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Background: This study was performed to investigate the disease burden of seasonal influenza in adults ≥20 years of age in Korea, based on surveillance data from the Hospital-based Influenza Morbidity & Mortality Surveillance (HIMM) network. Materials and methods: The HIMM network is composed of two surveillance systems: emergency room-based and inpatients-based surveillance. A total of ten university hospitals all over the country are included in the surveillance network. The adult catchment population of the HIMM network was calculated by using the data of each hospital and the database of the Health Insurance Review and Assessment Service (HIRA) of Korea. The incidence rates of laboratory-confirmed medically-attended influenza, laboratory-confirmed influenza-related admission and laboratory-confirmed influenza-related death were calculated based on the catchment population. The socioeconomic burden of influenza was estimated using the human capital approach. Results: During the 2013–2014 influenza season, the calculated adult catchment population of the HIMM network was 1,380,000. The incidence of medically-attended laboratory-confirmed influenza infection was 242.8 per 100,000 adults. The incidence of laboratory-confirmed influenza-related admission was 57.9 per 100,000 adults. The incidence of laboratory-confirmed influenza-related death was 3.1 per 100,000 adults. The total socioeconomic cost of 2013–2014 seasonal influenza in Korean adult population was estimated as 125 million USD (1 USD = 1,100 KRW). Conclusion: The disease burden of 2013–2014 seasonal influenza in Korean adult population is very high and indicates that more active prevention and control policies will be needed to decrease the burden. Additional researches will be needed to assess the burden of seasonal influenza in the Korean child population. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of the 2011–2012 seasonal influenza vaccine was evaluated in adult Korean populations with regard to how well it could prevent laboratory-confirmed influenza and influenza-related complications. Materials and Methods: A retrospective case-control and retrospective cohort study was conducted among patients who visited four selected hospitals from September 2011 to May 2012. The analysis included 1,130 laboratory-confirmed influenza patients. For each influenza case, one control patient was chosen at a ratio of 1:1. A control was defined as an age group-matched patient who visited the same hospital with influenza-like illness within 48 hours of symptom onset but for whom laboratory tests were negative for influenza. Age group and visit date were matched between the cases and controls. Vaccine effectiveness (VE) was defined as [100 × (1-odds ratio for influenza in vaccinated versus non-vaccinated persons)]. The patients with laboratory-confirmed influenza were followed for at least one month through reviewing the medical records and conducting a telephone interview. Results: The VE of the 2011–2012 seasonal influenza vaccine was 3.8% [95% confidence interval (CI), -16.5% to 20.6%] for preventing laboratory-confirmed influenza, -16.1% (95% CI, -48.3 to 9.1) for influenza A and 26.2% (95% CI, -2.6 to 46.2) for influenza B. The age-specific adjusted VE was 0.3% (95% CI, -29.4 to 23.1) among participants aged 19 to 49 years, 11.9% (95% CI, -34.3 to 42.2) among those aged 50 to 64 years and -3.9% (-60.1 to 32.5) among those aged ≥65 years. The adjusted VE for preventing any influenza-related complications was -10.7% (95% CI, -41.1% to 42.2%). Conclusions: The 2011–2012 seasonal influenza vaccine was not effective in preventing laboratory-confirmed influenza or influenza-related complications in adult Korean populations. [ABSTRACT FROM AUTHOR]

How extracellular molecules influence the direction of axon guidance is poorly understood. The HSN axon of Caenorhabditis elegans is guided towards a ventral source of secreted UNC-6 (netrin). The axon’s outgrowth response to UNC-6 is mediated by the UNC-40 (DCC) receptor. We have proposed that in response to the UNC-6 molecule the direction of UNC-40-mediated axon outgrowth is stochastically determined. The direction of guidance is controlled by asymmetric cues, including the gradient of UNC-6, that regulate the probability that UNC-40-mediated axon outgrowth is directed on average, over time, in a specific direction. Here we provide genetic evidence that a specialized extracellular matrix, which lies ventral to the HSN cell body, regulates the probability that UNC-40-mediated axon outgrowth will be directed ventrally towards the matrix. We show that mutations that disrupt the function of proteins associated with this matrix, UNC-52 (perlecan), UNC-112 (kindlin), VAB-19 (Kank), and UNC-97 (PINCH), decrease the probability of UNC-40-mediated axon outgrowth in the ventral direction, while increasing the probability of outgrowth in the anterior and posterior directions. Other results suggest that INA-1 (α integrin) and MIG-15 (NIK kinase) signaling mediate the response in HSN. Although the AVM axon also migrates through this matrix, the mutations have little effect on the direction of AVM axon outgrowth, indicating that responses to the matrix are cell-specific. Together, these results suggest that an extracellular matrix can regulate the direction of UNC-6 guidance by increasing the probability that UNC-40-mediated axon outgrowth activity will be oriented in a specific direction. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is a leading infectious cause of morbidity and mortality among adults. Pneumococcal pneumonia (PP) is the most common vaccine-preventable bacterial etiology of pneumonia. In this study, we estimated the incidence of community-acquired pneumonia (CAP) and pneumococcal diseases among Korean adults. Methods: Clinical and microbiological databases from three hospitals were retrospectively reviewed to determine the incidence and case fatality rates of CAP and pneumococcal diseases in Korean adults aged ≥19 years from 2011 to 2014. Incidence and case fatality rates of CAP, PP and invasive pneumococcal diseases (IPD) were evaluated based on the catchment population. Catchment population was calculated using national health insurance data, estimating the proportion of patients with pneumonia that were medically attended at each hospital. Results: Among 5,783 patients with medically attended CAP, 833 (14.4%) had PP. For IPD, a total of 91 culture-confirmed cases were identified. The overall incidence of CAP was 307.7 cases per 100,000 persons per year with an in-hospital mortality rate of 6.2%. The estimated annual incidence of pneumococcal pneumonia was 42.2–49.4 cases per 100,000 persons per year, increasing with age to >280 per 100,000 persons per year in older patients over 70 years. The annual incidence of IPD had a range of 4.1–6.5 cases per 100,000 persons per year. The overall case fatality rate for invasive pneumococcal diseases was 30.8% with the highest rate of 66.7% in patients over 80 years. Conclusion: Over the study period, incidences of CAP, PP and IPD were consistently high, particularly in older people. These results provide baseline data to establish healthcare strategies and estimate their impact among Korean adults. [ABSTRACT FROM AUTHOR]

To evaluate the frequency and appropriateness of indwelling urinary catheters (IUC) use and the incidence of catheter-associated urinary tract infections (CA-UTI), and explore the risk factors for CA-UTI in hospitals as a whole, we conducted a study. This study was divided into two parts; a point-prevalence study on Dec 12th 2012 and a prospective cohort study from Dec 13th 2012 to Jan 9th 2013 were performed in six hospitals in Korea. All hospitalized patients with newly-placed IUCs were enrolled and monitored weekly for 28 days after IUC placement. In the point-prevalence study, the IUCs were present in median 14.9/100 hospitalized patients (1Q 14, 3Q 16) across the six hospitals. In the prospective cohort study, the median IUC-days per patient was 5 (1Q 3, 3Q 10) and the median CA-UTI prevalence per 1,000 catheter days was 1.9 (1Q 0.7, 3Q 3.8) with significant inter-hospital variation. The proportion of patients with inappropriate IUC maintenance increased with number of IUC-days (8.5% on day 7, 9.4% on day 14, 16.3% on day 21, and 23.1% on day 28). Urinary output monitoring (23/36, 63.9%) was the most common indication for inappropriate use after 1 week of ICU placement. In multivariate analysis, IUC-days was significantly associated with the development of CA-UTI (odds ratio 1.122, 95% confidence interval 1.074–1.173, P< 0.001). IUC-days and CA-UTI rates vary between hospitals. IUC-days is a risk factor for CA-UTI, and is correlated with inappropriate use. [ABSTRACT FROM AUTHOR]

Background: Although the 13-valent pneumococcal conjugate vaccine (PCV13) showed good efficacy against pneumococcal disease in the the CAPiTA trial, the 23-valent pneumococcal polysaccharide vaccination (PPSV23) program has been ongoing for older adults aged ≥ 65 years in Korea since May of 2013. This study aimed to evaluate the cost-effectiveness of the current vaccination strategy (a single-dose PPSV23 vaccination) compared to a single-dose PCV13 vaccination and sequential PCV13-PPSV23 vaccinations in the elderly population aged ≥ 65 years. Methods: Using a Markov model, the incremental cost-effectiveness ratios (ICERs) of three vaccination strategies were assessed in a societal context. The transition probabilities, utility weights to estimate quality adjusted life year (QALY), and disease treatment costs were either calculated or cited from published data and the Health Insurance Review and Assessment Service. Simulations were performed in hypothetical cohorts of Korean adults aged ≥ 19 years. The vaccine effectiveness of PPSV23 was cited from a Cochrane Review report, while PCV13 effectiveness data were gathered from the CAPiTA trial. Results: Current PPSV23 vaccination strategies were cost-effective (ICER, $25,786 per QALY). However, the administration of PCV13 as a substitute for PPSV23 was shown to be more cost-effective than PPSV23 vaccination (ICER, $797 per QALY). Sequential PCV13-PPSV23 vaccination was also more cost-effective than PPSV23 for elderly people aged ≥ 65 years. In sensitivity analysis assuming significant PPSV23 effectiveness (50%) against non-bacteremic pneumococcal pneumonia, the PCV13 vaccination strategy was superior to the PPSV23 vaccination strategy in terms of cost-effectiveness. Conclusion: The results suggest that PCV13 vaccination is more cost-effective in elderly subjects aged ≥ 65 years compared to the current PPSV23 vaccination strategy. When complete data is obtained in 2018 on the maximal herd effects of childhood PCV13 immunization, the incidence of pneumococcal pneumonia and the cost-effectiveness of vaccination strategies need to be reassessed. [ABSTRACT FROM AUTHOR]

A neuroprotective role of autophagy mediates the degradation of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). The previous study showed cilostazol modulates autophagy by increasing beclin1, Atg5 and LC3-II expressions, and depletes intracellular Aβ accumulation. This study elucidated the mechanisms through which cilostazol modulates the autophagic degradation of Aβ in neurons. In N2a cells, cilostazol (10–30 μM), significantly increased the expression of P-AMPKα (Thr 172) and downstream P-ACC (acetyl-CoA carboxylase) (Ser 79) as did resveratrol (SIRT1 activator), or AICAR (AMPK activator), which were blocked by KT5720, compound C (AMPK inhibitor), or sirtinol. Furthermore, phosphorylated-mTOR (Ser 2448) and phosphorylated-P70S6K (Thr 389) expressions were suppressed, and LC3-II levels were elevated in association with decreased P62/Sqstm1 by cilostazol. Cilostazol increased cathepsin B activity and decreased p62/SQSTM 1, consequently decreased accumulation of Aβ1–42 in the activated N2aSwe cells, and these results were blocked by sirtinol, compound C and bafilomycin A1 (autophagosome blocker), suggesting enhanced autophagosome formation by cilostazol. In SIRT1 gene-silenced N2a cells, cilostazol failed to increase the expressions of P-LKB1 (Ser 428) and P-AMPKα, which contrasted with its effect in negative control cells transfected with scrambled siRNA duplex. Further, N2a cells transfected with expression vectors encoding pcDNA SIRT1 showed increased P-AMPKα expression, which mimicked the effect of cilostazol in N2a cells; suggesting cilostazol-stimulated expressions of P-LKB1 and P-AMPKα were SIRT1-dependent. Unlike their effects in N2a cells, in HeLa cells, which lack LKB1, cilostazol and resveratrol did not elevate SIRT1 or P-AMPKα expression, indicating cilostazol and resveratrol-stimulated expressions of SIRT1 and P-AMPKα are LKB1-dependent. In conclusion, cilostazol upregulates autophagy by activating SIRT1-coupled P-LKB1/P-AMPKα and inhibiting mTOR activation, thereby decreasing Aβ accumulation. [ABSTRACT FROM AUTHOR]

Background: Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. Methods: We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. Results: Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B) = 1.72, 95% CI = 1.12–2.63, p = 0.013) and sodium bicarbonate administration (Exp (B) = 6.27, 95% CI = 1.10–35.78, p = 0.039). Conclusions: Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality. [ABSTRACT FROM AUTHOR]

Background: Watson for oncology (WFO) is a cognitive computing system providing decision support. We evaluated the concordance rates between the treatment options determined by WFO and those determined by a multidisciplinary team (MDT). Methods: We reviewed the medical charts of patients diagnosed with colorectal cancer who visited the MDT at a single tertiary medical center from November 2016 to April 2017. WFO classified the treatment options for specific patients into three categories: ‘Recommended’, ‘For consideration’, and ‘Not recommended’. Concordance rates between the WFO- and MDT-determined chemotherapy options, and the factors that potentially influence the concordance rate, were analyzed. Results: Sixty-nine patients with colorectal cancer met with the MDT from Nov. 2016 to Feb. 2017. The mean age of the patients was 62 years (range: 34–86 years), and more patients were male (47/69) than female. Of the 69 patients, 51 (73.9%) were diagnosed with colon cancer, of whom 46.4% received the same regimen recommendation from WFO (‘Recommended’) as they did from the MDT. After inclusion of the ‘For consideration’ category from WFO, the concordance rate increased to 87.0%. The concordance rate between MDT and NCCN guidelines was 97.1%, and that between the WFO and NCCN guidelines was 88.4%. The concordance rates between WFO and MDT were significantly lower in patients with stage II, IIIC, or IV disease (P<0.001), and the colorectal cancer stage was the only statistically significant factor discriminating between WFO and MDT. Conclusions: The concordance rate between chemotherapy regimens for colorectal cancer determined by MDT versus WFO recommendations was 46.4%. After including the ‘For consideration’ category from WFO, the concordance rate increased to 88.4%. Further modification and improvement of the WFO prioritizing algorithm used to recommend treatment may increase the usefulness of WFO in the clinic. [ABSTRACT FROM AUTHOR]

Background: Influenza and pneumonia are leading causes of morbidity and mortality among the elderly. Although vaccination is a main strategy to prevent these infectious diseases, concerns remain with respect to vaccine effectiveness. Methods: During three influenza seasons (2014–2015, 2015–2016 and 2016–2017), we evaluated the effectiveness of the influenza and pneumococcal vaccines against pneumonia and acute exacerbation of cardiopulmonary diseases among the elderly aged ≥65 years with influenza-like illness (ILI). Demographic and clinical data were collected prospectively. Results: Among 2,119 enrolled cases, 1,302 (61.4%) and 871 (41.1%) received the influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPV23), respectively. During an A/H3N2-dominant season with poor influenza vaccine effectiveness (2014–2015 season), neither the influenza vaccine nor PPV23 showed significant effectiveness against pneumonia or acute exacerbation of cardiopulmonary diseases. During seasons with good influenza vaccine effectiveness (2015–2016 and 2016–2017 seasons), the influenza vaccine was effective in preventing pneumonia, but PPV23 was not. In particular, the influenza vaccine was effective in preventing acute exacerbation of heart diseases (75.0%) during the A/H1N1-dominant 2015–2016 season. Conclusion: The influenza vaccine was effective in preventing pneumonia only during vaccine-matched seasons with good effectiveness against circulating influenza viruses. In addition, the influenza vaccine was cardio-protective during a vaccine-matched A/H1N1-dominant season. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend a break-in period of 2 weeks before starting peritoneal dialysis (PD), but PD within 14 days is also an acceptable and safe alternative to hemodialysis (HD) in patients with an urgent need. However, the effect of the break-in period within 48 hours or later had not been evaluated for early technical complications, long-term maintenance, and survival in patients starting urgent PD. Methods: Of 360 patients with a surgically inserted PD catheter, we evaluated 190 patients who needed urgent PD and 29 patients who received conventional PD at a single center between January 2007 and December 2014 in this retrospective observational study. Enrolled patients were divided according to break-in period of <48 hours (P1) or 2–13 days (P2) before starting urgent PD. The primary endpoint was incidence of early technical complications and secondary endpoints included long-term PD maintenance, and patient survival. Results: PD was started in 103 patients (54.2%) within 48 hours and in 87 patients (45.8%) within 2 to 13 days. The incidence of early technical complication was significantly higher in P1 group (28.2%) than in P2 group (10.3%) (P = 0.002). The need for a repositioning procedure was significantly greater in P1 group (14.6%) than in P2 group (3.4%) (P = 0.009). However, we observed no significant differences between the two groups with respect to the prevalence of catheter dysfunction requiring change to HD within 6 months or incidence of peritonitis or exit-site infection. There was no significant difference in PD maintenance and patient survival according to the break-in period between P1 and P2 as well as against the control group. Conclusion: Urgent PD was associated with a low incidence of early technical complications if start was avoided within 48 hours after catheter insertion, and long-term PD maintenance was independent of the break-in period. [ABSTRACT FROM AUTHOR]

In the 2016–2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19–64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016–2017 influenza season. [ABSTRACT FROM AUTHOR]

Introduction: Initial lactate level, lactate clearance, C-reactive protein, and procalcitonin in critically ill patients with sepsis are associated with hospital mortality. However, no study has yet discovered which factor is most important for mortality in severe sepsis patients with lactic acidosis. We sought to clarify this issue in patients with lactic acidosis who were supplementing with sodium bicarbonate. Materials and Methods: Data were collected from a single center between May 2011 and April 2014. One hundred nine patients with severe sepsis and lactic acidosis who were supplementing with sodium bicarbonate were included. Results: The 7-day mortality rate was 71.6%. The survivors had higher albumin levels and lower SOFA, APACHE II scores, vasopressor use, and follow-up lactate levels at an elapsed time after their initial lactate levels were checked. In particular, a decrement in lactate clearance of at least 10% for the first 6 hours, 24 hours, and 48 hours of treatment was more dominant among survivors than non-survivors. Although the patients who were treated with broad-spectrum antibiotics showed higher illness severity than those who received conventional antibiotics, there was no significant mortality difference. 6-hour, 24-hour, and 48-hour lactate clearance (HR: 4.000, 95% CI: 1.309–12.219, P = 0.015) and vasopressor use (HR: 4.156, 95% CI: 1.461–11.824, P = 0.008) were significantly associated with mortality after adjusting for confounding variables. Conclusions: Lactate clearance at a discrete time point seems to be a more reliable prognostic index than initial lactate value in severe sepsis patients with lactic acidosis who were supplementing with sodium bicarbonate. Careful consideration of vasopressor use and the initial application of broad-spectrum antibiotics within the first 48 hours may be helpful for improving survival, and further study is warranted. [ABSTRACT FROM AUTHOR]

Autophagy is a vital pathway for the removal of β-amyloid peptide (Aβ) and the aggregated proteins that cause Alzheimer’s disease (AD). We previously found that cilostazol induced SIRT1 expression and its activity in neuronal cells, and thus, we hypothesized that cilostazol might stimulate clearances of Aβ and C-terminal APP fragment β subunit (APP-CTFβ) by up-regulating autophagy.When N2a cells were exposed to soluble Aβ1–42, protein levels of beclin-1, autophagy-related protein5 (Atg5), and SIRT1 decreased significantly. Pretreatment with cilostazol (10–30 μM) or resveratrol (20 μM) prevented these Aβ1–42 evoked suppressions. LC3-II (a marker of mammalian autophagy) levels were significantly increased by cilostazol, and this increase was reduced by 3-methyladenine. To evoke endogenous Aβ overproduction, N2aSwe cells (N2a cells stably expressing human APP containing the Swedish mutation) were cultured in medium with or without tetracycline (Tet+ for 48 h and then placed in Tet- condition). Aβ and APP-CTFβ expressions were increased after 12~24 h in Tet- condition, and these increased expressions were significantly reduced by pretreating cilostazol. Cilostazol-induced reductions in the expressions of Aβ and APP-CTFβ were blocked by bafilomycin A1 (a blocker of autophagosome to lysosome fusion). After knockdown of the SIRT1 gene (to ~40% in SIRT1 protein), cilostazol failed to elevate the expressions of beclin-1, Atg5, and LC3-II, indicating that cilostazol increases these expressions by up-regulating SIRT1. Further, decreased cell viability induced by Aβ was prevented by cilostazol, and this inhibition was reversed by 3-methyladenine, indicating that the protective effect of cilostazol against Aβ induced neurotoxicity is, in part, ascribable to the induction of autophagy. In conclusion, cilostazol modulates autophagy by increasing the activation of SIRT1, and thereby enhances Aβ clearance and increases cell viability. [ABSTRACT FROM AUTHOR]

High mobility group box chromosomal protein 1 (HMGB-1) released from injured cells plays an important role in the development of arthritis. This study investigated the anti-angiogenic effects of cilostazol in collagen-induced arthritis (CIA) of mice, and the underlying mechanisms involved. The expressions of HIF-1α, VEGF, NF-κB p65 and SIRT1 in synovial fibroblasts obtained from rheumatoid arthritis (RA) patients were assessed by Western blotting, and in vitro and in vivo angiogenesis were analyzed. Tube formations by human microvascular endothelial cells (HMVECs) were significantly increased by direct exposure to HMGB1 or to conditioned medium derived from HMGB1-stimulated RA fibroblasts, and these increases were attenuated by cilostazol, the latter of which was blocked by sirtinol. HMGB1 increased the expression of HIF-1α and VEGF and concomitantly increased nuclear NF-κB p65 and DNA binding activity, but these effects of HMGB1 were inhibited by cilostazol. SIRT1 protein expression was time-dependently decreased (3–24 hr) by HMGB1, which was recovered by pretreatment with cilostazol (1–30 µM) or resveratrol, accompanying with increased SIRT1 deacetylase activity. In the tibiotarsal joint tissues of CIA mice treated with vehicle, HIF-1α- and VEGF-positive spots and CD31 staining were markedly exaggerated, whereas SIRT1 immunofluorescence was diminished. These variables were wholly reversed in cilostazol (30 mg/kg/day)-treated mice. Furthermore, number of blood vessels stained by von Willebrand factor antibody was significantly lower in cilostazol-treated CIA mice. Summarizing, cilostazol activated SIRT1 and inhibited NF-κB-mediated transcription, thereby suppressing the expression of HIF-1α and VEGF. In addition, cilostazol caused HIF-1α deacetylation by enhancing SIRT1 activity and reduced VEGF production, thereby had an anti-angiogenic effect in vitro studies and in CIA murine model. [ABSTRACT FROM AUTHOR]

Approximately 50% of patients with primary colorectal carcinoma develop liver metastases. Understanding the genetic differences between primary colon cancer and their metastases to the liver is essential for devising a better therapeutic approach for this disease. We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis. We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss. The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar somatic copy number alteration patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number alterations. Our results suggest that about half of the metastatic colorectal carcinoma had the same clonal origin with their primary colorectal carcinomas, whereas remaining cases were genetically distinct from their primary carcinomas. These findings underscore the need to evaluate metastatic lesions separately for optimized therapy, rather than to extrapolate from primary tumor data. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: A well-constructed and properly operating influenza surveillance scheme is essential for public health. This study was conducted to evaluate the distribution of respiratory viruses in patients with influenza-like illness (ILI) through the first teaching hospital-based surveillance scheme for ILI in South Korea. Methods: Respiratory specimens were obtained from adult patients (≥18 years) who visited the emergency department (ED) with ILI from week 40, 2011 to week 22, 2012. Multiplex PCR was performed to detect respiratory viruses: influenza virus, adenovirus, coronavirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, parainfluenza virus, bocavirus, and enterovirus. Results: Among 1,983 patients who visited the ED with ILI, 811 (40.9%) were male. The median age of patients was 43 years. Influenza vaccination rate was 21.7% (430/1,983) during the 2011–2012 season. At least one comorbidity was found in 18% of patients. The positive rate of respiratory viruses was 52.1% (1,033/1,983) and the total number of detected viruses was 1,100. Influenza A virus was the dominant agent (677, 61.5%) in all age groups. The prevalence of human metapneumovirus was higher in patients more than 50 years old, while adenovirus was detected only in younger adults. In 58 (5.6%) cases, two or more respiratory viruses were detected. The co-incidence case was identified more frequently in patients with hematologic malignancy or organ transplantation recipients, however it was not related to clinical outcomes. Conclusion: This study is valuable as the first extensive laboratory surveillance of the epidemiology of respiratory viruses in ILI patients through a teaching hospital-based influenza surveillance system in South Korea. [ABSTRACT FROM AUTHOR]

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. Methodology/Principal 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. [ABSTRACT FROM AUTHOR]