Seon Woo Kim

Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy ☆

PURPOSE Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with locally advanced, metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations (female, adenocarcinoma histology, and never-smoker) were eligible. RESULTS A total of 96 (48 per arm) patients were randomly assigned to gefitinib- or erlotinib-arm, respectively. Baseline characteristics were well-balanced between the two arms. The response rates (RR) were 47.9% in the gefitinib arm and 39.6% in the erlotinib arm. Median PFS was 4.9 months (95% CI, 1.3-8.5) in the gefitinib arm and 3.1 months (95% CI, 0.0-6.4) in the erlotinib arm. The most common grade 3/4 toxicity was skin rash. Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm (RR (%) 47.9 vs. 39.6, p=0.269; median survival (months) 4.9 vs. 3.1, p=0.336). There was no significant difference in QOL between the two arms. CONCLUSION Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC. We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population.

Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutrition Examination Survey

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010–2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17–2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24–3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05–3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05–2.77), depression (OR 2.38, 95% CI 1.47–3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15–4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.

Genomic and Evolutionary Analysis of Two Salmonella enterica Serovar Kentucky Sequence Types Isolated from Bovine and Poultry Sources in North America

Salmonella enterica subsp. enterica serovar Kentucky is frequently isolated from healthy poultry and dairy cows and is occasionally isolated from people with clinical disease. A genomic analysis of 119 isolates collected in the United States from dairy cows, ground beef, poultry and poultry products, and human clinical cases was conducted. Results of the analysis demonstrated that the majority of poultry and bovine-associated S. Kentucky were sequence type (ST) 152. Several bovine-associated (n = 3) and food product isolates (n = 3) collected from the United States and the majority of human clinical isolates were ST198, a sequence type that is frequently isolated from poultry and occasionally from human clinical cases in Northern Africa, Europe and Southeast Asia. A phylogenetic analysis indicated that both STs are more closely related to other Salmonella serovars than they are to each other. Additionally, there was strong evidence of an evolutionary divergence between the poultry-associated and bovine-associated ST152 isolates that was due to polymorphisms in four core genome genes. The ST198 isolates recovered from dairy farms in the United States were phylogenetically distinct from those collected from human clinical cases with 66 core genome SNPs differentiating the two groups, but more isolates are needed to determine the significance of this distinction. Identification of S. Kentucky ST198 from dairy animals in the United States suggests that the presence of this pathogen should be monitored in food-producing animals.

Evaluation of Audiometric Test Results to Determine Hearing Impairment in Patients with Rheumatoid Arthritis: Analysis of Data from the Korean National Health and Nutrition Examination Survey

This study aimed to evaluate the association between rheumatoid arthritis (RA) and hearing impairment in the Korean adult population. Audiometric and laboratory test data from the 2010–2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. The relationship between RA and hearing impairment was analyzed, adjusting for various known risk factors associated with hearing impairment. RA was defined in the questionnaire as “RA diagnosed by a physician (yes/no) through a standardized interview.” We defined hearing impairment according to 2 categories of frequency (low/mid and high) as follows (average values in kHz): low/mid frequency, 0.5, 1.0, and 2.0, and high frequency, 3.0, 4.0, and 6.0. Of the subjects, 15,158 (weighted n = 32,035,996) completed the audiometric tests. The overall weighted prevalence of RA was 1.5%. The prevalence of hearing impairment was higher in the subjects with RA than in those without RA, in both, the low/mid- and high-frequency categories (21.1% vs 7.5%, p < 0.001 and 43.3% vs. 26.2%, p < 0.001, respectively). In the multivariable logistic analysis, RA (odds ratios [OR] 1.47, 95% confidence interval [CI] 1.05–2.06, p = 0.025) was an independent risk factor of low/mid-frequency hearing impairment along with age (OR 1.12, 95% CI 1.12–1.13, p < 0.001), current smoking (OR 1.27, 95% CI 1.03–1.56, p = 0.026), and college graduation (OR 0.53, 95% CI 0.39–0.72, p < 0.001). In the multivariable analysis of high-frequency hearing impairment, RA did not show any association with hearing impairment. This study suggests that RA is associated with low/mid-frequency hearing impairment after adjustment for various known risk factors. Further study is needed to verify the hearing impairment in RA.

Prevalence and associated factors of facial palsy and lifestyle characteristics: data from the Korean National Health and Nutrition Examination Survey 2010–2012

Objectives To report the nationwide prevalence of facial palsy (FP) of grade III or worse in the House–Brackmann (H–B) grading system in South Korea and assess the associated factors. Design Cross-sectional analysis of a nationwide health survey. Settings South Korea. Methods We obtained data from the 2010 to 2012 Korea National Health and Nutrition Examination Surveys, which were cross-sectional surveys of the South Korean civilian population living in households and aged ≥1 year (N=23 533). A field survey team performed interviews, physical examinations and laboratory tests. Facial expression was evaluated based on the H–B grading system. Results Among the population aged ≥1 year, the prevalence of FP of grade III or worse in the H–B grading system was 0.12% (95% CI 0.07% to 0.17%). FP was more prevalent in women (p=0.01) and the prevalence rate increased with age (p<0.001). In participants aged ≥19 years, age, female gender, history of cardiovascular disease and the serum total cholesterol level were associated with FP in a multivariable analysis. In the evaluation of lifestyle, the individuals with FP had a higher rate of depressive mood and were more restricted in their daily activities. Conclusions Considering the significance of facial expression in psychosocial activities, public acknowledgement and further intervention are required to support patients with this distressing condition.

Genetic diversity and virulence profiles of Listeria monocytogenes recovered from bulk tank milk, milk filters, and milking equipment from dairies in the United States (2002 to 2014)

Unpasteurized dairy products are known to occasionally harbor Listeria monocytogenes and have been implicated in recent listeriosis outbreaks and numerous sporadic cases of listeriosis. However, the diversity and virulence profiles of L. monocytogenes isolates recovered from these products have not been fully described. Here we report a genomic analysis of 121 L. monocytogenes isolates recovered from milk, milk filters, and milking equipment collected from bovine dairy farms in 19 states over a 12-year period. In a multi-virulence-locus sequence typing (MVLST) analysis, 59 Virulence Types (VT) were identified, of which 25% were Epidemic Clones I, II, V, VI, VII, VIII, IX, or X, and 31 were novel VT. In a multi-locus sequence typing (MLST) analysis, 60 Sequence Types (ST) of 56 Clonal Complexes (CC) were identified. Within lineage I, CC5 and CC1 were among the most abundant, and within lineage II, CC7 and CC37 were the most abundant. Multiple CCs previously associated with central nervous system and maternal-neonatal infections were identified. A genomic analysis identified variable distribution of virulence markers, Listeria pathogenicity islands (LIPI) -1, -3, and -4, and stress survival island-1 (SSI-1). Of these, 14 virulence markers, including LIPI-3 and -4 were more frequently detected in one lineage (I or II) than the other. LIPI-3 and LIPI-4 were identified in 68% and 28% of lineage I CCs, respectively. Results of this analysis indicate that there is a high level of genetic diversity among the L. monocytogenes present in bulk tank milk in the United States with some strains being more frequently detected than others, and some being similar to those that have been isolated from previous non-dairy related outbreaks. Results of this study also demonstrate significant number of strains isolated from dairy farms encode virulence markers associated with severe human disease.

Comorbidities and health-related quality of life in Koreans with knee osteoarthritis: Data from the Korean National Health and Nutrition Examination Survey (KNHANES).

Objectives This study aimed to evaluate the association of knee osteoarthritis (OA) with comorbidities and health-related quality of life (HRQOL). Methods A total of 8,907 (weighted n = 13,687,058) participants aged ≥50 years who had undergone knee radiography were selected from the 2010–2012 Korea National Health and Nutrition Examination Survey. OA was classified into four subgroups based on the presence or absence of pain and radiographic OA (ROA): non-OA (Pain-/ROA-), pain only (Pain+/ROA-), ROA only (Pain-/ROA+), and painful ROA (Pain+/ROA+). ROA was defined as Kellgren–Lawrence grade ≥ 2. HRQOL measurements including EuroQOL visual analogue scale (EQ-VAS) scores and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D index) were also analyzed. Multivariable logistic regression and linear regression analyses were performed. Results After adjustment for socioeconomic and lifestyle characteristics, cardiovascular disease, malignancy, and other comorbidities were not significantly associated with OA. Pain only and painful ROA were each significantly associated with limitations in physical activity (odds ratio (OR) 2.66, 95% CI 2.07–3.44, p < 0.001 and OR 2.83, 95% CI 2.25–3.58, p < 0.001, respectively), lower EQ-VAS (β-coefficient = -10.95, p < 0.001 and β-coefficient = -9.75, p < 0.001, respectively), and EQ-5D index (β-coefficient = -0.10, p < 0.001 and β-coefficient = -0.13, p < 0.001) compared with the non-OA group, whereas ROA only was not associated with limitations in physical activity or lower HRQOL score. Conclusions Comorbidities were not significantly associated with knee OA after adjustment. Knee OA was associated with physical activity and HRQOL. Painful knee OA, with or without ROA, was more strongly associated with decreased physical activity and lower quality of life than ROA without pain.

Genome Sequences of Two Salmonella enterica Serovar Kentucky Isolates Recovered from Poultry Carcasses in the United States

ABSTRACT We report here the draft genome sequences of two Salmonella enterica serovar Kentucky eBurstGroup 15 isolates collected from poultry carcasses in Georgia (USA).

The Outcomes of Hypertransfusion in Major ABO Incompatible Allogeneic Stem Cell Transplantation

Major ABO incompatibility may be potentially associated with immediate or delayed hemolysis and delayed onset of erythropoiesis in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To determine if hemolysis can be prevented by the inhibition of graft erythropoiesis, we performed hypertransfusion and assessed red cell transfusion requirement and independence. Between October 1995 and December 2001, 28 consecutive patients receiving major ABO incompatible HSCT at Samsung Medical Center were hypertransfused to maintain their hemoglobin levels at 15 g/dL or more. We retrospectively compared the outcomes of these patients with those of 47 patients at Asan Medical Center whose target hemoglobin levels were 10 g/dL. Reticulocyte engraftment was significantly delayed in hypertransfused group (51 days vs. 23 days; p=.001). There was no significant difference in the total amount of red cells transfused within 90 days post-HSCT (25 units vs. 26 units; p=.631). No significant difference in the time to red cell transfusion independence was observed between the two groups (63 days vs. 56 days; p=.165). In conclusion, we failed to improve red cell transfusion requirement and independence in major ABO incompatible HSCT with hypertransfusion.