A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). @*Materials and Methods@#Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. @*Results@#RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). @*Conclusion@#GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China through a drug-target interaction deep learning model

The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV.

Prevalence of extracardiac findings in the evaluation of ischemic heart disease by multidetector computed tomography / 老年心脏病学杂志（英文版）

Objective Multidector computed tomography (MDCT) is now commonly used for the evaluation of coronary artery disease. Because MDCT images include many non-cardiac organs and the patient population evaluated is highly susceptible to extracardiac diseases, this study was designed to evaluate the prevalence of extracardiac findings in the MDCT evaluation of ischemic heart disease. Methods From March 2007 to March 2008, a total of six-hundred twenty patients, who underwent 64-slice MDCT evaluations for chest pain, or dyspnea, were enrolled in this study. Cardiac and non-cardiac findings were comprehensively evaluated by a radiologist. Results Enrolled patients included 306 men (49.4%), with a mean age of 66 years. Significant coronary artery stenosis was found in 41.6%of the patients. A total of 158 extracardiac findings were observed in 110 (17.7%) patients. Commonly involved extracardiac organs were lung (36.7%), hepatobiliary system (21.5%), thyroid (19.6%), kidney (10.8%), spine (9.7%) and breast (0.6%). Of those 110 patients, 50 (45.5%) patients underwent further diagnostic investigations. Malignant disease was detected in three (2.7%) patients (lung cancer, pancreatic cancer, and thyroid cancer). Conclusions Extracardiac findings are frequently present and should be a concern in the MDCT evaluation of chest pain syndrome.

Partially Cystic Thyroid Nodules: Ultrasound Findings of Malignancy

OBJECTIVE: To seek for the ultrasound (US) findings of partially cystic thyroid nodules that are associated with malignancy. MATERIALS AND METHODS: We reviewed the US characteristics of 22 surgically confirmed partially cystic papillary carcinomas, and compared them with those of 80 benign partially cystic nodules. The review cases were selected in a random order from a total of 1029 partially cystic nodules that were diagnosed with an US-guided fine needle aspiration biopsy over a period of 8 years (June 2003 to October 2010) at our institution. RESULTS: In partially cystic thyroid nodules, a taller-than-wide shape (100%, p < 0.001) and spiculated or microlobulated margin (58.3%, p = 0.003) were significantly associated with malignancy. In terms of internal solid portion of the nodule, eccentric configuration (68.0%, p < 0.001), non-smooth margin (81.3%, p < 0.001), hypoechogenecity (30.0%, p < 0.042), and microcalcification (89.5%, p < 0.001) were more frequently demonstrated in malignant nodules than benign ones. CONCLUSION: In partially cystic thyroid nodules, understanding the characteristics of US findings is important to make a precise diagnosis of malignant nodules.

Ultrasonographic Findings of an Implanted Absorbable Mesh in Patients with Breast Partial Resection: a Preliminary Study

PURPOSE: To present the ultrasonographic findings of an implanted absorbable mesh in patients who underwent breast partial resection. MATERIALS AND METHODS: We retrospectively analyzed the ultrasonographic findings of 18 patients who underwent breast partial resection with an absorbable mesh implant to minimize the breast deformity. Sonography was performed approximately 3 months after surgery (mean interval, 92 days). The presence of a capsule and cyst at the surgical site, the size of the cyst, internal content of the cyst, vascularity of the lesion, and presence of complications were analyzed. RESULTS: An ultrasound examination revealed a well-encapsulated cyst with regular capsule in 16 of the 18 patients. The longest diameter of the cyst varied from 3 cm to 10 cm. Among 16 cases that showed a well-encapsulated cyst, 11 cases showed an isoechoic nodular pattern in the cyst and in the remaining five cases, the internal nodular pattern was not seen. In two of the18 cases, an isoechoic nodular pattern without fluid content was seen for the lesions. A Doppler study revealed no vascularity in any of the lesions. CONCLUSION: Ultrasonographic findings of an implanted absorbable mesh, inserted in the surgical site to minimize breast deformity in patients that underwent breast partial resection, showed the presence of a well-encapsulated cyst with an internal isoechoic nodular pattern in the majority of the cases.

The Effect of Nutrition Education Program in Physical Health, Nutritional Status and Health-Related Quality of Life of the Elderly in Seoul

This study was performed to investigate the effects of nutrition education program in physical health, nutritional status and health-related quality of life (HRQoL )of the Elderly in Seoul. Nutrition education program was consisted of healthy eating, prevention and diet therapy of obesity, diabetes, cardiovascular disease, and osteoporosis. Seventy eight free-living elderly people (13 male, 65 female ), aged > or =60 years participated in this program. Before and after nutri-tion education program, we surveyed the general characteristics, physical health, general health, nutrition status, and health-related quality of life to the subjects. All the subjects were divided into program completers (N =47 )and non-completers (N =31 ). All the data were analyzed by student t-test, chi-square test, paired t-test, and marginal homo-geneity test using SPSS 9.0 version at p <0.05. After nutrition education program, physical activity and ADL maintained, however IADL improved in program noncompleters. In eating habits, 'slow eating' significantly improved in program completers in program completers. Nutrition knowledge and recognition scores were significantly increased in both groups, and accuracy score was significantly increased in program completers. However, nutrient-intakes of %RDA were not significantly changed in both groups, and it seemed to be more influenced by other factors such as 'family income' or 'family type' than by the nutrition education program. In HRQoL, social functioning was improved after nutrition education program in both groups (p <0.05 ). The nutrition education program has more effects on the pro-gram completers than on the noncompleters, and it is also needed social supports for the Elderly to fulfill their nutrient requirements.

Evaluation of Functional Ability and Nutritional Risk according to Self-Rated Health (SRH) of the Elderly in Seoul and Kyunggi-do

A functional ability and adequate nutritional status are the major determinants of health status. Self-rated health (SRH) is a worldwide method to assess health status and it is recognized as a predictor of morbidity and mortality in the elderly. This study was designed to evaluate the functional ability and nutritional risk according to SRH in the elderly. Four hundred nine free-living elderly people (118 male, 291 female), aged > or = 65 years were interviewed by trained interviewers using structured questionnaires including demographic information, SRH, anthropometric measurements, functional ability, general health status, and nutritional risk. SRH was divided into three status such as "Good", "Moderate" and "Poor" status. And all the data were analyzed by oneway ANOVA , spearman correlation, and x(2) analysis using SPSS 9.0 version at p < 0.05. Of all the subjects, 48.9% perceived their health status as "poor", and their functional abilities (activities of daily living, instrumental activities of daily living) were more impaired than their counterparts' ("good" and "moderate"). Poor self-rated health was also related to: a higher prevalence of illnesses (p < 0.001) especially in hypertension, arthritis. Self-rated health was significantly related to food security (p < 0.001), food enjoyment (p < 0.001),and nutritional knowledge (p = 0.013). Also NSI checklist total score was the highest in "poor" health status (p < 0.001). Better self-rated health was related to better food security, and better food enjoyment. However, smoking, alcoholic intake, exercise, eating behaviors, and demographic characteristics were not significantly different among the three SRH status. SRH was closely related to chronic diseases, functional ability, and nutritional risk in the elderly. Therefore, public health strategies for the elderly should be focused on the elderly who are "poor" in SRH, to improve nutritional status and functional ability, and to reduce risk factors of chronic diseases.