[show abstract][hide abstract] ABSTRACT: Background and Purpose—Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. We investigated the clinical and radiological effects of therapeutic hypothermia in acute ischemic stroke patients after recanalization.
Methods—A prospective cohort study at 2 stroke centers was performed. We enrolled patients with acute ischemic stroke in the anterior circulation with an initial National Institutes of Health Stroke Scale ≥10 who had successful recanalization (≥thrombolysis in cerebral ischemia, 2b). Patients at center A underwent a mild hypothermia (34.5°C) protocol, which included mechanical ventilation, and 48-hour hypothermia and 48-hour rewarming. Patients at center B were treated according to the guidelines without hypothermia. Cerebral edema, hemorrhagic transformation, good outcome (3-month
modified Rankin Scale, ≤2), mortality, and safety profiles were compared. Potential variables at baseline and during the therapy were analyzed to evaluate for independent predictors of good outcome.
Results—The hypothermia group (n=39) had less cerebral edema (P=0.001), hemorrhagic transformation (P=0.016), and better outcome (P=0.017) compared with the normothermia group (n=36). Mortality, hemicraniectomy rate, and medical
complications were not statistically different. After adjustment for potential confounders, therapeutic hypothermia (odds ratio, 3.0; 95% confidence interval, 1.0–8.9; P=0.047) and distal occlusion (odds ratio, 7.3; 95% confidence interval; 1.3–40.3; P=0.022) were the independent predictors for good outcome. Absence of cerebral edema (odds ratio, 5.4;
95% confidence interval, 1.6–18.2; P=0.006) and no medical complications (odds ratio, 9.3; 95% confidence interval, 2.2–39.9; P=0.003) were also independent predictors for good outcome during the therapy.
Conclusions—In patients with ischemic stroke, after successful recanalization, therapeutic hypothermia may reduce risk of cerebral edema and hemorrhagic transformation, and lead to improved clinical outcomes
[show abstract][hide abstract] ABSTRACT: This study aims to identify clinical case definitions of influenza with higher accuracy in patients stratified by age group and influenza activity using hospital-based surveillance system.
In seven tertiary hospitals across South Korea during 2011-2012 influenza season, respiratory specimens were obtained from patients presenting an influenza-like illness (ILI), defined as having fever plus at least one of following symptoms: cough, sore throat or rhinorrhea. Influenza was confirmed by reverse transcriptase-polymerase chain reaction. We performed multivariate logistic regression analyses to identify clinical variables with better relation with laboratory-confirmed influenza, and compared the accuracy of combinations.
Over the study period, we enrolled 1417 patients, of which 647 had laboratory-confirmed influenza. Patients with cough, rhinorrhea, sore throat or headache were more likely to have influenza (p<0.05). The most accurate criterion across the study population was the combination of cough, rhinorrhea, sore throat and headache (sensitivity 71.3%, specificity 60.1% and AUROC 0.66). The combination of rhinorrhea, sore throat and sputum during the peak influenza activity period in the young age group showed higher accuracy than that using the whole population (sensitivity 89.3%, specificity 72.1%, and AUROC 0.81).
The accuracy of clinical case definitions of influenza differed across age groups and influenza activity periods. Categorizing the entire population into subgroups would improve the detection of influenza patients in the hospital-based surveillance system.
PLoS ONE 01/2014; 9(1):e84873. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. We investigated the clinical and radiological effects of therapeutic hypothermia in acute ischemic stroke patients after recanalization.
A prospective cohort study at 2 stroke centers was performed. We enrolled patients with acute ischemic stroke in the anterior circulation with an initial National Institutes of Health Stroke Scale ≥10 who had successful recanalization (≥thrombolysis in cerebral ischemia, 2b). Patients at center A underwent a mild hypothermia (34.5°C) protocol, which included mechanical ventilation, and 48-hour hypothermia and 48-hour rewarming. Patients at center B were treated according to the guidelines without hypothermia. Cerebral edema, hemorrhagic transformation, good outcome (3-month modified Rankin Scale, ≤2), mortality, and safety profiles were compared. Potential variables at baseline and during the therapy were analyzed to evaluate for independent predictors of good outcome.
The hypothermia group (n=39) had less cerebral edema (P=0.001), hemorrhagic transformation (P=0.016), and better outcome (P=0.017) compared with the normothermia group (n=36). Mortality, hemicraniectomy rate, and medical complications were not statistically different. After adjustment for potential confounders, therapeutic hypothermia (odds ratio, 3.0; 95% confidence interval, 1.0-8.9; P=0.047) and distal occlusion (odds ratio, 7.3; 95% confidence interval; 1.3-40.3; P=0.022) were the independent predictors for good outcome. Absence of cerebral edema (odds ratio, 5.4; 95% confidence interval, 1.6-18.2; P=0.006) and no medical complications (odds ratio, 9.3; 95% confidence interval, 2.2-39.9; P=0.003) were also independent predictors for good outcome during the therapy.
In patients with ischemic stroke, after successful recanalization, therapeutic hypothermia may reduce risk of cerebral edema and hemorrhagic transformation, and lead to improved clinical outcomes.
[show abstract][hide abstract] ABSTRACT: There is a lack of targeted studies to validate the effectiveness of influenza vaccination on the reduction in influenza-related hospitalizations among patients with co-morbidities. In this study, we estimate the effectiveness of influenza vaccination on preventing hospitalizations in persons with cardiopulmonary disease and establish an evidence base for recommendations on influenza vaccination in this population. During the influenza epidemic in 2011-2012, we performed a multicenter, retrospective case-control study. Cases were patients hospitalized due to acute exacerbation of asthma, COPD, ischemic heart disease (IHD), and congestive heart failure (CHF). Controls were selected from outpatients who visited study hospitals but who were not hospitalized. Cases and controls were matched 1:1 based on age, gender, and date of hospital visit. Conditional logistic regression analyses were used to determine the effectiveness of vaccination. Between 25 December 2011 and 5 May 2012, 828 of each hospitalized and control subjects were identified. The influenza vaccination rate of the hospitalized and non-hospitalized patients was 54.2% and 60.4%, respectively (P = 0.006). The overall vaccine effectiveness for preventing hospitalization was 33.7% [95% confidence interval (CI) 14.0-49.0%; P = 0.002]. Conditional logistic regression analysis showed that influenza vaccination significantly reduced the risk of hospitalization, especially due to acute exacerbation of IHD and CHF, in patients aged 65 y and older. The estimated vaccine effectiveness in these patients was 56.0% (95% CI 32.1-71.4%, P = 0.002). Influenza vaccination was associated with a reduction in the risk of hospitalization due to acute exacerbation of cardiopulmonary disease. We recommend the vaccine be given primarily to patients with underlying cardiovascular disease, particularly those 65 y of age and older.
Human vaccines & immunotherapeutics. 10/2013; 10(2).
[show abstract][hide abstract] ABSTRACT: This study investigated whether epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) increase the development of leptomeningeal metastasis (LM) compared with standard chemotherapy in EGFR mutation-enriched non- small cell lung cancer. The incidence of LM was longitudinally assessed in never smokers with advanced adenocarcinoma of the lung enrolled in a phase III randomized controlled study that compared gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy (The First-SIGNAL study). Among 203 patients who were enrolled at the National Cancer Center Hospital (Goyang, Republic of Korea), LM occurred in 32 (15.8 %) with a minimum follow-up time of 55.1 months. The 1-, 2-, and 3-year actuarial incidence rates of LM were 5.3, 10.6, and 24.6 %, respectively. During first-line treatment, LM occurred in 2 patients (2.0 %) treated with gefitinib and in 3 patients (3.2 %) treated with GP. There was no difference in the incidence of LM during first-line treatment between the two groups (P = 0.934). The incidence of LM was significantly increased during second-line EGFR-TKI treatment compared with first-line EGFR-TKI treatment (P = 0.041). During the disease course, the cumulative incidence of LM was not significantly different between the two treatment groups (P = 0.514). The median time to LM was 21.4 and 24.0 months in the gefitinib and GP groups, respectively (P = 0.895). Similar trends were observed in the subset analysis with 23 EGFR-mutant patients. In conclusion, LM predominantly occurred in the late phase of disease in this population. EGFR-TKIs did not affect the incidence or timing of LM development.
Journal of Neuro-Oncology 07/2013; · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. METHODS: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m(2) on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m(2) on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779. FINDINGS: From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2-8·3], vs 6·0 months [5·6-7·1], hazard ratio [HR] 0·57 [0·47-0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3-20·8) and 15·2 months (12·7-17·5), respectively (HR 0·79 [0·64-0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9-20·4] vs 6·9 months [5·3-7·6], HR 0·25 [0·16-0·39]; p<0·0001; median overall survival 31·4 months [22·2-undefined], vs 20·6 months [14·2-26·9], HR 0·48 [0·27-0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). INTERPRETATION: Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. FUNDING: F Hoffmann-La Roche.
The lancet oncology 06/2013; · 14.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults. METHODS: This multicenter, retrospective cohort study was designed to estimate the clinical and economic burden of IPD in adults over the last decade. Data were collected from patients with IPD at 10 university hospitals in South Korea. We estimated the proportion of IPD among all hospitalized patients, the case fatality rate, and the direct medical costs of IPD. Data were further analyzed according to age and risk groups. RESULTS: During the study period, 970 patients with IPD were identified. The mean age for all patients was 60.9 years; patients aged 50--64 years (33.0%) were most numerous, followed by those aged 65--74 years (27.4%). Overall, the proportion of IPD was 0.36 cases/1000 hospitalized patients and the case fatality rate was 30.9%, which increased significantly with age (p < 0.01). The mean direct medical costs were estimated to be US $7,452 without a difference between age and risk groups. On multivariate analysis, old age, advanced ECOG performance status, bacteremic pneumonia, and nosocomial infection were independent risk factors of 30-day case fatality. CONCLUSIONS: The clinical disease burden of IPD increased significantly with age and direct medical costs from IPD were substantial, regardless of age and co-morbid conditions. The current age-based vaccination strategy appears to be appropriate.
[show abstract][hide abstract] ABSTRACT: The aim of the current Part II of Stroke Statistics in Korea is to summarize nationally representative data on public awareness, pre-hospital delay, thrombolysis, and quality of acute stroke care in a single document. The public's knowledge of stroke definition, risk factors, warning signs, and act on stroke generally remains low. According to studies using open-ended questions, the correct definition of stroke was recognized in less than 50%, hypertension as a stroke risk factor in less than 50%, and other well-defined risk factors in less than 20%. Among stroke warning signs, sudden paresis or numbness was best appreciated, with recognition rates ranging in 36.9-73.7%, but other warning signs including speech disturbance were underappreciated. In addition, less than one third of subjects in a representative population survey were aware of thrombolysis and had knowledge of the appropriate act on stroke, calling emergency medical services (EMS). Despite EMS being an essential element in the stroke chain of survival and outcome improvement, EMS protocols for field stroke diagnosis and prehospital notification for potential stroke patients are not well established. According to the Assessment for Quality of Acute Stroke Care, the median onset-to-door time for patients arriving at the emergency room was 4 hours (mean, 17.3 hours) in 2010, which was not reduced compared to 2005. In contrast, the median door-to-needle time for intravenous tissue plasminogen activator (IV-TPA) treatment was 55.5 minutes (mean, 79.5 minutes) in 2010, shorter than the median time of 60.0 minutes (mean, 102.8 minutes) in 2008. Of patients with acute ischemic stroke, 7.9% were treated with IV-TPA in 2010, an increase from the 4.6% in 2005. Particularly, IV-TPA use for eligible patients substantially increased, from 21.7% in 2005 to 74.0% in 2010. The proportion of hospitals equipped with a stroke unit has increased from 1.1% in 2005 to 19.4% in 2010. Performance, as measured by quality indicators, has steadily improved since 2005, and the performance rates for most indicators were greater than 90% in 2010 except for early rehabilitation consideration (89.4%) and IV-TPA use for eligible patients (74.0%). In summary, the current report indicates a substantial improvement in in-hospital acute stroke care, but also emphasizes the need for enhancing public awareness and integrating the prehospital EMS system into acute stroke management. This report would be a valuable resource for understanding the current status and implementing initiatives to further improve public awareness of stroke and acute stroke care in Korea.
[show abstract][hide abstract] ABSTRACT: We evaluated the effectiveness of the 2010-2011 seasonal influenza vaccine for preventing laboratory-confirmed influenza in a Korean population. A retrospective case-control study was conducted among patients who visited selected hospitals from September 2010 to May 2011. A total of 483 laboratory-confirmed influenza patients were included in the analysis as case subjects. For each case patient, two types of control patients were chosen at a ratio of 1:1:1 and 966 control subjects were selected. Vaccine effectiveness (VE) was defined as [100 × (1-odds ratio for influenza in vaccinated versus non-vaccinated persons)]. The VE of the 2010-2011 seasonal influenza vaccine was 49.5% to 45.8% for both influenza A and B, and 50.8% to 47.2% for influenza A, according to the control type. The age-specific adjusted VE was 50.8% to 46.5% among subjects aged 19-49 years and 58.7% to 63.3% among those aged 50-64 years, according to the control type. Statistically significant VE was not found among those aged ≥ 65 years or against influenza B. The 2010-2011 seasonal influenza vaccine was effective for preventing laboratory-confirmed influenza, especially for influenza A, in a Korean population. Evidence of the effectiveness of the influenza vaccine in older adults or against influenza B was not found.
Clinical and vaccine Immunology: CVI 04/2013; · 2.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Even though the medulla contains the baroreceptor regulatory centers, few studies have focused on the autonomic dysfunction of lateral medullary infarction (LMI). Therefore, cardiac parasympathetic and sympathetic functions were compared in LMI patients and age-matched controls. We prospectively recruited 25 LMI patients who had ipsilateral Horner's sign and cardiac autonomic function testing without a history of diabetes, cardiac disease, or previous stroke. Parasympathetic function tests included beat-to-beat heart rate variation during deep breathing, 30:15 heart rate ratio testing while standing, and the valsalva ratio. Sympathetic function tests included blood pressure during active standing and sustained handgrip. The composite autonomic score (CAS) was measured as a total of 10 points; parasympathetic dysfunction was designated as ≥3 points in the parasympathetic subscores and sympathetic dysfunction as ≥2 points in the sympathetic subscores. Multiple regression analysis was performed to predict parasympathetic or sympathetic dysfunction. The mean age and stroke risk factors of the study population were not significantly different between the LMI group (n = 25) and control group (n = 29). However, cardiac autonomic functions were significantly different in the groups: parasympathetic dysfunction (14 vs. 4 patients, p = 0.011) and sympathetic dysfunction (3 vs. 13 patients, p = 0.008). In univariate analysis, male-gender (p = 0.011), right-side involvement (p = 0.035) and ventral involvement (p = 0.007) were significantly associated with parasympathetic dysfunction (CAS subscore ≥3). In multivariable analysis, the ventral involvement remained to be the independent predictor for parasympathetic dysfunction (OR 16.0; 95 % CI 2.2-118.3, p = 0.007). This study suggests that LMI patients are susceptible to cardiac parasympathetic dysfunction, especially in the ventral medulla.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Even though clopidogrel is the most used drug for cardiovascular prevention, resistance occurs in significant numbers. Therefore, we evaluated platelet aggregation ability of thienopyridines in relation with various genotypes. METHOD: The study population was randomly assigned with clopidogrel (n=43), ticlopidine (n=41), or ticlopidine plus Gingko Biloba extract (EGb) (n=43). Dosage was maintained as 75mg clopidogrel daily, 250mg ticlopidine twice daily, and 250mg ticlopidine plus 80mg Gingko Biloba extract twice daily. Using multiple electrodes aggregometry, platelet aggregation was measured by activators of adenosine diphosphate (ADP), arachidonic acid (ASP), and thrombin (TRAP) at baseline (T0), 7days (T1), and 90days (T2). Side-effects were analyzed in the 3 groups. Inhibition of platelet aggregation (IPA) was defined as percent decrease at T0 and T1. Non-responsiveness (<IPA 20%) was analyzed according to cytochrome P450 polymorphisms. RESULTS: There was no difference of general demographics and platelet aggregation at baseline in all groups. A significant difference of platelet aggregation showed on ADP test in the groups at T1 (28.9±17.2 vs.22.7±11.1 vs. 14.6±10.3%, p<0.001) and T2 (27.5±24.5 vs.18.3±16.6 vs. 14.4±9.8%, p=0.007), whereas ASP (p=0.064) and TRAP tests (p=0.143) had no differences at T1. Serious adverse events had no differences among the groups (p=0.902). CYP2C19 *2 alleles had poor responsiveness of clopidogrel (p=0.038), and not in ticlopidine (p=0.780). CONCLUSIONS: This finding suggests that ticlopidine plus Gingko Biloba extract has sufficient anti-platelet abilities with an acceptable profile of adverse events and CYP2C19 *2 alleles are associated with clopidogrel responsiveness.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Mechanical thrombectomy devices have recently been developed and approved for recanalization of intracranial arterial occlusion. Here, we investigated the feasibility of combined stent-assisted and clot aspiration mechanical thrombectomy for effective recanalization of acute carotid terminus occlusion (CTO). METHODS: Ten consecutive patients with acute ischemic stroke secondary to CTO who underwent intra-arterial (IA) treatment with both stent retrieval and negative-pressured clot aspiration systems were enrolled. Periprocedural and radiologic findings and clinical outcomes were evaluated. RESULTS: The median age was 69 years (range, 47-86 years), and the median initial NIHSS score was 17.5 (range, 12-33). Mechanical thrombectomy was performed using a combination of the Solitaire stents and Penumbra system. Thrombolysis in cerebral ischemia [TICI] grade II-III was achieved in eight patients (80.0 %); complete recanalization of the CTO (TICI III) was achieved in three of those patients. Any type of intracranial hemorrhages occurred in four patients (40.0 %), but parenchymal hematoma type 2 was not observed. Four patients died within 3 months (40.0 %). CONCLUSIONS: Combined mechanical thrombectomy treatment was effective for recanalization of acute CTO. The combination of Solitaire and Penumbra devices can be considered as a treatment option for CTO.
[show abstract][hide abstract] ABSTRACT: INTRODUCTION:: Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non-small-cell lung cancer. METHODS:: Medical records of 105 patients were retrieved and retrospectively analyzed to find the prognostic factors of patients' survival and symptom responses, including intracranial pressure (ICP) control. RESULTS:: There were 44 men and 61 women, with a median age of 56 years (range, 31-75 years). Patients received a median five rounds of intraventricular chemotherapy (range, 1-49 rounds). The most common presenting symptom was headache (77%) with nausea or vomiting, which showed the highest response rate of 42%. Altered mentality (36%), cranial neuropathy (15%), and cauda equina symptoms (12%) revealed 10% or less of symptom response. Only eight patients (7.6%) showed negative conversion of cerebrospinal fluid cytology. Median overall survival was 3.0 months (range, 0.5-21.5 months). Age (≥60 years), poor Karnofsky performance score (< 70), and uncontrolled ICP were found to be unfavorable prognostic factors for patient survival. A greater amount of intraventricular chemotherapy, which was evaluated as time-dependent covariate, and concurrent systemic chemotherapy significantly improved overall survival in the multivariable analysis. CONCLUSION:: Intraventricular chemotherapy for patients with LMC from non-small-cell lung cancer could palliate associated symptoms and prolong patients' survival. Careful selection of patients for intraventricular chemotherapy is recommended with aggressive ICP control and concurrent systemic chemotherapy.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2013; · 4.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The arising critical implications of Rho kinase signaling in cardiovascular diseases have been attracting attention in the pharmacological potential of Rho kinase inhibitors. We identified a novel inhibitor of Rho kinase (2-(1H-indazole-5-yl)amino-4-methoxy -6-piperazino triazine; DW 1865) and characterized its effects in biochemical, cellular, tissue and animal based assays. DW 1865 potently inhibited the kinase activity of both Rho kinase 1 and Rho kinase 2 in vitro, and behaved as an ATP-competitive inhibitor. Interestingly, DW1865 was 10 times more potent in inhibiting Rho kinase activities than fasudil as a selective Rho kinase inhibitor. The activity of DW1865 was shown to be highly selective for Rho kinase in the panel assay of 13 other kinases. In the isolated vascular tissue study, DW1865 exerted vasorelaxation in phenylephrine- or 5-hydroxytriptamine-induced contraction in a concentration-dependent manner manner. In spontaneously hypertensive rats, administration of DW1865 caused a significant and dose-related reduction in blood pressure. Furthermore, DW1865 blocked angiotensin II-induced stress fiber formation and cellular hypertrophy in rat heart-derived H9c2 cells. Taken together, these results suggest that DW1865 is a highly selective and potent Rho kinase inhibitor that will alleviate the pathophysiological actions of Rho kinase such as stress fiber formation, cellular hypertrophy, and hypertension.
European journal of pharmacology 01/2013; · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
In lung cancer patients with acquiring resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), an intra-patient heterogeneity in response to retreatment with EGFR-TKIs remains to be elucidated.
Patients and Methods
Sixty-eight patients with advanced non-small cell lung cancer who received second EGFR-TKIs after systemic progression following durable response to first EGFR-TKIs were retrospectively reviewed. All tumor lesions identified on radiological images before second EGFR-TKIs were categorized into organs. Tumor response to EGFR-TKIs was assessed per patient and per organ. Mixed response (MR) was defined as the coexistence of at least two responsive and progressive organs.
Tumor lesions were detected in 244 organs. The response rate (RR) and median time to progression (TTP) to second EGFR-TKIs for patients were 26.5% and 11.6 weeks (95% CI, 8.5–14.7 weeks) while the RR and median TTP for organs were 38.8% and 17.3 weeks (95% CI, 14.8–19.8 weeks). Of 35 patients categorized to progressive disease, 22 (62.8%) showed MR. Among organs, the RR was highest for central nervous system (CNS) but lowest for liver (CNS vs. others vs. liver; 77.8%, 36.9%, 17.6%; P< 0.001). Multivariate analysis confirmed the organ type and prior drug sensitivity at the time of stopping first EGFR-TKIs as predictors for the risk of progression to second EGFR-TKIs in organs.
The intra-patient heterogeneity in response to second EGFR-TKIs is not a rare event. The organ type and prior drug sensitivity at the failure time of first EGFR-TKIs may predict the efficacy to second EGFR-TKIs in individual organs.
Clinical Lung Cancer 01/2013; · 2.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the Part I of Stroke Statistics in Korea is to summarize nationally representative data of the epidemiology and risk factors of stroke in a single document. Every year, approximately 105,000 people experience a new or recurrent stroke and more than 26,000 die of stroke, which indicates that every 5 minutes stroke attacks someone and every 20 minutes stroke kills someone in Korea. Stroke accounts for roughly 1 of every 10 deaths. The estimated stroke prevalence is about 795,000 in people aged ≥30 years. The nationwide total cost for stroke care was 3,737 billion Korean won (US$3.3 billion) in 2005. Fortunately, the annual stroke mortality rate decreased substantially by 28.3% during the first decade of the 21th century (53.2/100,000 in 2010). Among OECD countries, Korea had the lowest in-hospital 30-day case-fatality rate for ischemic stroke and ranked third lowest for hemorrhagic stroke in 2009. The proportion of ischemic stroke has steadily increased and accounted for 76% of all strokes in 2009. According to hospital registry studies, the 90-day mortality rate was 3-7% for ischemic stroke and 17% for intracerebral hemorrhage. For risk factors, among Korean adults ≥30 years of age, one in 3-4 has hypertension, one in 10 diabetes, and one in 7 hypercholesterolemia. One in 3 Korean adults ≥19 years of age is obese. Over the last 10 years, the prevalence of hypertension slightly decreased, but the prevalence of diabetes, hypercholesterolemia, and obesity increased. Smoking prevalence in men has decreased, but is still as high as 48%. This report could be a valuable resource for establishing health care policy and guiding future research directions.
[show abstract][hide abstract] ABSTRACT: Lung cancer is the leading cause of cancer deaths in Korea. The objective of the present study was to develop an individualized risk prediction model for lung cancer in Korean men using population-based cohort data.
From a population-based cohort study of 1,324,804 Korean men free of cancer at baseline, the individualized absolute risk of developing lung cancer was estimated using the Cox proportional hazards model. We checked the validity of the model using C statistics and the Hosmer-Lemeshow chi-square test on an external validation dataset.
The risk prediction model for lung cancer in Korean men included smoking exposure, age at smoking initiation, body mass index, physical activity, and fasting glucose levels. The model showed excellent performance (C statistic = 0.871, 95% CI = 0.867-0.876). Smoking was significantly associated with the risk of lung cancer in Korean men, with a four-fold increased risk in current smokers consuming more than one pack a day relative to non-smokers. Age at smoking initiation was also a significant predictor for developing lung cancer; a younger age at initiation was associated with a higher risk of developing lung cancer.
This is the first study to provide an individualized risk prediction model for lung cancer in an Asian population with very good model performance. In addition to current smoking status, earlier exposure to smoking was a very important factor for developing lung cancer. Since most of the risk factors are modifiable, this model can be used to identify those who are at a higher risk and who can subsequently modify their lifestyle choices to lower their risk of lung cancer.
PLoS ONE 01/2013; 8(2):e54823. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pathway-based analysis, used in conjunction with genome-wide association study (GWAS) techniques, is a powerful tool to detect subtle but systematic patterns in genome that can help elucidate complex diseases, like cancers. Here, we stepped back from genetic polymorphisms at a single locus and examined how multiple association signals can be orchestrated to find pathways related to lung cancer susceptibility. We used single-nucleotide polymorphism (SNP) array data from 869 non-small cell lung cancer (NSCLC) cases from a previous GWAS at the National Cancer Center and 1,533 controls from the Korean Association Resource project for the pathway-based analysis. After mapping single-nucleotide polymorphisms to genes, considering their coding region and regulatory elements (±20 kbp), multivariate logistic regression of additive and dominant genetic models were fitted against disease status, with adjustments for age, gender, and smoking status. Pathway statistics were evaluated using Gene Set Enrichment Analysis (GSEA) and Adaptive Rank Truncated Product (ARTP) methods. Among 880 pathways, 11 showed relatively significant statistics compared to our positive controls (PGSEA≤0.025, false discovery rate≤0.25). Candidate pathways were validated using the ARTP method and similarities between pathways were computed against each other. The top-ranked pathways were ABC Transporters (PGSEA<0.001, PARTP = 0.001), VEGF Signaling Pathway (PGSEA<0.001, PARTP = 0.008), G1/S Check Point (PGSEA = 0.004, PARTP = 0.013), and NRAGE Signals Death through JNK (PGSEA = 0.006, PARTP = 0.001). Our results demonstrate that pathway analysis can shed light on post-GWAS research and help identify potential targets for cancer susceptibility.
PLoS ONE 01/2013; 8(6):e65396. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: During the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B. METHODOLOGYPRINCIPAL FINDINGS: We analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05). CONCLUSIONS: The proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.
PLoS ONE 01/2013; 8(5):e62685. · 3.73 Impact Factor