BACKGROUND: Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is a limited factor in the treatment of non-small-cell lung cancer (NSCLC) patients. Therefore, ongoing studies are trying to identify EGFR-TKIs-resistant mechanisms and to discover novel therapeutic strategies and targets for NSCLC treatment.METHODS: In the present study, the possibility of overcoming intrinsic gefitinib-resistance was examined by regulating the expression of AXL. A natural product-derived antitumor agent, yuanhuadine (YD) was employed to modulate the expression of AXL in the cells.RESULTS: Treatment with YD effectively downregulated AXL expression in AXL-overexpressed gefitinib-resistant H1299 cells. The combination of gefitinib and YD exhibited a synergistic grwoth-inhibitory activity in H1299 cells by downregulation of AXL expression.CONCLUSIONS: Based on these findings, AXL was found to be a promising therapeutic target to overcome the intrinsic resistance to gefitinib in NSCLC. Furthermore, YD is able to effectively regulate the expression of AXL and thus it may be applicable as a potential lead compound for the treatment of gefitinib-resistant NSCLC.
Carcinoma, Non-Small-Cell Lung ; Down-Regulation ; Drug Resistance ; Humans ; Lung Neoplasms ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

Background: This study examined the impact of the performance improvement and patient safety (PIPS) program implemented in 2015 on outcomes for trauma patients in a regional trauma center established by a government-led project for a national trauma system in Korea. Methods: The PIPS program was based on guidelines by the World Health Organization and American College of Surgeons. The corrective strategies were proceeded according to the loop closure principle: data-gathering and monitoring, identification of preventable trauma deaths (PTDs), evaluation of preventable factors, analysis of findings, and corrective action plans. We established guidelines and protocols for trauma care, conducted targeted education and peer review presentations for problematic cases, and enhanced resources for improvement accordingly. A comparative analysis was performed on trauma outcomes over a four-year period (2015–2018) since implementing the PIPS program, including the number of trauma team activation and admissions, time factors related to resuscitation, ventilator duration, and the rate of PTDs. Results: Human resources in the center significantly increased during the period; attending surgeons responsible for trauma resuscitation from 6 to 11 and trauma nurses from 85 to 218. Trauma admissions (from 2,166 to 2,786), trauma team activations (from 373 to 1,688), and severe cases (from 22.6 to 33.8%) significantly increased (all P < 0.001). Time to initial resuscitation and transfusion significantly decreased from 120 to 36 minutes (P < 0.001) and from 39 to 16 minutes (P < 0.001). Time to surgery for hemorrhage control and decompressive craniotomy improved from 99 to 54 minutes (P < 0.001) and 181 to 135 minutes (P = 0.042). Ventilator duration and rate of PTDs significantly decreased from 6 to 4 days (P = 0.001) and 22.2% to 8.4% (P = 0.008). Conclusion Implementation of the PIPS program resulted in improvements in outcomes at a regional trauma center that has just been opened in Korea. Further establishment of the PIPS program is required for optimal care of trauma patients.

Background: This study examined the impact of the performance improvement and patient safety (PIPS) program implemented in 2015 on outcomes for trauma patients in a regional trauma center established by a government-led project for a national trauma system in Korea. Methods: The PIPS program was based on guidelines by the World Health Organization and American College of Surgeons. The corrective strategies were proceeded according to the loop closure principle: data-gathering and monitoring, identification of preventable trauma deaths (PTDs), evaluation of preventable factors, analysis of findings, and corrective action plans. We established guidelines and protocols for trauma care, conducted targeted education and peer review presentations for problematic cases, and enhanced resources for improvement accordingly. A comparative analysis was performed on trauma outcomes over a four-year period (2015–2018) since implementing the PIPS program, including the number of trauma team activation and admissions, time factors related to resuscitation, ventilator duration, and the rate of PTDs. Results: Human resources in the center significantly increased during the period; attending surgeons responsible for trauma resuscitation from 6 to 11 and trauma nurses from 85 to 218. Trauma admissions (from 2,166 to 2,786), trauma team activations (from 373 to 1,688), and severe cases (from 22.6 to 33.8%) significantly increased (all P < 0.001). Time to initial resuscitation and transfusion significantly decreased from 120 to 36 minutes (P < 0.001) and from 39 to 16 minutes (P < 0.001). Time to surgery for hemorrhage control and decompressive craniotomy improved from 99 to 54 minutes (P < 0.001) and 181 to 135 minutes (P = 0.042). Ventilator duration and rate of PTDs significantly decreased from 6 to 4 days (P = 0.001) and 22.2% to 8.4% (P = 0.008). Conclusion Implementation of the PIPS program resulted in improvements in outcomes at a regional trauma center that has just been opened in Korea. Further establishment of the PIPS program is required for optimal care of trauma patients.

Objective: The purpose of this study was to verify the hypothesis, by performing objective measurements, that tongue pressure will have an association with swallowing function in patients with Parkinson’s disease. It was also of interest whether measures of lingual function were consistent with reports of swallowing related quality of life. Methods: The subjects were 18 patients with Parkinson’s disease. Their tongue pressure was examined by using an Iowa oral performance instrument (IOPI). They all underwent video fluoroscopic swallowing study (VFSS) and they completed a Korean swallowing-quality of life questionnaire (K-SWAL-QOL). Tongue pressures were measured in the anterior (MTPa: maximal tongue pressure anterior) and posterior (MTPp: maximal tongue pressure posterior). The cutoff value of MTP was 34 kPa. Results: The average of tongue pressure was decreased in both anterior (MTPa=27.79±13.44 kPa) and posterior (MTPp=19.20±8.88 kPa), and MTPp of all the subjects was less than 34 kPa. For the MTPa, 11 patients were under 34 kPa (abnormal group) and 7 patients were above 34 kPa (normal group). The oral transit time (OTT) of the abnormal MTPa group was significantly delayed more than that of the normal group (P=0.006). On the correlation analysis, the MTPa and OTT, MTPa and penetration aspiration scale (PAS), MTPp and PAS showed significant negative correlations with each other. The MTP and the social, sleep and fatigue subscores of K-SWAL-QOL showed significant positive correlations. Conclusion In patients with Parkinson’s disease, lower tongue pressure was related to delayed oral transit time and a higher aspiration tendency. We expect the clinical usage of the easily measured tongue pressure to predict the swallowing function and help plan the correct treatment.

BACKGROUND: We investigated the rates of fecal transmission of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) among patients admitted to intensive care units (ICUs). METHODS: From June to August 2012, rectal cultures were acquired from all patients at ICU admission. For patients not carrying ESBL-E or CRE at admission, follow-up cultures were performed to detect acquisition. A chromogenic assay was used to screen for ESBL-E and CRE. Bacterial species identification and antibiotic susceptibility tests were performed using the Vitek 2 system (bioMerieux, France). ESBL genotypes were determined by PCR, and clonal relatedness of the isolates was assessed by pulsed-field gel electrophoresis. RESULTS: Out of 347 ICU admissions, 98 patients were found to be carriers of ESBL-E (28.2%, 98/347). Follow-up cultures were acquired from 91 of the patients who tested negative for ESBL-E at admission; the acquisition rate in this group was 12.1% (11/91), although none was a nosocomial transmission. For CRE, the prevalence of fecal carriage was 0.3% (1/347), and the acquisition rate was 2.9% (4/140). None of the CRE isolates were carbapenemase-producers. CONCLUSIONS: The high prevalence of ESBL-E carriage on admission (28.2%), coupled with rare nosocomial transmission and the very low carriage rate of CRE (0.3%), challenge the routine use of active surveillance in non-epidemic settings. Nevertheless, passive surveillance measures, such as rapid and accurate screening of clinical specimens, will be critical for controlling the spread of CRE.
Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/*metabolism ; Carbapenems/*pharmacology ; Carrier State/epidemiology ; Cross Infection/epidemiology/*transmission ; DNA, Bacterial/analysis ; Drug Resistance, Bacterial/drug effects ; Electrophoresis, Gel, Pulsed-Field ; Enterobacteriaceae/enzymology/genetics/*physiology ; Enterobacteriaceae Infections/epidemiology/*transmission ; Feces/*microbiology ; Genotype ; Humans ; Intensive Care Units ; Polymerase Chain Reaction ; Prevalence ; Republic of Korea/epidemiology ; beta-Lactamases/*metabolism

BACKGROUND: We evaluated the analytical and clinical performances of the SD BIOLINE Rota/Adeno Rapid kit (SD Rota/Adeno Rapid; Standard Diagnostics, Inc., Korea), an immunochromatographic assay (ICA), for the simultaneous detection of rotaviruses and adenoviruses in human stool samples. METHODS: We tested 400 clinical stool samples from patients with acute gastroenteritis and compared the ICA results with the results obtained by using ELISA, enzyme-linked fluorescent assays (ELFA), PCR, and multiplex reverse transcription-PCR (mRT-PCR). To assess the analytical performance of the SD BIOLINE Rota/Adeno Rapid kit, we determined its detection limit, reproducibility, cross-reactivity, and analytical reactivity for adenovirus subtypes, and performed interference studies. RESULTS: The overall agreement rates among the tested methods were 91.5% for rotavirus and 85.5% for adenovirus. On the basis of mRT-PCR, the overall agreement, positive agreement, and negative agreement rates of the ICA were 95.6%, 100%, and 94.9% for rotavirus, and 94.0%, 71.4%, and 94.8% for adenovirus, respectively. Using the ICA, we detected all the subtypes of adenovirus tested, but the analytical reactivities for adenovirus subtypes were different between the 4 adenovirus detection methods. The high reproducibility was confirmed, and no cross-reactivity or interference was detected. CONCLUSIONS: The SD BIOLINE Rota/Adeno Rapid kit showed acceptable analytical and clinical performances. However, interpretation of adenovirus positive/negative result should be cautious because of different detectability for adenovirus subtypes among adenovirus detection methods.
Acute Disease ; Adenoviridae/genetics/*immunology/isolation & purification ; Cross Reactions ; DNA, Viral/analysis ; Enzyme-Linked Immunosorbent Assay ; Feces/*virology ; Gastroenteritis/diagnosis/virology ; Humans ; *Immunochromatography ; Multiplex Polymerase Chain Reaction ; RNA, Viral/analysis ; Reagent Kits, Diagnostic ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Rotavirus/genetics/*immunology/isolation & purification

An 82-year-old man with diabetes was admitted to the emergency department with a third-degree burn on his left leg. The deep swab specimen from his left leg was cultured on Sabouraud dextrose agar without cycloheximide and incubated at 25 °C for 5 days. On the basis of morphological characteristics and multigene phylogenetic analyses of the internal transcribed spacer region of ribosomal DNA and partial fragments of beta-tubulin and translation elongation factor 1-alpha, the causal agent of fungal skin infection was identified as Bisifusarium delphinoides, which was newly introduced by accommodating a Fusarium dimerum species complex. Thus, we describe here the first case of skin infection caused by B. delphinoides on a burn patient with diabetes mellitus based on morphological observation and molecular analysis.

BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.
Cefotaxime ; Humans ; Immunization Programs ; Korea ; Levofloxacin ; Multiplex Polymerase Chain Reaction ; Penicillins ; Pneumococcal Vaccines ; Pneumonia ; Serogroup ; Streptococcus pneumoniae ; Streptococcus ; Vaccines