Atmospheric environment and persistence of pediatric asthma: A population-based cohort study.

BACKGROUND: Asthma is a heterogeneous disease with different outcomes. For children with asthma at the age of 7 years, 67-75% are symptom-free as adults. Data on the important link between childhood and adult asthma are sparse. OBJECTIVE: We aimed to investigate factors associated with persistence of childhood asthma over three years of follow-up by linking data between Korea childhood Asthma Study (KAS) and their matched claims data from Health Insurance Review and Assessment Service (HIRA). METHODS: We analyzed data from 450 preadolescent children aged 7 to 10 years and classified them into remission or persistence groups. Baseline clinical characteristics and exposure to air pollution materials including PM2.5 and PM10 during three years of follow-up were compared. The main outcome was asthma persistence which was defined as the presence of asthma episodes with healthcare utilization and prescription of asthma medications within three years after KAS enrollment. RESULTS: At the third year of follow-up, after stepwise regression analysis, lower age at enrollment (adjusted odds ratio (aOR): 0.79; 95% confidence interval (CI): 0.64-0.96), male sex (aOR: 1.66; 95%CI: 1.05-2.63), proximity from an air-polluting facility (aOR: 2.4; 95%CI: 1.34-4.29), higher level outdoor PM2.5 (aOR: 1.1; 95%CI: 1.02-1.20), and higher rate of doctor-diagnosed food allergy (FA) (aOR: 2.33; 95%CI: 1.06-5.12) were significantly associated with persistence. CONCLUSION: We discovered various independent risk factors for the persistence of childhood asthma. By linking HIRA claims data, we could clarify risk factors for persistence in a well-defined study population.

Diagnostic Assessment of Endoscopic Ultrasonography-Fine Needle Aspiration Cytology in the Pancreas: A Comparison between Liquid-Based Preparation and Conventional Smear.

Background and Objectives: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. Methods: The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. Results: The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. Conclusions: Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.

Frequency of exacerbation and degree of required asthma medication can characterize childhood longitudinal asthma trajectories.

BACKGROUND: To the best of our knowledge, there have been no investigations of longitudinal asthma trajectories based on asthma exacerbation frequency and medications required for asthma control in children. OBJECTIVE: To investigate longitudinal asthma trajectories based on the exacerbation frequency throughout childhood and asthma medication ranks. METHODS: A total of 531 children aged 7 to 10 years were enrolled from the Korean childhood Asthma Study. Required asthma medications for control of asthma from 6 to 12 years of age and asthma exacerbation frequency from birth to 12 years of age were obtained from the Korean National Health Insurance System database. Longitudinal asthma trajectories were identified on the basis of asthma exacerbation frequency and asthma medication ranks. RESULTS: Four asthma clusters were identified: lesser exacerbation with low-step treatment (8.1%), lesser exacerbations with middle-step treatment (30.7%), highly frequent exacerbations in early childhood with small-airway dysfunction (5.7%), and frequent exacerbations with high-step treatment (55.6%). The frequent exacerbations with high-step treatment cluster were characterized by a high prevalence of male sex, increased blood eosinophil (counts) with fractional exhaled nitric oxide, and high prevalence of comorbidities. The highly frequent exacerbation in early childhood with small-airway dysfunction cluster was characterized by recurrent wheeze in preschool age, with high prevalence of acute bronchiolitis in infancy and a greater number of family members with small-airway dysfunction at school age. CONCLUSION: The present study identified 4 longitudinal asthma trajectories on the basis of the frequency of asthma exacerbation and asthma medication ranks. These results would help clarify the heterogeneities and pathophysiologies of childhood asthma.

Fetal growth rather than prematurity determines lung function in children with asthma.

BACKGROUND AND OBJECTIVE: Preterm birth or fetal growth has been associated with reduced lung function and asthma during childhood in the general population. We aimed to elucidate whether prematurity or fetal growth has a significant influence on lung function or symptoms in children with stable asthma. METHODS: We included children with stable asthma who participated in the Korean childhood Asthma Study cohort. Asthma symptoms were determined by asthma control test (ACT). Percent predicted values of pre- and post-bronchodilator (BD) lung function including forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), and forced expiratory flow at 25%-75% of FVC (FEF25%-75% ) were measured. Lung function and symptoms were compared according to the history of preterm birth and birth weight (BW) for gestational age (GA). RESULTS: The study population consisted of 566 children (age range: 5-18 years). There were no significant differences in lung function and ACT between preterm and term subjects. We observed no significant difference in ACT but significant differences were observed in pre- and post-BD FEV1 , pre- and post-BD FVC, and post-BD FEF25%-75% according to BW for GA in total subjects. Two-way ANOVA revealed that BW for GA rather than prematurity was a significant determining factor for pre- and post-BD lung function. After regression analysis, BW for GA was still a significant determining factor of pre- and post-BD FEV1 and pre- and post-BD FEF25%-75% . CONCLUSION: Fetal growth rather than prematurity appears to have a significant effect on lung function in children with stable asthma.

Longitudinal asthma exacerbation phenotypes in the Korean childhood asthma study cohort.

BACKGROUND: Asthma exacerbation (AE) leads to social and economic costs and long-term adverse outcomes. We aimed to predict exacerbation-prone asthma (EPA) in children. METHODS: The Korean childhood Asthma Study (KAS) is a prospective nationwide pediatric asthma cohort of children aged 5-15 years followed every 6 months. Patients with AE during the 6 months prior to all three visits, with AE prior to one or two visits, and without AE prior to any visit were defined as having EPA, exacerbation-intermittent asthma (EIA), and exacerbation-resistant asthma (ERA), respectively. Risk factors and prediction models of EPA were explored. RESULTS: Of the 497 patients who completed three visits, 42%, 18%, and 15% had exacerbations prior to visits 1, 2, and 3 and 5%, 47%, and 48% had EPA, EIA, and ERA, respectively. Univariate and multivariable logistic regression revealed forced expiratory volume in 1 s (FEV1) z-score, forced vital capacity (FVC) z-score, white blood cell (WBC) count, and asthma control test (ACT) score as relevant EPA risk factors. The EPA prediction model comprised FVC z-score, WBC count, ACT score, sex, and parental education level (area under the receiver operating characteristic curve [AUROC] 0.841 [95% confidence interval (CI): 0.728-0.954]). CONCLUSION: With appropriate management, AE decreases over time, but persistent AEs may occur. Apart from asthma control level, baseline lung function and WBC count predicted EPA.

Current Asthma Prevalence Using Methacholine Challenge Test in Korean Children from 2010 to 2014.

BACKGROUND: Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children. METHODS: Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value. RESULTS: The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%. CONCLUSIONS: Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.

Clinical Characteristics and Treatment Outcomes of Patients with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection: Experience at a Single Center in Korea.

BACKGROUND: Because of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea. METHODS: We performed a retrospective cohort study of all HCV-monoinfected and HCV/HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020. RESULTS: We enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients. Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs. HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480). CONCLUSION: In Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCV-monoinfected patients.

Asthma control test reflects not only lung function but also airway inflammation in children with stable asthma.

Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma.Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations.Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score.Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.

Urine Bacteria-Derived Extracellular Vesicles and Allergic Airway Diseases in Children.

BACKGROUND: Microbiota and human allergic airway diseases have been proven to be interrelated. Bacteria-derived extracellular vesicle (EV)s are known to play important roles in interbacterial and human-bacteria communications, but their relationship with allergies has not been examined yet. Urine EVs were investigated to determine whether they could be used as biomarkers for monitoring allergic airway diseases in children. METHODS: Subjects were 4 groups of chronic rhinitis (CR), allergic rhinitis (AR), atopic asthma (AS) and healthy controls. Single voided urine samples were collected. Urine EVs were isolated and their DNA was extracted for 16S-rDNA pyrosequencing. RESULTS: A total of 118 children participated in this study; 27, 39, 19, and 33 were in the CR, AR, AS, and control group, respectively. The AR had a significantly high Chao-1 index than that of controls. Principal component analysis revealed dysbiosis in the CR, AR, and AS compared to the controls. One phylum and 19 families and genera were significantly enriched or depleted in the disease groups compared to the controls; the Actinobacteria phylum and the Sphingomonadaceae family were more abundant in the AS and CR, the Comamonadaceae family, the Propionibacteraceae family, Propionibacterium and Enhydrobacter were more enriched in the CR, and the Methylobacteriaceae family and Methylobacterium were more abundant in each disease group, while the Enterobacteriaceae family was depleted in each disease group. CONCLUSIONS: CR, AR, and AS had a distinct composition of urine EVs. Urine EVs could be an indicator for assessing allergic airway diseases in children.

Korean childhood asthma study (KAS): a prospective, observational cohort of Korean asthmatic children.

BACKGROUND: Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. METHODS: We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects' baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. DISCUSSION: Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects' personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Preventive and therapeutic effects of vitamin D in a mouse model of allergic asthma.

BACKGROUND: Vitamin D produces an anti-allergic effect that prevents inflammation due to asthma. OBJECTIVE: We investigated whether vitamin D has an anti-inflammatory effect on the sensitization and challenge stages of asthma development in a murine model. METHODS: Mice were divided into the following five groups according to ovalbumin (OVA) and vitamin D (VD) administration: control group, OVA group, preventive VD group (VD injection before OVA sensitization), inhibitory VD group (VD injection after OVA challenge), and dual VD groups (VD injection before OVA sensitization and after OVA challenge). Each group was evaluated for airway hyperresponsiveness (AHR), cell counts, cytokines, total IgE, and OVA-specific IgE using bronchoalveolar lavage fluid (BALF). Cytokines in the lysate and eosinophils in the lung tissue were also evaluated. RESULTS: AHR occurred less in the groups to which VD was administered than in the OVA group. The eosinophils, neutrophils, IL-5 in BALF, IL-4, TGF-ß, and eosinophils in lysate decreased with the administration of VD in the preventive, inhibitory, and dual VD groups compared with the OVA group. Although the lymphocytes, macrophages, IL-4 in BALF, and IL-5 in lysate decreased with administration of VD in the inhibitory and dual VD groups, they were not affected by preventive VD administration. These anti-allergic effects of VD were most noticeable with VD administration for dual (preventive and inhibitory) purposes. CONCLUSIONS: VD may produce preventive and inhibitory effects on the development and exacerbation of asthma in a murine model. These effects are most noticeable when VD is used for dual purposes.

Regional Difference of Causative Pollen in Children with Allergic Rhinitis.

The aim of this study was to investigate role of common pollen in Korean school-aged children with allergic rhinitis (AR) in 5 provinces (Incheon Metropolitan City-Gyeonggi Province, Chungcheongbuk-do, Gwangju Metropolitan City, Busan Metropolitan City, and Jeju Special Self-Governing Province), using a questionnaire and skin prick test, and to assess the differences among the residential regions. Among the enrolled 14,678 total children, 1,641 (22.0%) had AR. The sensitization rate to pollen (38.7%) was the second highest among examined allergens and significant differences were in the sensitization rates to trees, weeds, and grasses among the 5 provinces (P < 0.05). The sensitization to trees (25.2%) was the highest common among the pollen types and significant differences also were observed in the sensitization rates to alder, birch, Japanese cedar, oak, and elm among the 5 provinces. The sensitization rate to weeds (19.9%) was the second highest and significant differences were observed in the sensitization rate to Japanese hop, mugwort, and ragweed among the 5 provinces. The sensitization rate to house dust mite was 86.8%, the highest among examined allergens and that to Dermatophagoides farinae exhibited regional differences (P = 0.003) but not to D. farinae (P = 0.584). The sensitization rate to mold (13.5%) was the highest in Jeju and lowest in Busan, and a statistically significant difference was detected among the 5 provinces. These results support that examined pollen allergens are strongly associated with residential region due to regional causative pollen differences among children with AR within Korea to investigate the main pollen allergens.

The effect of Asian dust on asthma by socioeconomic status using national health insurance claims data in Korea.

CONTEXT: Asian dust events are associated with increased asthma incidence, asthma exacerbation, decreased lung function and increased risk for hospitalization. OBJECTIVE: The purpose of this study was to evaluate the effect of Asian dust events on asthma exacerbation by socioeconomic status using national health insurance claims data. MATERIALS AND METHODS: A case-crossover design was used to analyze asthma-related national health insurance claims, air pollutant and climate data from 2007 to 2013 in Seoul and Incheon, Korea. We stratified our analysis by socioeconomic status (health insurance versus medical aid subscribers) and calculated the maximum air pollutant levels and average climate values per day. The number of asthma-related visits to medical institutions per day was compared between "event" and "control" days. RESULTS: Compared with "control days", the average number of asthma-related visits to medical institutions decreased on "event" days and increased 1-5 d thereafter. The number of visits by health insurance subscribers also decreased on "event" days and increased 1-5 d thereafter, while the number of visits by medical aid subscribers did not change on "event" days but increased 1-4 d thereafter. DISCUSSION AND CONCLUSION: Our study confirms that Asian dust events result in an increased number of asthma-related visits to medical institutions. This effect differed by socioeconomic status.

Humidifier disinfectant-associated children's interstitial lung disease.

RATIONALE: Beginning in 2006, epidemics of a fatal lung injury of unknown cause in children were observed in Korea every spring. A recent study demonstrated that this type of children's interstitial lung disease (chILD) is associated with humidifier disinfectant use. OBJECTIVES: To determine the clinical characteristics of this type of chILD and to assess whether the nationwide suspension of humidifier disinfectant sales in the autumn of 2011 affected its incidence. METHODS: The clinical characteristics of suspected cases between 2006 and 2011 were determined by a nationwide retrospective study. The potential causal relationship with humidifier disinfectants was examined by a prospective surveillance study after humidifier disinfectant sales were suspended. MEASUREMENTS AND MAIN RESULTS: In total, 138 children were diagnosed with this type of chILD, which was characterized by rapid progression, high mortality, predominance in the spring season, and a familial tendency. The annual incidence increased in 2011 and then dropped to zero in 2012. The children were on average 30.4 months old. The most frequent symptoms at admission were cough and dyspnea. As the disease progressed, the typical complication was spontaneous air leak. Eighty children (58%) died. Two years after humidifier disinfectant-sale suspension, no more new cases were found. CONCLUSIONS: This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.

Navigation Guided Biopsy Is as Effective as Frame-Based Stereotactic Biopsy.

BACKGROUND: Stereotactic biopsy is a standard procedure for brain biopsy. However, with advances in technology, navigation-guided brain biopsy has become a well-established alternative. Previous studies have shown that frameless stereotactic brain biopsy is as effective and safe as frame-based stereotactic brain biopsy is. In this study, the authors evaluate the diagnostic yield and complication rate of frameless intracranial biopsy. MATERIALS AND METHODS: We reviewed data from biopsy performed patients between March 2014 and April 2022. We retrospectively reviewed medical records, including imaging studies. Various intracerebral lesions were biopsied. Diagnostic yield and post-operative complications were compared with those of frame-based stereotactic biopsy. RESULTS: Forty-two frameless navigation-guided biopsy were performed, and the most common pathology was primary central nervous system lymphoma (35.7%), followed by glioblastoma (33.3%), and anaplastic astrocytomas (16.7%), respectively. The diagnostic yield was 100%. Post-operative intracerebral hematoma occurred in 2.4% of cases, but it was not symptomatic. Thirty patients underwent frame-based stereotactic biopsy, and the diagnostic yield was 96.7%. There was no difference in diagnostic rates between two methods (Fisher's exact test, p = 0.916). CONCLUSIONS: Frameless navigation-guided biopsy is as effective as frame-based stereotactic biopsy is, without causing further complications. We consider that frame-based stereotactic biopsy is no longer needed if frameless navigation-guided biopsy is used. A further study will be needed to generalize our results.

Clinicopathological significance and the associated signaling pathway of p21-activated kinase 1 (PAK1) in colorectal cancer.

The aim of this study was to evaluate the clinicopathological significance and associated signaling pathways of p21-activated kinase 1 (PAK1) in colorectal cancer (CRC). PAK1 immunohistochemical expression was investigated in 246 human CRC tissues to evaluate its clinicopathological significance and prognostic role. Correlations between PAK1 and the immunoscore, HIF-1α, and pFOXO1 were also evaluated. PAK1 was expressed in 169 of 246 CRC tissues (68.7%). PAK1 expression significantly correlated with the metastatic lymph node ratio (P = 0.023). However, PAK1 expression did not correlate with tumor size, tumor location, tumor differentiation, lymphovascular and perineural invasion, or distant metastasis. PAK1 expression was significantly higher in CRC with a low immunoscore than in CRC with a high immunoscore (P = 0.017). In addition, there were significant correlations between PAK1, HIF-1α, and pFOXO1 expression (P = 0.001 and P = 0.024, respectively). Patients with PAK1 expression had worse overall and recurrence-free survival than those without PAK1 expression (P 0.001 and P = 0.001, respectively). PAK1 expression was significantly correlated with worse prognosis in CRCs patients. In addition, PAK1 expression was significantly correlated with a low immunoscore and high expression of HIF-1α and pFOXO1 in CRCs.

Diagnostic Accuracy of ki-67 Labeling Index in Endoscopic Ultrasonography-Fine-Needle Aspiration Cytology and Biopsy of Pancreatic Neuroendocrine Neoplasms.

BACKGROUND: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. RESULTS: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. CONCLUSIONS: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

Epidemiology of patients with asthma in Korea: Analysis of the NHISS database 2006-2015.

Background: There has been a concerning increase in the prevalence and socioeconomic burden of asthma in Korea. Korea's National Health Insurance System (NHIS) covers insurance payment and claims management for all Koreans. Using National Health Insurance Sharing Service (NHISS) claims data. This study aimed to investigate patterns of healthcare utilization and direct cost in patients with asthma over a 10-year period. Methods: In this retrospective population-based study, we examined NHISS claims records between July 2005 and June 2016 and investigated healthcare utilization among patients with asthma based on age group and severity of disease (non-severe asthma [NSA] and severe asthma [SA]). Results: From 2006 to 2015, the total number of patients with asthma in Korea steadily increased from 743 968 to 2 286 309, with a corresponding increase in prevalence from 1.62% to 4.74%. The proportion of patients with SA decreased from 3.16% in 2006 to 1.56% in 2015; the proportion was consistently higher in men than in women. In addition, patients with SA had a higher cost per outpatient visit than patients with NSA, and the number of outpatient visits per year increased. The inhaled corticosteroid (ICS) prescription rate among patients with asthma decreased from 22.9% in 2006 to 15.7% in 2015. Furthermore, for a period of 10 years, more than 40% of patients with SA have been prescribed short-acting ß-2 agonists (SABAs). Conclusions: Although patients with SA comprised a small proportion of patients with asthma, they incurred greater medical costs per person. The pharmaceutical prescription pattern indicated a lack of ICS-based prescriptions and frequent SABA prescriptions.