were significantly lower in the adolescent compared to the adult group. Comparing the adolescent to the adult group showed that brain activation was significantly greater in the right transverse temporal gyrus (BA 41), right insula (BA 13), right superior parietal lobule (BA 7), right precentral gyrus (BA 4), and right thalamus whilst performing emotional empathy tasks. No brain regions showed significantly greater activation in the adolescent compared to the adult group while performing cognitive empathy task. In the adolescent group, scores of the Fantasy Subscale in the Interpersonal Reactivity Index, which reflects cognitive empathic ability, negatively correlated with activity of right superior parietal lobule during emotional empathic situations (r=-0.739, p=0.006). Conclusion These results strongly suggest that adolescents possess lower cognitive and emotional empathic abilities than adults do and require compensatory hyperactivation of the brain regions associated with emotional empathy or embodiment in emotional empathic situation. Compensatory hyperactivation in the emotional empathy-related brain areas among adolescents are likely associated with their lower cognitive empathic ability.

PURPOSE: This study aimed to evaluate the psychometric properties of the Depression Anxiety Stress Scales 21 and 12 in a Korean population. METHODS: The Depression Anxiety Stress Scales were translated into Korean using a translation and backtranslation technique, and the content validity was assessed by an expert panel. Participants were recruited from six community health centers (n = 431) and two community mental health centers (n = 50). A field test of the psychometric properties of the instruments was conducted using confirmatory factor analysis with bootstrap maximum likelihood estimation involving 1,000 samples, Pearson's analysis, t test, and Cronbach's α coefficient. RESULTS: Confirmatory factor analysis of the Depression Anxiety Stress Scales 21 and 12 supported both three-factor and second-order three-factor models. The Scales 21 and 12 satisfied convergent validity with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Perceived Stress Scale-10 and discriminant validity with the Rosenberg Self-Esteem Scale. The scores for the Depression Anxiety Stress Scales 21 and 12 were higher for the psychiatric group than for the nonpsychiatric group, confirming the presence of known-groups validity. The Depression Anxiety Stress Scales 21 and 12 exhibited moderate-to-strong correlations with the Negative Affect. Cronbach's a coefficients for the Depression Anxiety Stress Scales 21 and 12 were .93 and .90, respectively. CONCLUSION: The Depression Anxiety Stress Scales 21 and 12 appear to be acceptable, reliable, and valid instruments. However, the shorter Depression Anxiety Stress Scales 12 may be more feasible to use in a busy practice and also be less burdensome to respondents.
Anxiety ; Community Health Centers ; Community Mental Health Centers ; Depression ; Humans ; Psychometrics ; Surveys and Questionnaires ; Weights and Measures

OBJECTIVES: The purpose of this study was to investigate the differences between adolescents and adults, in the perspective-taking ability, as well as the brain activation patterns during the perspective-taking situation.METHODS: We recruited healthy adolescents aged 13 years to 15 years (n = 20) and adults aged 19 years to 29 years (n = 20). All the subjects were scanned while performing the perspective-taking task, in which an emotional situation was presented in the form of statements comprising first person, as well as third person perspectives. Differences in brain activation between groups were assessed by contrasting neural activity during the tasks.RESULTS: In the between-group analysis, while performing the third-person perspective-taking task, the adolescent group showed greater neural activities in the middle frontal gyrus and precentral gyrus as compared to the adult group. Positive correlation was observed between the activity in the frontal areas (Brodmann area 6/9) and the score of scales related to perspective-taking and social cognition in the adolescent group.CONCLUSIONS: This study suggests that several frontal brain areas of adolescents needs to be overactivated in order to compensate for low perspective-taking ability when they ought to take another person's point of view.
Adolescent ; Adult ; Brain ; Cognition ; Frontal Lobe ; Humans ; Magnetic Resonance Imaging ; Weights and Measures

OBJECTIVES: The purpose of this study was to investigate whether the neural activity of autism spectrum disorder (ASD) patients is different from that of normal individuals when performing aesthetic judgments. METHODS: We recruited typical ASD patients without savant skills (ASD group, n=17) and healthy controls (HC group, n=19) for an functional magnetic resonance imaging study. All subjects were scanned while performing aesthetic judgment tasks on two kinds of artwork (magnificent landscape images and fractal images). Differences in brain activation between the two groups were assessed by contrasting neural activity during the tasks. RESULTS: The aesthetic judgment score for all images was significantly lower in the ASD group than in the HC group. During the aesthetic judgment tasks, the ASD group showed less activation than the HC group in the anterior region of the superior frontal gyrus, and more activation in the temporoparietal area and insula, regardless of the type of images being judged. In addition, during the aesthetic judgment task for the fractal images, the ASD group exhibited greater neural activity in the amygdala and the posterior region of the middle/inferior temporal gyrus (Brodmann area 37) than the HC group. CONCLUSION: The results of this study suggest that the brain activation patterns associated with aesthetic experiences in ASD patients may differ from those of normal individuals.
Amygdala ; Autism Spectrum Disorder* ; Autistic Disorder* ; Beauty* ; Brain ; Fractals ; Humans ; Judgment ; Magnetic Resonance Imaging ; Prefrontal Cortex ; Temporal Lobe