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Previous studies suggest an association between atopic dermatitis (AD) and exposure to microorganisms and antibiotics. However, these studies have limitations, and the sole influence on the development of AD was elusive. We performed a nationwide population‐based case–control study in a Korean population to investigate the association between AD and early‐life infection or antibiotic exposure. A total of 244 805 children with AD from the 2 283 601 children born between January 2010 and December 2014 and an equal number of sex‐ and age‐matched healthy children were enrolled. A conditional logistic regression analysis showed that the episode of infection and antibiotic exposure were associated with an increased risk of AD (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.58–1.63 for infection; and OR, 1.11; 95% CI, 1.09–1.13 for antibiotic exposure). A dose‐dependent relationship was observed between risk for AD, the number of infection episodes and antibiotic cycles and the duration of antibiotic exposure. On further analysis using a conditional logistic model, the risk of AD was less when the antibiotics were used during the infection episode than that without the use of antibiotics, especially if the duration of the infection was short. Although our study could not consider the effect of cause or severity of infection, class of antibiotics and genetic or environmental factors of enrolled subjects, our results suggested that infection and antibiotic exposure were associated with an increased risk of AD. In addition, the results also implied that the use of antibiotics during an infection episode can decrease the risk of AD induced by the infection and that appropriate management of infections can minimize the risk of AD induced by infection or antibiotics. [ABSTRACT FROM AUTHOR]

Background: Central venous catheters should be positioned at the cavoatrial junction or the right atrium. If catheters are inserted to a depth derived by adding the length between the needle insertion point and the clavicular notch and the length between the clavicular notch and the carina, the catheter tip can be placed near the carina. Based on this, we aim to make a formula to place a catheter tip near the cavoatrial junction. Methods: This prospective nonrandomized interventional study included patients who needed a central venous catheter from June 2017 to July 2018. The location of the cavoatrial junction was identified using a fluoroscopic technique. The following variables were measured: L1, the length between the needle insertion point and the clavicular notch; L2, the length between the clavicular notch and the carina; and α, the length between the carina and the cavoatrial junction. Results: A total of 70 patients were enrolled. The mean age was 65.5 ± 11.6 years, and 62.9% were male. The mean L1 and L2 were 7.6 ± 1.4 and 7.0 ± 1.4 cm, respectively. The mean α was 4.4 ± 1.5 cm (95% CI 4.1–4.8), and it was not affected by demographic factors, such as sex, age, height or weight. Conclusions: Central venous catheters in adult patients can be placed near the cavoatrial junction using a simple formula: the distance between the insertion point and the clavicular notch + the distance between the clavicular notch to the carina + 4.4 cm. [ABSTRACT FROM AUTHOR]

Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4‐metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel's effectiveness. From Korean nationwide claims data (2007–2015), we selected 59,233 patients who initiated clopidogrel and statins after coronary stenting and compared thrombotic risks by PPI or CYP3A4‐metabolized statin use or both. PPIs were associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12–1.45), unlike CYP3A4‐metabolized statins (HR 1.03, 95% CI 0.98–1.07). PPIs with high CYP2C19‐inhibitory potential were more relevant than those with low potential (HR 1.28, 95% CI 1.02–1.61). Joint effects of PPIs and CYP3A4‐metabolized statins were nonsignificant (relative excess risk due to interaction −0.14, 95% CI −0.34 to 0.07). Concurrent PPIs were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP3A4‐metabolized statins did not exacerbate PPI‐associated risks. [ABSTRACT FROM AUTHOR]

Background: To determine the diagnostic role of CT added to ultrasound for the diagnosis of recurrent differentiated thyroid cancer (DTC) and to evaluate potential benefits for patients. Methods: A total of 193 patients with recurrent DTC were retrospectively included. The diagnostic performances of ultrasound and combination of ultrasound and CT (ultrasound/CT) in detecting recurrence were compared. Benefits of CT were assessed based on the presence of any recurrence detected only with additional CT. Results: In detecting cervical recurrence, ultrasound/CT showed higher sensitivity (P = .001) and lower specificity (P < .001) than ultrasound alone, overall resulting in higher area under the curve (P < .001). Seventy‐nine patients (40.9%) benefited from additional CT in detecting recurrence. Conclusion: For reoperation of cervical recurrence in patients with DTC, addition of CT to ultrasound offers better surgical planning by enhancing detection of recurrent cancers that were overlooked with ultrasound alone. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic value of integrated positron emission tomography/magnetic resonance imaging (PET/MRI) compared with conventional multiparametric MRI and PET/computed tomography (CT) for the detailed and accurate segmental detection/localization of prostate cancer.Materials and Methods: Thirty-one patients who underwent integrated PET/MRI using 18 F-choline and 18 F-FDG with an integrated PET/MRI scanner followed by radical prostatectomy were included. The prostate was divided into six segments (sextants) according to anatomical landmarks. Three radiologists noted the presence and location of cancer in each sextant on four different image interpretation modalities in consensus (1, multiparametric MRI; 2, integrated 18 F-FDG PET/MRI; 3, integrated 18 F-choline PET/MRI; and 4, combined interpretation of 1 and 18 F-FDG PET/CT). Sensitivity, specificity, accuracy, positive and negative predictive values, likelihood ratios, and diagnostic performance based on the DOR (diagnostic odds ratio) and NNM (number needed to misdiagnose) were evaluated for each interpretation modality, using the pathologic result as the reference standard. Detection rates of seminal vesicle invasion and extracapsular invasion were also evaluated.Results: Integrated 18 F-choline PET/MRI showed significantly higher sensitivity than did multiparametric MRI alone in high Gleason score patients (77.0% and 66.2%, P = 0.011), low Gleason score patients (66.7% and 47.4%, P = 0.007), and total patients (72.5% and 58.0%, P = 0.008) groups. Integrated 18 F-choline PET/MRI and 18 F-FDG PET/MRI showed similar sensitivity and specificity to combined interpretation of multiparametric MRI and 18 F-FDG PET/CT (for sensitivity, 58.0%, 63.4%, 72.5%, and 68.7%, respectively, and for specificity, 87.3%, 80.0%, 81.8%, 72.7%, respectively, in total patient group). However, integrated 18 F-choline PET/MRI showed the best diagnostic performance (as DOR, 11.875 in total patients, 27.941 in high Gleason score patients, 5.714 in low Gleason score groups) among the imaging modalities, regardless of Gleason score. Integrated 18 F-choline PET/MRI showed higher sensitivity and diagnostic performance than did integrated 18 F-FDG PET/MRI (as DOR, 6.917 in total patients, 15.143 in high Gleason score patients, 3.175 in low Gleason score groups) in all three patient groups.Conclusion: Integrated PET/MRI carried out using a dedicated integrated PET/MRI scanner provides better sensitivity, accuracy, and diagnostic value for detection/localization of prostate cancer compared to multiparametric MRI. Generally, integrated 18 F-choline PET/MRI shows better sensitivity, accuracy, and diagnostic performance than does integrated 18 F-FDG PET/MRI as well as combined interpretation of multiparametric MRI with 18 F-FDG PET/CT.Level Of Evidence: 2 J. Magn. Reson. Imaging 2017;45:597-609. [ABSTRACT FROM AUTHOR]

Objective The US Food and Drug Administration is considering an application for a biosimilar version of infliximab, which has been available in South Korea since November 2012. The aim of the present study was to examine the utilization patterns of both branded and biosimilar infliximab and other tumor necrosis factor (TNF) inhibitors in South Korea before and after the introduction of this biosimilar infliximab. Methods Using claims data from April 2009 to March 2014 from the Korean Health Insurance Review and Assessment Service database, which includes the entire South Korean population, the number of claims for biosimilar infliximab was assessed. A segmented linear regression model was used to examine the utilization patterns of infliximab (the branded and biosimilar versions) and other TNF inhibitors (adalimumab and etanercept) before and after the introduction of the biosimilar infliximab. Results In total, 20,976 TNF inhibitor users were identified from the South Korean claims database, including 983 with a prescription claim for biosimilar infliximab. Among all of the claims for any version of infliximab, the proportion of biosimilar infliximab claims increased to 19% through March 2014. Before November 2012, each month there were 33 (95% confidence interval [95% CI] 32, 35) more infliximab claims, 44 (95% CI 40, 48) more etanercept claims, and 50 (95% CI 47, 53) more adalimumab claims. After November 2012, there were significant changes in the slopes for trend in usage, with additional increases in the use of branded and biosimilar infliximab (9 more claims per month, 95% CI 2, 17) and decreases in the use of etanercept (−52 claims per month, 95% CI −66, −38) and adalimumab (−21 claims per month, 95% CI −35, −6). Conclusion During the first 15 months since its introduction in South Korea, one-fifth of all infliximab claims were for the biosimilar version. Introduction of biosimilar infliximab may affect the use of other TNF inhibitors, and the magnitude of change in usage will likely differ in other countries. [ABSTRACT FROM AUTHOR]

Both glucosamine and cyclosporin have been reported to show immunomodulatory effect with inhibition of each different key transcription factor for cytokine gene expression and T-cell function. The overall purpose of this pilot study was to assess the feasibility of the combination of cyclosporin with glucosamine for the treatment of patients with atopic dermatitis. Twelve patients more than 12 years old who required systemic cyclosporin were included in the study. Two of them dropped out due to violation of medication schedule. The single ( S) and combination ( C) regimens were crossed over every 2 weeks without a washout period between the cross-over for 6 months. Five patients were randomly assigned to the S regimen first ( SC sequence), whereas the other five were given the C first ( CS sequence). The change of SCORAD index was analyzed as the primary efficacy end-point by general linear model and piecewise linear mixed model. The SCORAD index was reduced with both SC and CS sequence regimens. In particular, index reduction with the C was more than that associated with S regimen; this difference increased as time lapsed. The glucosamine combination was predicted to cause an additive decrease in the mean percent change of the SCORAD index (~6%), with decreasing interleukin ( IL)-4 and IL-5 cytokine levels but without increasing treatment-related adverse events. This study suggests that the C would produce better clinical outcomes than the S regimen in patients with atopic dermatitis, although confirmatory clinical trials are warranted to determine the effect of combination. [ABSTRACT FROM AUTHOR]

Objective Moyamoya disease (MMD) is a cerebrovascular occlusive disease of the bilateral internal carotid arteries that causes a compensatory abnormal vascular network at the base of brain. The rare incidence and various surgical techniques applied have limited the clinical research on MMD. Methods We conducted a retrospective analysis of the surgical outcome of 410 pediatric MMD patients. All patients were treated in a relatively uniform scheme at a single institution. The surgical procedures consisted of bilateral encephaloduroarteriosynangiosis augmented by bifrontal encephalogaleo-/periosteal synangiosis. Logistic regression analyses were applied to reveal the prognostic factors for surgical outcome. Results The overall clinical outcome was excellent in 66%, good in 15%, fair in 15%, and poor in 4% of the patients. Therefore, 81% of the patients had a favorable clinical outcome (excellent and good). Multivariate analyses revealed that infarction on presentation was associated with unfavorable clinical outcome (odds ratio [OR], 2.85; 95% confidence interval [CI], 1.49-5.46; p < 0.01) and decreased vascular reserve only on single-photon emission computerized tomography (OR, 0.07; 95% CI, 0.01-0.52; p < 0.01), with favorable clinical outcome. Interpretation Our results indicate that an early diagnosis and active intervention before establishment of irreversible hemodynamic change are essential to achieve a favorable clinical outcome in children with MMD. ANN NEUROL 2010;68:92-101 [ABSTRACT FROM AUTHOR]

Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events ( P =0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Background Inflammation levels are lower in East Asians than in Western people. We studied the association between high-sensitivity hs-CRP (C-reactive protein) and adverse outcomes in Korean patients with chronic kidney disease. Methods and Results We included 2018 participants from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all-cause mortality. The secondary end points were separate outcomes of eMACE, all-cause death, and adverse kidney outcome. We also evaluated predictive ability of hs-CRP for the primary outcome. The median hs-CRP level was 0.60 mg/L. During the mean follow-up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs-CRP with the primary outcome. The hazard ratios for hs-CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87-2.03) and 2.08 (95% CI, 1.30-3.33) compared with the hs-CRP of <1.0 mg/L. In secondary outcomes, this association was consistent for eMACE and all-cause death; however, hs-CRP was not associated with adverse kidney outcomes. Finally, prediction models failed to show improvement of predictive performance of hs-CRP compared with conventional factors. Conclusions In Korean patients with chronic kidney disease, the hs-CRP level was low and significantly associated with higher risks of eMACEs and mortality. However, hs-CRP did not associate with adverse kidney outcome, and the predictive performance of hs-CRP was not strong. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Background: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea., Materials and Methods: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons., Results: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication., Conclusion: There was no relationship between the eradication rate and antibiotic use density in Korea., (© 2019 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Background It is unclear whether high-sensitivity troponin T (hs-TnT) is associated with subclinical cardiac changes in chronic kidney disease (CKD). We evaluated the relationship between hs-TnT and left ventricular structure and function in a CKD population, according to estimated glomerular filtration rate. Methods and Results We analyzed 2017 patients with CKD stages 1 to 5 (predialysis) in the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) cohort. The predictor was hs-TnT level measured at baseline, and the outcomes were left ventricular hypertrophy (LVH) and systolic and diastolic dysfunction shown by echocardiography at baseline and after 4 years. Participants were categorized into quartiles according to hs-TnT levels. The associations between quartiles of hs-TnT and outcomes were assessed using multivariable logistic regression analysis with confounders including demographics, medical history, and laboratory findings. A receiver operating characteristic curve was used to assess the diagnostic power of hs-TnT for the outcomes as a continuous variable. For subgroup analysis, patients were stratified based on an estimated glomerular filtration rate of 60 mL/min per 1.73 m 2 . Elevated hs-TnT was associated with LVH and diastolic dysfunction at baseline in an adjusted model but was not associated with systolic dysfunction. These associations remained significant for both estimated glomerular filtration rate subgroups. Receiver operating characteristic curve analysis showed that hs-TnT as a continuous variable exhibited fair significance for detection of LVH (area under the curve: 0.689) and diastolic dysfunction (area under the curve: 0.744). Multivariable analysis showed that higher hs-TnT levels at baseline were related to development of LVH but not diastolic dysfunction (n=864). Conclusions In CKD patients, hs-TnT is strongly associated with alterations of left ventricular structure and diastolic dysfunction for both estimated glomerular filtration rate strata. Baseline hs-TnT levels are predictive of new LVH on follow-up.

Background High-density lipoprotein cholesterol ( HDL -C) levels are generally decreased in patients with chronic kidney disease ( CKD ). However, studies on the relationship between HDL -C and CKD progression are scarce. Methods and Results We studied the association between serum HDL -C levels and the risk of CKD progression in 2168 participants of the KNOW - CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). The primary outcome was the composite of a 50% decline in estimated glomerular filtration rate from baseline or end-stage renal disease. The secondary outcome was the onset of end-stage renal disease. During a median follow-up of 3.1 (interquartile range, 1.6-4.5) years, the primary outcome occurred in 335 patients (15.5%). In a fully adjusted Cox model, the lowest category with HDL -C of <30 mg/dL (hazard ratio, 2.21; 95% CI, 1.30-3.77) and the highest category with HDL -C of ≥60 mg/dL (hazard ratio, 2.05; 95% CI , 1.35-3.10) were associated with a significantly higher risk of the composite renal outcome, compared with the reference category with HDL -C of 50 to 59 mg/dL. This association remained unaltered in a time-varying Cox analysis. In addition, a fully adjusted cubic spline model with HDL -C being treated as a continuous variable yielded similar results. Furthermore, consistent findings were obtained in a secondary outcome analysis for the development of end-stage renal disease. Conclusions A U-shaped association was observed between serum HDL -C levels and adverse renal outcomes in this large cohort of patients with CKD . Our findings suggest that both low and high serum HDL -C levels may be detrimental to patients with nondialysis CKD .

Background: The efficacy of proton-pump inhibitor-amoxicillin-clarithromycin therapy for H. pylori eradication has decreased over time., Objective: We assessed the trend of H. pylori eradication rates over the last 10 years and the relationship between the eradication rates and the amount of macrolide antibiotic use in a country with a high prevalence of H. pylori infection., Methods: This vast nationwide multicenter study was conducted with 34,139 adults treated for H. pylori infection from January 2001 to December 2010. The defined daily dose per km(2) (DSD) of macrolide antibiotics was calculated (n = 141,019) using the Health Insurance Review & Assessment data base from 2008 to 2010 in the two cities which had the lowest (Jeju city) or highest (Chuncheon city) eradication rate., Results: The eradication rates of proton-pump inhibitor-amoxicillin-clarithromycin therapy ranged 84.9-87.5% from 2001 to 2007, and those of 2008 to 2010 ranged 80.0-81.4% with a decreasing trend (p < 0.0001). The decreasing trend of eradication rates for the overall first-line therapy was observed only in three of the seven geographic areas in Korea (p < 0.0001). The DSD of macrolide antibiotics was significantly higher in Jeju than Cheunchon city (0.85 vs 0.52, p < 0.0001)., Conclusions: H. pylori eradication rates with clarithromycin-containing triple therapy in Korea showed a decreasing trend over the past 10 years, although the trend varied among geographic areas. This difference may be associated with the amount of macrolide antibiotic use., (© 2015 John Wiley & Sons Ltd.)