PURPOSE: Recently, after patent ductus arteriosus (PDA) ligation in preterm infants, unexplained hemodynamic instabilities are reported. To determine the incidence, risk factors and clinical manifestations of hemodynamic instability after PDA ligation in very low birth weight (VLBW) infants. METHODS: This retrospective multicenter study enrolled 18 VLBW infants who underwent PDA ligation from January 2002 to February 2008. Hemodynamic instability defined as unexplained cardiopulmonary dysfunction with increased dependency on mechanical ventilation and decreased blood pressure. RESULTS: The mean gestational age and birth weight (BW) of all infants were 27(+)6+/-1(+6) weeks and 951+/-245 g. Hemodynamic instability group (HI) included seven infants (39%) and hemodynamic stability group (HS) included 11 infants (61%). Compared to HS, HI had lower BW (1,033+/-285 g vs. 821+/-126 g, P=0.048) and weight on operation day (1,195+/-404 g vs. 893+/-151 g, P=0.042), longer hospital days (105+/-29 vs. 141+/-39, P=0.038), more severe bronchopulmonary dysplasia (BPD), (no/mild/moderate/severe, 2/5/2/2 vs. 0/1/2/4, P=0.038) and higher preoperative FiO2 (0.29+/-0.06 vs. 0.38+/-0.09, P=0.02). One case of mortality due to sepsis, which was not associated with ligation, was observed among HS. CONCLUSION: The incidence of hemodynamic instability after PDA ligation in VLBW infants was 39%. Low BW, low weight on operation day and preoperative high FiO2 might be risk factors of hemodynamic instability after PDA ligation in VLBW infants. The hemodynamic instability could increase the severity of BPD and hospital days.
Birth Weight ; Bronchopulmonary Dysplasia ; Dependency (Psychology) ; Ductus Arteriosus, Patent ; Gestational Age ; Hemodynamics ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Ligation ; Premature Birth ; Respiration, Artificial ; Retrospective Studies ; Risk Factors ; Sepsis

PURPOSE: Recently, after patent ductus arteriosus (PDA) ligation in preterm infants, unexplained hemodynamic instabilities are reported. To determine the incidence, risk factors and clinical manifestations of hemodynamic instability after PDA ligation in very low birth weight (VLBW) infants. METHODS: This retrospective multicenter study enrolled 18 VLBW infants who underwent PDA ligation from January 2002 to February 2008. Hemodynamic instability defined as unexplained cardiopulmonary dysfunction with increased dependency on mechanical ventilation and decreased blood pressure. RESULTS: The mean gestational age and birth weight (BW) of all infants were 27(+)6+/-1(+6) weeks and 951+/-245 g. Hemodynamic instability group (HI) included seven infants (39%) and hemodynamic stability group (HS) included 11 infants (61%). Compared to HS, HI had lower BW (1,033+/-285 g vs. 821+/-126 g, P=0.048) and weight on operation day (1,195+/-404 g vs. 893+/-151 g, P=0.042), longer hospital days (105+/-29 vs. 141+/-39, P=0.038), more severe bronchopulmonary dysplasia (BPD), (no/mild/moderate/severe, 2/5/2/2 vs. 0/1/2/4, P=0.038) and higher preoperative FiO2 (0.29+/-0.06 vs. 0.38+/-0.09, P=0.02). One case of mortality due to sepsis, which was not associated with ligation, was observed among HS. CONCLUSION: The incidence of hemodynamic instability after PDA ligation in VLBW infants was 39%. Low BW, low weight on operation day and preoperative high FiO2 might be risk factors of hemodynamic instability after PDA ligation in VLBW infants. The hemodynamic instability could increase the severity of BPD and hospital days.
Birth Weight ; Bronchopulmonary Dysplasia ; Dependency (Psychology) ; Ductus Arteriosus, Patent ; Gestational Age ; Hemodynamics ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Ligation ; Premature Birth ; Respiration, Artificial ; Retrospective Studies ; Risk Factors ; Sepsis

PURPOSE: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy (CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. MATERIALS AND METHODS: During concurrent chemoradiotherapy, three or four cycles of gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine (1,200 mg/m2, 1st and 8th day) and cisplatin (60 mg/m2) every three weeks. RESULTS: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range 3m39 months) and the median survival time was 16 months (95% CI; 2.4m39.2 months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). CONCLUSION: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.
Incidence ; Chemoradiotherapy ; Lung Neoplasms

Hydrocarbons are a broad group of organic bodies consisting of hydrogen and carbon. They are commonly found in the environment in the form of gasoline (e.g., butane and propane) and are also used in stain removers, adhesives, lubricants, and a variety of paints. Ingestion of the compound accounts for approximately 3% of all poisoning cases in the United States, but such reports of poisoning are rare in Korea. Hydrocarbon poisoning has many adverse effects. In addition to potentially causing major damage to the respiratory and central nervous systems, direct exposure to hydrocarbons can also cause cardiac arrhythmia, hepatic dysfunction, renal failure, neuropathy, and other injuries. We present the case of a 20-year-old soldier who accidentally ingested a small amount of gasoline. He developed chemical pneumonitis, but recovered with no serious complications.
Adhesives ; Arrhythmias, Cardiac ; Butanes ; Carbon ; Central Nervous System ; Eating ; Gasoline ; Humans ; Hydrocarbons ; Hydrogen ; Korea ; Lubricants ; Military Personnel ; Paint ; Pneumonia ; Renal Insufficiency ; United States ; Young Adult

Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.

OBJECTIVE: To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. MATERIALS AND METHODS: The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin(R))-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. RESULTS: We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. CONCLUSION: Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.
3T3 Cells ; Animals ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/chemistry/*drug therapy ; Cell Line, Tumor ; Drug Delivery Systems/methods ; Female ; Ferric Compounds/chemistry ; Humans ; Liposomes ; Magnetite Nanoparticles/administration & dosage/*chemistry ; Mice ; Molecular Targeted Therapy/methods ; Nanoconjugates/administration & dosage/*chemistry ; Nanoparticles/chemistry ; *Receptor, erbB-2/immunology ; Silicon Dioxide/administration & dosage/*chemical synthesis/chemistry

We report a recent case in which ciprofloxacin-resistant Shigella flexneri was isolated from a 23-yr-old female patient with a history of travel to India. Prior to her admission to our internal medicine department, she experienced symptoms of high fever and generalized weakness from continuous watery diarrhea that developed midway during the trip. S. flexneri was isolated from the stool culture. Despite initial treatment with ciprofloxacin, the stool cultures continued to show S. flexneri growth. In the susceptibility test for antibiotics of the quinolone family, the isolate showed resistance to ciprofloxacin (minimum inhibitory concentration [MIC], 8 microg/mL), norfloxacin (MIC, 32 microg/mL), ofloxacin (MIC, 8 microg/mL), nalidixic acid (MIC, 256 microg/mL), and intermediate resistance to levofloxacin (MIC, 4 microg/mL). In molecular studies for quinolone resistance related genes, plasmid borne-quinolone resistance genes such as qnrA, qnrB, qnrS, aac(6')-Ib-cr, qepA, and oqxAB were not detected. Two mutations were observed in gyrA (248C-->T, 259G-->A) and 1 mutation in parC (239G-->T). The molecular characteristics of the isolated S. flexneri showed that the isolate was more similar to the strains isolated from the dysentery outbreak in India than those isolated from Korea.
Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics/metabolism ; Drug Resistance, Bacterial/drug effects ; Dysentery, Bacillary/microbiology ; Feces/microbiology ; Female ; Humans ; India ; Mutation ; Quinolones/*pharmacology ; Shigella flexneri/drug effects/*isolation & purification/metabolism ; Travel ; Young Adult

Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories—mutations, gene rearrangements, and amplifications—and propose expanded guidelines on molecular testing of lung cancers.
Biomarkers ; Gene Rearrangement ; Humans ; Lung Neoplasms* ; Lung* ; Lymphoma ; Pathology, Molecular ; Phosphotransferases ; Precision Medicine ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

OBJECTIVE: To compare digital breast tomosynthesis (DBT) and conventional full-field digital mammography (FFDM) in the detectability of breast cancers in patients with dense breast tissue, and to determine the influencing factors in the detection of breast cancers using the two techniques. MATERIALS AND METHODS: Three blinded radiologists independently graded cancer detectability of 300 breast cancers (288 women with dense breasts) on DBT and conventional FFDM images, retrospectively. Hormone status, histologic grade, T stage, and breast cancer subtype were recorded to identify factors affecting cancer detectability. The Wilcoxon signed-rank test was used to compare cancer detectability by DBT and conventional FFDM. Fisher's exact tests were used to determine differences in cancer characteristics between detectability groups. Kruskal-Wallis tests were used to determine whether the detectability score differed according to cancer characteristics. RESULTS: Forty breast cancers (13.3%) were detectable only with DBT; 191 (63.7%) breast cancers were detected with both FFDM and DBT, and 69 (23%) were not detected with either. Cancer detectability scores were significantly higher for DBT than for conventional FFDM (median score, 6; range, 0–6; p < 0.001). The DBT-only cancer group had more invasive lobular-type breast cancers (22.5%) than the other two groups (i.e., cancer detected on both types of image [both-detected group], 5.2%; cancer not detected on either type of image [both-non-detected group], 7.3%), and less detectability of ductal carcinoma in situ (5% vs. 16.8% [both-detected group] vs. 27.5% [both-non-detected group]). Low-grade cancers were more often detected in the DBT-only group than in the both-detected group (22.5% vs. 10%, p = 0.026). Human epidermal growth factor receptor-2 (HER-2)-negative cancers were more often detected in the DBT-only group than in the both-detected group (92.3% vs. 70.5%, p = 0.004). Cancers surrounded by mostly glandular tissue were detected less often in the DBT only group than in the both-non-detected group (10% vs. 31.9%, p = 0.016). DBT cancer detectability scores were significantly associated with cancer type (p = 0.012), histologic grade (p = 0.013), T and N stage (p = 0.001, p = 0.024), proportion of glandular tissue surrounding lesions (p = 0.013), and lesion type (p < 0.001). CONCLUSION: Invasive lobular, low-grade, or HER-2-negative cancer is more detectable with DBT than with conventional FFDM in patients with dense breasts, but cancers surrounded by mostly glandular tissue might be missed with both techniques.
Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Epidermal Growth Factor ; Female ; Humans ; Mammography* ; Retrospective Studies

OBJECTIVE: To compare the diagnostic performance and interobserver variability of strain ratio obtained from one or two regions of interest (ROI) on breast elastography.MATERIALS AND METHODS: From April to May 2016, 140 breast masses in 140 patients who underwent conventional ultrasonography (US) with strain elastography followed by US-guided biopsy were evaluated. Three experienced breast radiologists reviewed recorded US and elastography images, measured strain ratios, and categorized them according to the American College of Radiology breast imaging reporting and data system lexicon. Strain ratio was obtained using the 1-ROI method (one ROI drawn on the target mass), and the 2-ROI method (one ROI in the target mass and another in reference fat tissue). The diagnostic performance of the three radiologists among datasets and optimal cut-off values for strain ratios were evaluated. Interobserver variability of strain ratio for each ROI method was assessed using intraclass correlation coefficient values, Bland–Altman plots, and coefficients of variation.RESULTS: Compared to US alone, US combined with the strain ratio measured using either ROI method significantly improved specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve (AUC) (all p values < 0.05). Strain ratio obtained using the 1-ROI method showed higher interobserver agreement between the three radiologists without a significant difference in AUC for differentiating breast cancer when the optimal strain ratio cut-off value was used, compared with the 2-ROI method (AUC: 0.788 vs. 0.783, 0.693 vs. 0.715, and 0.691 vs. 0.686, respectively, all p values > 0.05).CONCLUSION: Strain ratios obtained using the 1-ROI method showed higher interobserver agreement without a significant difference in AUC, compared to those obtained using the 2-ROI method. Considering that the 1-ROI method can reduce performers' efforts, it could have an important role in improving the diagnostic performance of breast US by enabling consistent management of breast lesions.