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Background Incremental peritoneal dialysis (iPD) can be useful in patients with residual renal function (RRF). RRF was well preserved and similar survival was shown in iPD compared to conventional PD (cPD) in previous study. However, the long-term survival of iPD remains unclear compared to cPD in diabetic patients. This study evaluated whether patient survival, hospitalization and peritonitis, and PD survival in iPD were lower than cPD or not. Methods We conducted a 12-year retrospective observational study of 303 PD patients (232 cPD and 71 iPD) using propensity score matching by age, gender, and diabetes mellitus (DM). Finally, 78 cPD patients and 39 iPD patients were included and 44 patients had DM. Incremental PD was defined as starting PD with two or three manual exchanges per day. Results The median duration of iPD was 24.1 months and iPD had higher RRF than cPD. Compared to cPD, the patient survival, PD survival and hospitalization benefits were not found in iPD but diabetic iPD patients had significantly longer survival and less hospitalization. Cumulative risk for peritonitis was lower iPD and PD duration of iPD was longer than those of cPD. The iPD was an independent factor associated with survival in patients with DM. Conclusions Incremental PD may be a safe PD modality to initiate and maintain PD in less uremic patients with tolerable RRF. Incremental PD would be a benefit for survival in diabetic patients. Further prospective studies are necessary to confirm the effectiveness of iPD in PD patients with similar RRF.

Rationale: Emphysematous pancreatitis, a rare complication of acute necrotizing pancreatitis with a high mortality rate, is associated with gas-forming bacteria. When using the step-up approach for treating emphysematous pancreatitis, it is preferable to delay drainage interventions for 4 weeks. However, percutaneous drainage may be necessary, even in the early phase of acute pancreatitis, for a patient whose sepsis deteriorates despite optimal medical management. Percutaneous drainage can then be followed by endoscopic necrosectomy through the percutaneous tract. Patient concerns: A 52-year-old man was transferred to our hospital for treatment of sepsis and multiorgan failure associated with emphysematous pancreatitis. Diagnosis: An abdominal computed tomography scan had shown pancreatic and peripancreatic necrosis, along with extensive gas bubbles. Interventions: Despite optimal medical management, the patient's condition continued to deteriorate, and it became necessary to insert 2 percutaneous catheter drainages (PCDs), even though the patient was still in the early phase of pancreatitis. Each PCD was upsized and irrigated with sterile saline by an interventional radiologist twice a week. The infected necrosis around the tail of the pancreas was completely resolved after PCD. However, PCD through the transperitoneal route did not resolve necrosis around the pancreatic head. Following the PCDs, percutaneous pancreatic necrosectomy using an ultra-slim upper endoscope was performed, after which the patient recovered quickly and was discharged. Outcomes: Follow-up computed tomography was performed 12 weeks after the patient was discharged, and it showed complete resolution of the walled-off necrosis. The patient's condition improved without any fluid collection or complications. Lessons: PCD can be used in the early phase of emphysematous pancreatitis for patients who continue to deteriorate due to sepsis. This can easily be followed, if necessary, by percutaneous pancreatic necrosectomy using an ultra-slim endoscope.

Few studies have focused on clinical courses or viral loads in young asymptomatic or mild patients with COVID-19 infection. We sought to better understand the clinical course and association between viral load and prevalence of pneumonia in young COVID-19 patients with asymptomatic or mild disease severity. In this retrospective study, 106 COVID-19 young patients with asymptomatic or mild disease severity were analyzed for clinical characteristics, clinical course, prevalence of radiologically proven pneumonia and viral load. The cut-off value of viral load for presence of pneumonia was also investigated. The mean age was 28.0±9.3 years. Eleven patients (10.4%) experienced viral remission within one week of diagnosis, but one (0.9%) transferred to the hospital due to aggravation of pneumonia. Patients with pneumonia had significantly higher viral load than those without, and the cut-off value of the Ct value for presence of pneumonia were 31.38. The patients with pneumonia had significantly slower recovery times than those without. Diarrhea was significantly more common in patients with pneumonia than patients without pneumonia. In conclusion, most young asymptomatic and mildly symptomatic patients showed stable clinical course. There were significant differences in viral load and recovery times between patients with and without pneumonia.

Background: Neck pain is common musculoskeletal disorders in adult population. Acupuncture treatment has been widely used for treating neck pain. Nevertheless, previous systematic reviews (SRs) on acupuncture for neck pain remain controversial, and there is no SR for the comparative efficacy and safety of various types of acupuncture. Therefore, this study aims to evaluate and rank the effectiveness and safety of different types of acupuncture for neck pain by SR and network meta-analysis. Methods: Nine databases will be searched, including Ovid-MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure (CNKI), KoreaMed, Korean medical database (KMBASE), Korean Studies Information Service System (KISS), ScienceON, and Oriental Medicine Advanced Searching Integrated System (OASIS) from their inception to July 2021. The primary outcome is the change of pain intensity. A frequentist network meta-analysis will be performed to compare all relative outcomes of different acupuncture methods, using R software. The quality of included randomized controlled trials will be assessed by Cochrane Collaboration “risk of bias” tools and the evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation instrument. Results: The final findings of this network meta-analysis will be published in a recognized journal. Conclusions: Our study will evaluate and compare the effectiveness of various types of acupuncture for neck pain and provide clinicians with best option for what types of acupuncture treatments are effective. Trial registration number: INPLASY202120041

Background The massive outbreak of the novel coronavirus disease 2019 (COVID-19) in Daegu city and Gyeongsangbuk-do, Republic of Korea (ROK), caused the exponential increase in new cases exceeding 5000 within 6 weeks. Therefore, the community treatment center (CTC) with a digital health care monitoring system based on the smartphone application and personal health record platform (PHR) was implemented. Thus, we report our experience in one of the CTCs to investigate the role of CTC and the feasibility of the digital health care monitoring system in the COVID-19 pandemic. Methods The Gyeongbuk-Daegu 2 CTC was set up at the private residential facility. Admission criteria were 1) patients Results From Mar 3, 2020, to Mar 26, 2020, there was a total of 290 patients admitted to the facility. Males were 104 (35.9%). The median age was 37 years. The median time between the COVID-19 diagnosis and admission was 7 days. Five patients were identified and were transferred to the designed COVID-19 treatment hospital for their urgent medical needs. The smartphone application usage to report vital signs and symptoms was noted in 96% of the patients. There were no deaths of the patients. Conclusions Our results suggest that implementation of the CTC using a commercial residence facility and digital health care technology may offer valuable solutions to the challenges posed by the COVID-19 outbreak.

Background: Scoliosis is a spinal deformity and is diagnosed as Cobb angle being greater than 10°. Because it is accompanied with structural dysfunction, it can cause pain, worsen the patient's general health and quality of life. The prevalence of scoliosis has been increasing and many treatments, including surgical treatment and conservative treatment, such as observation, bracing, physiotherapy, and Chuna manual therapy (CMT), have been suggested. CMT is a manual therapy in Korean medicine that provides effective stimulation to the patient's body structure to treat structural dysfunction. After Korean national health insurance's coverage of CMT in 2019, the application of CMT for scoliosis has increased, and many studies have been reported. There have been attempts to elucidate the effectiveness of CMT on scoliosis; however, its effectiveness still remains unconfirmed. Therefore, the aim of this study is to evaluate the effectiveness and safety of CMT on scoliosis. Methods: The published randomized controlled trials that evaluated the effectiveness and safety of CMT for scoliosis will be searched for in multiple electronic databases without the limitation of country and language. Data on characteristics of studies, interventions, comparators, outcome measures, results, and information for assessment of study quality will be extracted. The primary outcome will be the Cobb angle and the secondary outcomes will be the scales of pain, function, quality of life and disability, and adverse events. Data synthesis and analysis will be conducted using the Review Manager software for Windows (RevMan ver. 5.3.; Copenhagen; The Nordic Cochrane Center, The Cochrane Collaboration, 2014). Subgroup analysis to identify the differences between different CMT maneuvers will also be performed. For risk of bias assessment, the “risk of bias” tool from Cochrane Collaboration will be used. Results: This study will present the clinical evidence on the effectiveness and safety of CMT on scoliosis. Conclusion: This study will propose useful evidence for treatment, further research, and health policies in the future.

Background: Kynurenine (Kyn) is a key inducer of an immunosuppressive tumor microenvironment (TME). Although indoleamine 2,3-dioxygenase (IDO)-selective inhibitors have been developed to suppress the Kyn pathway, the results were not satisfactory due to the presence of various opposing mechanisms. Here, we employed an orally administered novel Kyn pathway regulator to overcome the limitation of anti-tumor immune response.Methods: We identified a lead compound through the development of a deep learning model to predict compound-target interaction. Inhibitory activity of the lead compound against both IDO and tryptophan 2,3-dioxygenase (TDO) was evaluated using enzyme- and cell-based assays. CT26 colon cancer-bearing mice were treated with the lead compound and/or immune checkpoint inhibitors. Tumor samples were analyzed using histological, flow cytometry, and immune profiling assays.Results: We identified a novel core structure that inhibited both IDO and TDO. An orally available lead compound, STB-C017 (designated hereafter as STB), was then selected via validation of structural modification and in vitro assays. STB effectively inhibited the enzymatic and cellular activity of IDO and TDO in vitro. Moreover, it potently suppressed Kyn levels in both the plasma and tumor in vivo. The dose and schedule of STB administration were optimized based on the immunotherapeutic efficacy and toxicity. STB monotherapy increased the infiltration of CD8+ T cells into TME. In addition, it elicited an anti-cancer immune response with a strong activation of T cell immunity. STB reprogrammed the TME with widespread changes in immune-mediated gene signatures. Notably, STB-based combination immunotherapy elicited the most potent anti-tumor efficacy through concurrent treatment with immune checkpoint inhibitors (ɑPD-1 and/or ɑCTLA-4), leading to complete tumor regression and long-term overall survival.Conclusions: Our study demonstrated that a novel Kyn pathway regulator derived using deep learning technology can activate T cell immunity and potentiate immune checkpoint blockade by overcoming an immunosuppressive TME.

Background: Low back pain is a very common disease. Many patients with chronic low back pain (CLBP) have been treated by complementary and alternative medicine such as acupuncture (AT) treatment. A type of AT, thread embedding acupuncture (TEA), consists of a thread that can continually stimulate at the AT points and has mechanical and chemical effects. Although TEA was widely used in clinical practice, there was little evidence of its efficacy and safety for CLBP. Methods: This clinical trial was randomized, controlled, assessor-blinded, two-armed, parallel, and conducted in multiple centers. Four Korean medical institutions recruited 38 outpatients with CLBP. The participants were randomly allocated to a treatment group (TEA combined with AT) or a control group (only AT) in a 1:1 ratio. All participants received conventional AT twice a week for 8 weeks (16 sessions) at 15 AT points (GV3 and bilateral BL23, BL24, BL25, BL26, BL40, BL60, and EX-B5) and the treatment group participants additionally received TEA once a week for 8 weeks (8 sessions) on 10 AT points in the multifidus, spinal erector, and lumbar quadrate muscles. The primary outcome measure of this study was the change of visual analog scale (VAS) from baseline (0 week) to the end of intervention (8 weeks). Secondary outcome measures included clinically relevant improvement (minimal clinically important difference) and 3% to 50% decrease on VAS, disability level (Korean version of Roland and Morris disability questionnaire), quality of life (Korean version of European quality of life 5dimension), global assessment (patient global impression of change), economic analysis, credibility test, and safety assessment. Results: The treatment group showed a significant reduction in VAS scores when compared with the control group (–33.7 ± 25.1 vs –15.6 ± 17.0, P = .013). As for the secondary outcome measures, the treatment group showed significant difference in 50% decrease on VAS and patient global impression of change. There was no serious adverse event associated with TEA and AT. Conclusion: This clinical trial documents the efficacy and safety of TEA combined with AT for the management of CLBP.

Background: Scoliosis is a disease that affects all age groups and alters the three-dimensional deviation of the spinal axis. It is diagnosed when Cobb angle presents over 10 degrees and the reasons include aging, traumatic injuries, unknown origin, and disorders of congenital, neurological, musculoskeletal, and connective tissue. Scoliosis treatments are divided into surgical and conservative options. Surgery can correct the curved spine but has associated risks and economic burden. Conservative treatments, particularly bracing, prevent the progression of scoliosis, but still remains potential ingredient of curvation and patients poor compliance. Recent studies reported that various types of acupuncture can improve the curvation and the associated pain. However, there has been no systematic review on this issue. Therefore, this study will review the effectiveness and safety of acupuncture on scoliosis. Methods: Searching randomized controlled trials about the use of acupuncture for scoliosis will be performed using multiple electronic databases, manual search, and contact to authors e-mail if needed. We will select studies by the pre-defined criteria and summarize the data on study participants, interventions, control groups, outcome measurement, adverse events, and risk of bias. The primary outcome will be the Cobb angle, which is objective, and the secondary outcomes are associated with patient-centered indices (pain, functional status, and quality of life), which are subjective and adverse events. We will use Review Manager software (Version 5.3; Copenhagen; The Nordic Cochrane Center, The Cochrane Collaboration, 2014) to perform a meta-analysis and Cochrane Collaboration “risk of bias” tools to assess the risk of bias. Results: Our study will investigate the clinical evidence on the effectiveness and safety of acupuncture on scoliosis. Conclusion: Our study will be informative to scoliosis patients, clinicians, policy makers, and researchers working with conservative management for scoliosis.

Background: Irritable bowel syndrome (IBS) is a disorder which has considerable effect to patient's quality of life and social functioning. Its main symptoms include recurrent abdominal pain and/or bloating associated with abnormal stool form or frequency. The recommendable treatment of IBS is a medication including loperamide, cimetropium, tricyclic antidepressants, and selective serotonin receptor inhibitors, but it has limited effects and several side effects dissatisfy IBS patients. As an alternative therapy, Xiaoyao-san (XYS) is gaining interest for IBS patients. XYS, a traditional Chinese medicine (TCM), has wide scope of indications and it can be prescribed for various gastrointestinal disorders in TCM syndromes but there has been no systematic review on IBS. Therefore, this review aims on systematically validating the curative effect of XYS on IBS. Methods: Electronic databases, manual search, and contact to author e-mail will be used for searching randomized controlled trials about the use of XYS for IBS. We will select studies by the predefined criteria and collect the data on study participants, interventions, control groups, outcome measurement, adverse events, and risk of bias. Primary outcome will be the efficacy rate, and secondary outcomes will be the IBS-centered indices (abdominal pain score, abdominal distension score, diarrhea or constipation score, bowel symptom severity scale), index about quality of life, and adverse events. Review Manager software and Cochrane Collaboration “risk of bias” tools will be used for meta-analysis and assessment of risk of bias. Results: This review will identify the clinical evidence of XYS's effectiveness and safety for IBS according to formal evaluation aspects. Conclusion: This review will further support the evidence-based usage of XYS for IBS treatment. Ethics and dissemination: No ethical approval is required since there is no personal information collection and patient recruitment. Trial registration number: Research Registry; reviewregistry986.

Glycyl‐tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20–58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13–1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1‐containing EVs (GARS1‐EVs). Among the identified factors, insulin‐like growth factor II receptor, and vimentin also contributed to the anti‐cancer activity of GARS1‐EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis.

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.

Background Although a focus on late-life depression may help preventing suicide in older adults, many older people, especially those living in rural areas, have relatively low accessibility to treatment. This study examined the feasibility and effectiveness of a village-based intervention for depression targeting older adults living in rural areas. Methods A community-based randomised pilot trial was performed in two small rural villages in South Korea. Two villages were randomly selected and assigned to the intervention or active control group; all older adults living in the two villages (n = 451) were included in the intervention program or received standard Community Mental Health Service (CMHS) care, and the effectiveness of the program was examined using representative samples from both groups (n = 160). The 12-week intervention included case management according to individual risk level and group-based activities. Healthy residents living in the intervention village who played major roles in monitoring at-risk older individuals were supervised by CMHS staff. The score on the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was the primary outcome, while social network, functional status, and global cognitive function were secondary outcomes. Linear mixed models including the factors of intervention group, time, and their interaction were used to examine group differences in changes in primary and secondary outcomes from baseline to follow up. Results Overall, there was no significant group × time interaction with respect to the SGDS-K score, but older individuals with more depressive symptoms at baseline (SGDS-K ≥ 6) tended to have a lower likelihood of progressing to severe depression at post-intervention. The social network was strengthened in the intervention group, and there was a significant group × time interaction (F[df1, df2], 5.29 [1, 153], p = 0.023). Conclusion This study examined a 12-week village-based intervention for late-life depression in which the CMHS helped village-dwellers deal with late-life depression in their communities. Although the intervention improved social interactions among older adults, it did not reduce depressive symptoms. Further studies including more rural villages and long-term follow up are needed to confirm the effectiveness of this prevention program. Trial registration NCT04013165 (date: 9 July 2019, retrospectively registered).

ObjectiveTo determine the association of radiological and symptomatic osteoarthritis with sleep duration in a representative sample of the Korean population.MethodsUsing data from the national cross-sectional fifth Korea National Health and Nutrition Examination Survey 2010-2012. Of the 16,528 participants in KNHANES-V, 8,918 were adults aged≥ 50 years who had completed the survey questions on sleep duration and osteoarthritis, and had diagnostic X-ray results. We evaluated the association between sleep duration as the primary predictor for osteoarthritis involving the hip, knee, and spinal joints. A complex sample logistic regression analysis was performed to adjust for the covariates.ResultsProportions of participants with total daily sleep duration of ≤6 hours, 7-8 hours, and ≥9 hours were 47.1%, 45.2, and 7.7%, respectively. The rate of osteoarthritis diagnoses in the ≤6 hours, 7-8 hours, and ≥9 hours of sleep duration groups was 24.1%, 17.6%, and 21.8%, respectively (p ConclusionThis study confirmed the significant association between sleep duration and osteoarthritis in adults aged ≥50 years. Participants' positive for both radiological (KL grade ≥2) and symptomatic osteoarthritis showed a strong association between knee joint pain and not enough sleep duration.

Background ERCP training models are very different in terms of anatomical differences, ethical issues, storage problems, realistic tactile sensation, durability and portability. There is no easy way to select an optimized model for ERCP training. If the ERCP training model could be made as a soft silicone model using 3D printing technique, it would have numerous advantages over the models presented so far. The purpose of this study was to develop an optimized ERCP training model using a 3D printing technique and to try to find ways for implementing various practical techniques. Methods All organ parts of this model were fabricated using silicone molding techniques with 3D printing. Especially, various anatomy of the ampulla of Vater and common bile duct (CBD) were creatively designed for different diagnostic and therapeutic procedures. In order to manufacture each of the designed organ parts with silicone, a negative part had to be newly designed to produce the molder. The negative molders were 3D printed and then injection molding was applied to obtain organ parts in silicone material. The eight different types of ampulla and CBD were repeatedly utilized and replaced to the main system as a module-type. Results ERCP training silicone model using 3D technique was semi-permanently used to repeat various ERCP procedures. All ERCP procedures using this model could be observed by real-time fluoroscopic examination as well as endoscopic examination simultaneously. Using different ampulla and CBD modules, basic biliary cannulation, difficult cannulation, stone extraction, mechanical lithotripsy, metal stent insertion, plastic stent insertion, and balloon dilation were successfully and repeatedly achieved. Endoscopic sphincterotomy was also performed on a specialized ampulla using a Vienna sausage. After repeat procedures and trainings, all parts of organs including the ampulla and CBD modules were not markedly damaged or deformed. Conclusions We made a specialized ERCP training silicon model with 3D printing technique. This model is durable, relatively cheap and easy to make, and thus allows the users to perform various specialized ERCP techniques, which increases its chances of being a good ERCP training model.

The present study examined the daily well-being of Koreans (n = 353,340) for 11 weeks during the COVID-19 pandemic (January 20 –April 7). We analyzed whether and how life satisfaction, positive affect, negative affect, and life meaning changed during the outbreak. First, we found that the well-being of Koreans changed daily in a cubic fashion, such that it declined and recovered during the early phase but declined substantially during the later phase (after COVID- 19 was declared world pandemic by WHO). Second, unlike other emotions, boredom displayed a distinctive pattern of linear increase, especially for younger people, suggesting that boredom might be, in part, responsible for their inability to comply with social distancing recommendations. Third, the well-being of older people and males changed less compared to younger people and females. Finally, daily well-being dropped significantly more in the hard-hit regions than in other regions. Implications and limitations are discussed.

Background and objective Studies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group. Methods Adult (≥20 years) patients with pulmonary tuberculosis were identified from the National Health Insurance Research Database of Taiwan from 2004 to 2009. Treatment completion and mortality rates were noted at one year after treatment. Results Among the 81,081 patients with pulmonary tuberculosis identified, 13,923 (17.2%) were aged ≥80 years, and 26,897 (33.2%) were aged 65–79 years. The treatment completion, mortality rates and treatment delay were 54.8%, 34.7% and 61 (12–128) [median, (1st-3rd quartiles)] days in patients aged ≥80 years, 68.3%, 18.5% and 53 (8–122) days in patients aged 65–79 years, and 78.9%, 6.5% and 21 (1–84) days in patients aged

Background/aim Colon cancer is prone to distant metastases to other sites and the risk of recurrence is relatively high. Therefore, the identification of liver metastasis-related factors is important for the diagnosis or treatment of colon cancer. The aim of this study was to identify the metastasis-related factors that are differentially expressed in synchronous solitary liver metastasis compared to primary colon cancer. Materials and methods Tissues of primary colon cancer and associated with liver metastases of five patients were used for mass spectrometry. Identified proteins were validated by western blotting. The in silico analysis was performed using the STRING database and GeneMANIA. Results We identified 58 differentially expressed proteins (DEPs), including 51 under-expressed and 7 over-expressed proteins among a total of 164 identified proteins. Major hubs of protein-protein networks were ACTC1, PRDX6, TPI1, and ALDH1A1. DEPs were located in the extracellular region and cytoplasm and were involved in the regulation of enzymatic activity. The metabolic process was significantly enriched in biological processes and an involvement in the KEGG pathway. Conclusion These DEPs can potentially be used as biomarkers for the diagnosis of liver metastasis and they may provide a new strategy for developing anti-metastatic liver drugs in colon cancer patients.

BackgroundPatients with renal impairment have altered immunity, which might cause vulnerability to specific pathogens and worsen pneumonia-related outcomes. Nonetheless, the microbiological features of pneumonia in patients with decreased renal function remain unknown.MethodsTherefore, we conducted a retrospective cohort study enrolling adult patients hospitalized with pneumonia to assess this knowledge gap. The baseline estimated glomerular filtration rate (eGFR) and first sputum microbiology during hospitalization were used for statistical analyses.ResultsOverall, 1554 patients hospitalized with pneumonia (mean age, 76.1 ± 16.7) were included, and 162 patients had died at the end of hospitalization. The cutoff eGFR value predicting mortality was ConclusionsThese findings suggested the altered immunity and vulnerability to S. aureus infection in patients with decreased renal function, which may be the underlying cause of worse outcomes of pneumonia in this group of patients.

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

BackgroundInfluenza 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.MethodsDuring 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.ResultsAmong 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.ConclusionThe 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.

Supplemental Digital Content is available in the text, The aim of this study was to evaluate the changing pattern of antibiotic usage and antimicrobial resistance of bacterial pathogens among hospitalized patients in Korea. We simultaneously investigated the correlation between antimicrobial resistance and antibiotic consumption. Data on total antibiotic prescriptions, patient days, and antimicrobial sensitivity tests among inpatients from 6 university hospitals in Korea in 2004, 2008, and 2012 were collected. The consumption of each antibiotic class was converted to defined daily dose/1000 patient-days by using the anatomical therapeutic chemical classification system by the World Health Organization. We defined third-generation cephalosporins (3rd CEPs), fourth-generation cephalosporins, beta-lactam/beta-lactamase inhibitors, and fluoroquinolones (FQs) as broad-spectrum antibiotics and carbapenems, tigecycline, glycopeptides, oxazolidinone, and polymyxin as antibiotics against multidrug-resistant (MDR) pathogens. A 15.1% decrease in total antibiotic consumption was observed in 2012 compared to that observed in 2004. In contrast, a 10.2% and 70.7% increase in broad-spectrum antibiotics and antibiotics against MDR pathogens were observed, respectively, in the same period. The resistance rate of Escherichia coli to 3rd CEPs (17.6% in 2004, 21.7% in 2008, and 33.8% in 2012, P

Participatory sensing is gaining popularity as a method for collecting and sharing information from distributed local environments using sensor-rich mobile devices. There are a number of participatory sensing applications currently in wide use, such as location-based service applications (e.g., Waze navigation). Usually, these participatory applications collect tremendous amounts of sensing data containing personal information, including user identity and current location. Due to the high sensitivity of this information, participatory sensing applications need a privacy-preserving mechanism, such as anonymity, to secure and protect personal user data. However, using anonymous identifiers for sensing sources proves difficult when evaluating sensing data trustworthiness. From this perspective, a successful participatory sensing application must be designed to consider two challenges: (1) user privacy and (2) data trustworthiness. To date, a number of privacy-preserving reputation techniques have been proposed to satisfy both of these issues, but the protocols contain several critical drawbacks or are impractical in terms of implementation. In particular, there is no work that can transparently manage user reputation values while also tracing anonymous identities. In this work, we present a blockchain-based privacy-preserving reputation framework called BPRF to transparently manage user reputation values and provide a transparent tracing process for anonymous identities. The performance evaluation and security analysis show that our solution is both practical and able to satisfy the two requirements for user privacy and data trustworthiness.

Rationale: Gastrointestinal subepithelial tumors (SETs) with endoscopic features such as ulceration, a red color change, a peeled mucosal layer, and spontaneous bleeding could have malignant potential. However, we encountered a case of a lipoma that presented features different from the generally known features of gastrointestinal SETs. Therefore, we report an interesting rare case of a terminal ileal giant lipoma with a unique feature of spontaneous peeled ulceration on the surface on endoscopy that caused gastrointestinal bleeding. Patient: An 82-year-old woman with a 1-week history of abdominal pain and hematochezia presented to our hospital. Diagnoses: Ileocolonoscopy revealed a SET with a peeled surface and erythematous and ulcerative mucosal changes as well as exposed a submucosal mass at the terminal ileum. Macroscopically, the lesion appeared as a yellowish pedunculated polypoid mass measuring 3 × 2 cm with a peeled mucosal ulceration. Histopathological findings revealed a submucosal lipoma of the terminal ileum. Intervention: We thought that the endoscopic finding indicated malignant SETs or those with malignant potential rather than benign SETs. Therefore, the patient underwent an elective laparoscopic ileocecectomy. Lessons: We encountered a lipoma that did not present with the typical features of gastrointestinal SETs. Our findings suggest that clinicians should consider that benign SETs in the terminal ileum may present with various endoscopic findings similar to those of malignant SETs, which can cause fatal symptoms and signs.

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.

Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored.Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF.Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation. Simultaneously, histological analysis demonstrated thickening of alveolar walls, destruction of alveolar structures, and excessive collagen deposition in the irradiated lung. PTX treatment effectively attenuated the fibrotic changes based on both micro-CT and histopathological analyses. Western analysis also revealed increased levels of plasminogen activator inhibitor- (PAI-) 1 and fibronectin (FN) and PTX treatment reduced expression of PAI-1 and FN by restoring protein kinase A (PKA) phosphorylation but not TGF-β/Smad in both irradiated lung tissues and epithelial cells.Conclusions. Our results demonstrate the antifibrotic effect of PTX on radiation-induced lung fibrosis and its effect on modulation of PKA and PAI-1 expression as possible antifibrotic mechanisms.

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.

Aminoacyl-tRNA synthetases (ARSs) acylate transfer (t)RNAs with amino acids. Charging tRNAs with the right amino acids is the first step in translation; therefore, the accurate and error-free functioning of ARSs is an essential prerequisite for translational fidelity. A recent study found that methionine (Met) can be incorporated into non-Met residues of proteins through methionylation of non-cognate tRNAs under conditions of oxidative stress. However, it was not understood how this mis-methionylation is achieved. Here, we report that methionyl-tRNA synthetase (MRS) is phosphorylated at Ser209 and Ser825 by extracellular signal-related kinase (ERK1/2) under conditions of stress caused by reactive oxygen species (ROS), and that this phosphorylated MRS shows increased affinity for non-cognate tRNAs with lower affinity for tRNAMet, leading to an increase in Met residues in cellular proteins. The expression of a mutant MRS containing the substitutions S209D and S825D, mimicking dual phosphorylation, reduced ROS levels and cell death. This controlled inaccuracy of MRS seems to serve as a defense mechanism against ROS-mediated damage at the cost of translational fidelity.

Background KIOM-CRC#BP3B (BP3B) is a novel herbal prescription that is composed of three plant extracts. Our preliminary study identified that BP3B exhibited potent anti-proliferative activity against various types of cancer cell lines in vitro. Because the in vivo anti-tumor effect of BP3B is not evaluated before clinical trial, we want to test it using patient’s samples. Methods To confirm the in vivo anti-cancer effect of BP3B, we used genetically characterized patient-derived colon tumor xenograft (PDTX) mouse model. Anti-cancer activity was evaluated with apoptosis, proliferation, angiogenesis and histological analysis. Results Oral administration of BP3B significantly inhibited the tumor growth in two PDTX models. Furthermore, TUNEL assay showed that BP3B induced apoptosis of tumor tissues, which was associated with degradation of PARP and Caspase 8 and activation of Caspase 3. We also observed that BP3B inhibited cancer cell proliferation by down-regulation of Cyclin D1 and induction of p27 proteins. Inhibition of angiogenesis in BP3B-treated group was observed with immunofluorescence staining using CD31 and Tie-2 antibodies. Conclusion These findings indicated that BP3B has a strong growth-inhibitory activity against colon cancer in in vivo model and will be a good therapeutic candidate for treatment of refractory colon cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1447-8) contains supplementary material, which is available to authorized users.

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

Background Both smoking and diabetes can increase the risk and influence the manifestations and outcomes of tuberculosis (TB). It is not clear whether the influence of smoking on pulmonary TB differs between non-diabetic and diabetic patients. Herein, we assessed the manifestations and outcomes of TB in relation to smoking in both diabetic and non-diabetic TB patients. Methodology/Principal Findings All diabetic culture-positive pulmonary TB patients notified from 2005–2010 at three teaching hospitals in Taiwan were enrolled. A culture-positive pulmonary TB patient without DM who was notified to the health authority immediately prior to each diabetic TB patient was selected for comparison. The 972 patients in this study cohort included 365 (37.6%) non-diabetic non-smokers, 149 (15.3%) non-diabetic smokers, 284 (29.2%) diabetic non-smokers, and 174 (17.9%) diabetic smokers. The adjusted relative risk of a pretreatment positive smear for a smoker compared with a non-smoker was 2.19 (95% CI 1.38–3.47) in non-diabetic patients and 2.23 (95% CI 1.29–3.87) in diabetic culture-positive pulmonary TB patients. The adjusted relative risk for a positive smear among diabetic smokers was 5.61 (95% CI 3.35–9.41) compared with non-diabetic non-smokers. Smoking was significantly associated with an increased frequency of bilateral lung parenchyma involvement (AdjOR 1.84, 95% CI 1.16–2.93), far-advanced pulmonary TB (AdjOR 1.91, 95% CI 1.04–3.50), cavitary lesions (AdjOR 2.03, 95% CI 1.29–3.20), and unfavorable outcomes of TB (AdjOR 2.35, 95% CI 1.02–5.41) in non-diabetic patients. However, smoking was not associated with cavitary lung parenchyma lesions regarding the location, number or size of the cavity in diabetic TB patients. Conclusions/Significance Smoking and diabetes have joint effects on a pretreatment positive smear. Diabetic smokers had more than a 5-fold increased risk of a pretreatment positive smear than did non-diabetic non-smokers, indicating remarkable joint effects of diabetes and smoking on the risk of TB transmission.

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.

Selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are reported to have potent antiemetic effects for postoperative nausea and vomiting (PONV). The purpose of this study was to prospectively evaluate the efficacy of palonosetron, granisetron, and ramosetron for the prevention of PONV in patients undergoing laparoscopic gynecologic surgery. In this prospective, randomized observational study, 105 healthy female patients who were undergoing laparocopic hystectomy under general anaesthesia were enrolled (clinical trial number: NCT01752374, www.clinicaltrials.gov ). Patients were divided into three groups: the palonostron (0.075 mg i.v.; n = 35), the granisetron group (3 mg i.v.; n = 35), and the ramosetron group (0.3 mg i.v.; n = 35). The treatments were given before the end of surgery. The incidence of PONV, severity of nausea/vomiting, and the use of rescue antiemetic requirements during the first 48 h after surgery were evaluated. The overall incidence of PONV was 33.3 % for this series. The number of complete responders at 48 h after the surgery was 21 (60.0 %) for palonosetron, 24 (68.6 %) for granisetron, and 26 (71.4 %) for ramosetron, representing no statistical difference (P = 0.086). There were no significant differences in the overall incidence of postoperative nausea and vomiting and complete responders for palonosetron, granisetron and ramosetron group. Clinical trial number: NCT01752374 , www.clinicaltrials.gov .

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.

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.

Autophagy is a vital pathway for the removal of beta-amyloid peptide (A beta) 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 A beta and C-terminal APP fragment beta subunit (APP-CTF beta) by up-regulating autophagy. When N2a cells were exposed to soluble A beta 1-42, protein levels of beclin-1, autophagy-related protein5 (Atg5), and SIRT1 decreased significantly. Pretreatment with cilostazol (10-30 mu M) or resveratrol (20 mu M) prevented these A beta 1-42 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 A beta 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). A beta and APP-CTF beta expressions were increased after 12 similar to 24 h in Tet(-) condition, and these increased expressions were significantly reduced by pretreating cilostazol. Cilostazol-induced reductions in the expressions of A beta and APP-CTF beta were blocked by bafilomycin A1 (a blocker of autophagosome to lysosome fusion). After knockdown of the SIRT1 gene (to similar 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 A beta was prevented by cilostazol, and this inhibition was reversed by 3-methyladenine, indicating that the protective effect of cilostazol against A beta 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 A b

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.

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.

BACKGROUND: Radiographic manifestations of pulmonary tuberculosis (TB) in patients with diabetes mellitus (DM) have previously been reported, with inconsistent results. We conducted a study to investigate whether glycemic control has an impact on radiographic manifestations of pulmonary TB. METHODS: Consecutive patients with culture-positive pulmonary TB who had DM in three tertiary care hospitals from 2005-2010 were selected for review and compared with a similar number without DM. Glycemic control was assessed by glycated haemoglobin A1C (HbA1C). A pre-treatment chest radiograph was read independently by two qualified pulmonologists blinded to patients' diabetic status. Films with any discordant reading were read by a third reader. RESULTS: 1209 culture positive pulmonary TB patients (581 with DM and 628 without DM) were enrolled. Compared with those without DM, TB patients with DM were significantly more likely to have opacity over lower lung fields, extensive parenchymal lesions, any cavity, multiple cavities and large cavities (>3 cm). The relative risk of lower lung field opacities was 0.80 (95% CI 0.46-1.42) for those with DM with A1C9%; and that of any cavity over no cavity was 0.87 (95% CI 0.46-1.62) for patients with DM with A1C9%, relative to patients without DM. CONCLUSIONS: Glycemic control significantly influenced radiographic manifestations of pulmonary TB in patients with DM.

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.

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.

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

Background Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH

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.

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