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Objectives: We intended to determine the predictive factors of poor prognosis in cancer patients with chemotherapy-induced febrile neutropenia (FN).Methods: From January 1, 2007 to December 31, 2008, 396 episodes of FN in 346 cancer patients were retrospectively analyzed. Clinical and laboratory findings and Multinational Association of Supportive Care in Cancer (MASCC) risk-index score were analyzed and correlated with outcome.Results: Of the 396 episodes, 73 (18.4%) had serious medical complications including 15 (3.8%) deaths. There was significant difference between unfavorable and favorable outcomes in age, gender, hypotension, tachypnea, duration of fever ≤24 h before admission (44.4% vs. 61.3%), interval of ≤7 days since last chemotherapy (34.2% vs. 16.1%), and duration of neutropenia ≥4 days (34.2% vs. 15.8%; P < 0.05 each), as did C-reactive protein (CRP; 15.0 vs. 7.5 mg dL(-1)) and platelet count (66.4 × 10(3) vs. 123.7 × 10(3) mm(-3);P < 0.001 each). MASCC score was significantly lower in unfavorable outcomes than favorable outcomes (19.0 vs. 24.6, P < 0.001). However, prophylactic antibiotics, treatment with granulocyte colony-stimulating factor (G-CSF), and history of FN were not associated with outcome. On multivariate analysis, MASCC risk-index score (OR 23.2, 95% CI 10.48-51.37), tachypnea (OR 3.61, 95% CI 1.44-9.08), thrombocytopenia (OR 3.41, 95% CI 1.69-6.89), increased CRP (OR 3.23, 95% CI 1.62-6.45), and prolonged neutropenia (OR 2.52, 95% CI 1.21-5.25) were independent predictors of unfavorable outcomes.Conclusion: MASCC risk-index score <21, tachypnea, thrombocytopenia, increased CRP, and prolonged neutropenia may be strongly associated with poor outcomes in cancer patients with FN. [ABSTRACT FROM AUTHOR]

This study used ultrasonography to compare the thickness and cross-sectional area of the masticatory muscles in patients with temporomandibular joint arthralgia and investigated the differences according to sex and the co-occurrence of headache attributed to temporomandibular disorders (HATMD). The observational study comprised 100 consecutive patients with TMJ arthralgia (71 females and 29 males; mean age, 40.01 ± 17.67 years) divided into two groups: Group 1, including 86 patients with arthralgia alone (60 females; 41.15 ± 17.65 years); and Group 2, including 14 patients with concurrent arthralgia and HATMD (11 females; 33.00 ± 16.72 years). The diagnosis of TMJ arthralgia was based on the diagnostic criteria for temporomandibular disorders. The parameters of the masticatory muscles examined by ultrasonography were subjected to statistical analysis. The pain area (2.23 ± 1.75 vs. 5.79 ± 2.39, p-value = 0.002) and visual analog scale (VAS) score (3.41 ± 1.82 vs. 5.57 ± 12.14, p-value = 0.002) were significantly higher in Group 2 than in Group 1. Muscle thickness (12.58 ± 4.24 mm) and cross-sectional area (4.46 ± 2.57 cm 2 ) were larger in the masseter muscle than in the other three masticatory muscles (p-value < 0.001). When examining sex-based differences, the thickness and area of the masseter and lower temporalis muscles were significantly larger in males (all p-value < 0.05). The area of the masseter muscle (4.67 ± 2.69 vs. 3.18 ± 0.92, p-value = 0.004) and lower temporalis muscle (3.76 ± 0.95 vs. 3.21 ± 1.02, p-value = 0.049) was significantly smaller in Group 2 than in Group 1. An increase in VAS was significantly negatively correlated with the thickness of the masseter (r =  - 0.268) and lower temporalis (r =  - 0.215), and the cross-sectional area of the masseter (r =  - 0.329) and lower temporalis (r =  - 0.293). The masseter and lower temporalis muscles were significantly thinner in females than in males, and their volumes were smaller in patients with TMJ arthralgia and HATMD than in those with TMJ arthralgia alone. HATMD and decreased masseter and lower temporalis muscle volume were associated with increased pain intensity., (© 2024. The Author(s).)

To compare masticatory muscle thickness in patients with temporomandibular disorders (TMDs) during rest and clenching, and by body position, using ultrasonography. This prospective study included 96 patients with TMD (67 females, 29 males; mean age: 40.41 ± 17.88 years): group 1, comprising 66 patients with TMD without bruxism (TMD&#95;nonbruxer), and group 2, comprising 30 patients with concurrent TMD and bruxism (TMD&#95;bruxer). In patients with TMD, bruxism was correlated with the presence of tinnitus, muscle stiffness, sleep problems, psychological stress, and restricted mouth opening. The masseter muscle significantly thickened during clenching (11.16 ± 3.03 mm vs 14.04 ± 3.47 mm, p < 0.001), whereas the temporalis muscle showed no significant increase in thickness from resting to clenching in an upright position (7.91 ± 1.98 vs 8.39 ± 2.08, p = 0.103). Similarly, during clenching in the supine position, the masseter muscle was significantly thicker compared with rest (11.24 ± 2.42 vs 13.49 ± 3.09, p < 0.001), but no significant difference was observed in temporal muscle thickness (8.21 ± 2.16 vs 8.43 ± 1.94, p = 0.464). In comparison between two groups, the average thickness of the masseter muscle was greater among TMD&#95;bruxers than among TMD&#95;nonbruxers in both the upright and supine positions (all p < 0.05). In the generalized lineal model, female sex (B = - 1.018, 95% confidence interval [CI] - 1.855 to - 0.181, p = 0.017) and bruxism (B = 0.868, 95% CI 0.567 to 1.169, p = 0.048) significantly predicted changes in masseter muscle thickness. Female sex (B = - 0.201, 95% CI - 0.299 to - 0.103, p = 0.011), increased age (B = - 0.003, 95% CI - 0.005 to 0.000, p = 0.038), and muscle stiffness (B = - 1.373, 95% CI - 2.369 to - 0.376, p = 0.007) were linked to decreased temporal muscle thickness. Comparing TMD nonbruxer and bruxer muscle thicknesses in upright and supine positions revealed significant increased thickness in the masseter muscle during clenching but not in the temporalis muscle. Masseter muscle thickness varied significantly by sex, body position, and resting/clenching, notably influenced by bruxism. These findings emphasize the relevance of these factors in clinical examinations of patients with TMD., (© 2024. The Author(s).)

Purpose: This study aimed to propose a revision of the evaluation objectives of the Korean Dentist Clinical Skill Test by analyzing the opinions of those involved in the examination after a review of those objectives., Methods: The clinical skill test objectives were reviewed based on the national-level dental practitioner competencies, dental school educational competencies, and the third dental practitioner job analysis. Current and former examinees were surveyed about their perceptions of the evaluation objectives. The validity of 22 evaluation objectives and overlapping perceptions based on area of specialty were surveyed on a 5-point Likert scale by professors who participated in the clinical skill test and dental school faculty members. Additionally, focus group interviews were conducted with experts on the examination., Results: It was necessary to consider including competency assessments for “emergency rescue skills” and “planning and performing prosthetic treatment.” There were no significant differences between current and former examinees in their perceptions of the clinical skill test’s objectives. The professors who participated in the examination and dental school faculty members recognized that most of the objectives were valid. However, some responses stated that “oromaxillofacial cranial nerve examination,” “temporomandibular disorder palpation test,” and “space management for primary and mixed dentition” were unfeasible evaluation objectives and overlapped with dental specialty areas., Conclusion: When revising the Korean Dentist Clinical Skill Test’s objectives, it is advisable to consider incorporating competency assessments related to “emergency rescue skills” and “planning and performing prosthetic treatment.”

Peptide and protein drugs, such as epidermal growth factor (EGF), face challenges related to stability and bioavailability. Recently, hydrogels have emerged as promising carriers for these drugs. This study focuses on a light-responsive hydrogel-based drug delivery system for the controlled release of EGF in wound healing. A photocleavable (PC) linker was designed to bind EGF to the hydrogel matrix, enabling UV light-triggered release of EGF. Hydrogels have evolved from drug reservoirs to controlled release systems, and the o-nitrobenzyl-based PC linkers offer selective cleavage under UV irradiation. We used a thiol-ene crosslinked hyaluronic acid (HA) hydrogel matrix modified with the PC-linked EGF. The release of EGF from the HA hydrogel under UV irradiation was evaluated, along with in vitro and in vivo experiments to assess the controlled effect of EGF on wound healing. Our results indicate that the successful development of a light-responsive hydrogel-based system for precise temporal release of EGF enhances the therapeutic potential in wound healing. This study highlights the importance of incorporating stimulus-responsive functionalities into hydrogel-based drug delivery systems to optimize protein drugs in clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.

We report on a scalable and programmable integrated Mach-Zehnder interferometer (MZI) with a tunable free spectral range (FSR) and extinction ratio (ER). For the tunable path of the MZI, we designed and utilized a tunable delay line having high flexibility based on silicon photonic microelectromechanical systems (MEMS). By utilizing MEMS, the length of the delay line can be geometrically modified. In this way, there is no optical loss penalty other than the waveguide propagation loss as the number of tunable steps increases. Therefore, our device is more scalable in terms of optical loss than the previous approaches based on cascaded MZIs. In addition, the tuning energy required to reconfigure the length is only 8.46 pJ.

Background: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in the pediatric population. Microglia and infiltrating monocyte-derived macrophages are crucial immune cells that modulate the neuroinflammatory response following TBI. Using C34, a novel pharmacologic toll-like receptor 4 inhibitor, we investigated the intricate interactions between these cells in a murine TBI model., Methods: A murine controlled cortical impact model was used, and the results were analyzed on postinjury days 1, 7, 28, and 35. The experimental groups are as follows: (1) sham C57BL/6 wild-type (WT), (2) TBI WT, (3) sham WT + C34, and (4) TBI WT + C34. Quantitative real-time polymerase chain reaction was used to quantify gene expression associated with microglial activation, apoptotic pathways, and type 1 interferon pathway. Flow cytometry was used to isolate microglia and infiltrating monocytes. Brain lesion volumes were assessed using magnetic resonance imaging. Last, neurocognitive outcomes were evaluated using the Morris Water Maze test. Student's t test and one-way analysis of variance were used for statistical analysis with significance achieved when p < 0.05., Results: Toll-like receptor 4 inhibition leads to improved neurological sequela post-TBI, possibly because of an increase in infiltrating anti-inflammatory monocytes and a decrease in IFN regulatory factor 7 during acute inflammation, followed by a reduction in apoptosis and M2 microglial expression during chronic inflammation., Conclusion: Toll-like receptor 4 inhibition with C34 skews infiltrating monocytes toward an anti-inflammatory phenotype, leading to enhanced neurocognitive outcomes. Moreover, although M2 microglia have been consistently shown as inducers of neuroprotection, our results clearly demonstrate their detrimental role during the chronic phases of healing post-TBI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We investigated the association between cataract and allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma using 2,631,015 subjects' data from the 2009 National Health Insurance Service-Health Screening Cohort in Korea. Each allergic disease was defined as three or more occasions of diagnosis within 1 year with dedicated ICD-10 codes. The primary endpoint was newly received cataract surgery during the follow-up period. In total, 447,883 subjects had at least one allergic disease. During the mean follow-up of 7.8 ± 1.7 years, newly developed cataract surgery was observed in 301,693 subjects (allergic group, n = 69,321; non-allergic group, n = 232,372). After adjusting for demographic characteristics (age, sex), systemic and ocular comorbidities, socioeconomic status, and lifestyle factors (smoking, drinking, regular exercise), the allergic group had a higher hazard ratio (HR) for cataract development compared with the non-allergic group. We further performed a subgroup analysis for patients regarding sex and age. In the subgroup analysis of subjects with AD, men aged < 50 years had a higher HR compared to women of the same age group. In conclusion, subjects with allergic diseases had a higher risk of cataract surgery than their counterparts, and the combination of AD and AR resulted in the highest risk. Particularly, the association was more evident in male than female patients with AD aged < 50 years., (© 2022. The Author(s).)

Background: Acute urticaria is a common cutaneous disease encountered in children, while anaphylaxis can show cutaneous symptoms as well as systemic symptoms. One study found that urticaria tends to precede anaphylaxis, but studies on the different role of eosinophils and related cytokines in anaphylaxis and urticaria are lacking., Objective: The aim of this study was to compare the clinical features, total eosinophil count, serum levels of interleukin (IL)-18, IL-18 binding protein (BP), IL-1 receptor-like (RL) 1, and IL-33 and compare with tryptase to examine if any differences could be found between patients who experienced anaphylaxis and urticaria., Methods: We included 63 patients with urticaria and 52 patients with anaphylaxis. We measured total eosinophil count and the serum levels of total IgE, tryptase, IL-18, IL-18BP, IL-1RL1, and IL-33, and we compared the differences between the groups. Lastly, receiver operating characteristic curves were constructed to determine which factors accurately diagnosed anaphylaxis., Results: No significant differences were observed in the clinical characteristics or sensitization between urticaria group and anaphylaxis group. Laboratory findings showed that total eosinophil count and IL-18BP were significantly lower in the anaphylaxis group, compared with the urticaria group. IL-18BP showed significant correlation with tryptase. The receiver operating characteristic curve for IL-18BP for diagnosing anaphylaxis had an area under the curve of 0.530., Conclusions: IL-18BP level was significantly different in patients with anaphylaxis compared to those with urticaria. Serum IL-18BP level may be used to differentiate between the patients with urticaria or anaphylaxis.

Background: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits., Methods: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic., Results: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001)., Conclusions: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective., (© 2021 Japan Pediatric Society.)

The available treatment options include corneal transplantation for significant corneal defects and opacity. However, shortage of donor corneas and safety issues in performing corneal transplantation are the main limitations. Accordingly, we adopted the injectable in situ-forming hydrogels of collagen type I crosslinked via multifunctional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) for treatment and evaluated in vivo biocompatibility. The New Zealand White rabbits (N = 20) were randomly grouped into the keratectomy-only and keratectomy with PEG-collagen hydrogel-treated groups. Samples were processed for immunohistochemical evaluation. In both clinical and histologic observations, epithelial cells were able to migrate and form multilayers over the PEG-collagen hydrogels at the site of the corneal stromal defect. There was no evidence of inflammatory or immunological reactions or increased IOP for PEG-collagen hydrogel-treated corneas during the four weeks of observation. Immunohistochemistry revealed the presence of α-smooth muscle actin (α-SMA) in the superior corneal stroma of the keratectomy-only group (indicative of fibrotic healing), whereas low stromal α-SMA expression was detected in the keratectomy with PEG-collagen hydrogel-treated group. Taken together, we suggest that PEG-collagen may be used as a safe and effective alternative in treating corneal defect in clinical setting., (© 2021. The Author(s).)

The revolution in genetics has rapidly increased our knowledge of human and mouse genes that are critical for the formation of dental enamel and helps us understand how enamel evolved. In this graphical review we focus on the roles of 41 genes that are essential for the secretory stage of amelogenesis when characteristic enamel mineral ribbons initiate on dentin and elongate to expand the enamel layer to the future surface of the tooth. Based upon ultrastructural analyses of genetically modified mice, we propose a molecular model explaining how a cell attachment apparatus including collagen 17, α6ß4 and αvß6 integrins, laminin 332, and secreted enamel proteins could attach to individual enamel mineral ribbons and mold their cross-sectional dimensions as they simultaneously elongate and orient them in the direction of the retrograde movement of the ameloblast membrane., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to analyse age-related anatomical changes in teeth and mandibular structures using panoramic radiographs., Materials and Methods: We included 471 subjects aged 13-70 years (mean, 35.12 ± 18.72 years). Panoramic radiographs were used to record intraoral condition and radiomorphometric parameters. After grouping the subjects by age decade, descriptive statistics and analysis of variance were performed to assess age-related patterns., Results: The number of missing teeth, endodontically treated teeth, full veneer crowns, and implant prosthesis increased with age (all p < .05). The prevalence of periodontitis significantly increased after the 40s and was the highest in the 60s (57.1%). The maxillary canine root was the longest in the 10s and 20s (p < .001). With age, the mandibular canal and mental foramen moved towards the alveolar bone crest, on the opposite side of the mandibular inferior border. The pulp area and pulp-to-tooth ratio of maxillary/mandibular first molars were significantly higher in the 10s and 20s than in other age groups (all p < .05)., Conclusions: We provided comprehensive information on age-related anatomical changes in teeth and mandibular structures based on panoramic radiographs. Various radiographic parameters showed specific changes with increasing age. Assessing these age-related changes can be useful in determining an individual's age, and may aid in medico-legal and forensic judgments., (© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Background/purpose: Differences exist among racial and ethnic groups in the prevalence and severity of allergic diseases. However, influence of population admixing on allergic disease has not been studied. We examined the effect of population admixing on the occurrence of allergic disease., Methods: We reviewed the data of 68,043 adolescents who participated in the 11th Korea Youth Risk Behavior Web-based Survey, which provides a sample that is representative of the entire Korean middle school and high school student population. Multi-ethnic status was determined by using parental country of birth and prevalence of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) was determined by questionnaire., Results: Multi-ethnic adolescents accounted for approximately 0.9% of the total adolescents. Prevalence of asthma was significantly higher in multi-ethnic group than non multi-ethnic group while that of AR and AD was significantly higher in non multi-ethnic group than multi-ethnic group. Parental region of country at birth showed a significant difference in prevalence of allergic disease. Univariate analysis found that urbanity, perceived economic status (PES), parental region of country at birth, and environmental tobacco smoke (ETS) showed a significant odds ratio (OR) in asthma, AR, and AD. Body mass index (BMI) showed a significant OR in asthma and AD. After adjusting for urbanity, PES, BMI and ETS, multiethnicity showed significantly lower OR in AR and AD., Conclusion: Population admixing appears to have significant effect on the prevalence of allergic disease. Further study will be needed to clarify the effect of population admixing on prevalence of allergic disease., (Copyright © 2018. Published by Elsevier B.V.)

Background: Ameloblastin (AMBN) is a secreted matrix protein that is critical for the formation of dental enamel and is enamel-specific with respect to its essential functions. Biallelic AMBN defects cause non-syndromic autosomal recessive amelogenesis imperfecta. Homozygous Ambn mutant mice expressing an internally truncated AMBN protein deposit only a soft mineral crust on the surface of dentin., Methods: We characterized a family with hypoplastic amelogenesis imperfecta caused by AMBN compound heterozygous mutations (c.1061T>C; p.Leu354Pro/ c.1340C>T; p.Pro447Leu). We generated and characterized Ambn knockout/NLS-lacZ (Ambn lacZ/lacZ ) knockin mice., Results: No AMBN protein was detected using immunohistochemistry in null mice. ß-galactosidase activity was specific for ameloblasts in incisors and molars, and islands of cells along developing molar roots. Ambn lacZ/lacZ 7-week incisors and unerupted (D14) first molars showed extreme enamel surface roughness. No abnormalities were observed in dentin mineralization or in nondental tissues. Ameloblasts in the Ambn lacZ/lacZ mice were unable to initiate appositional growth and started to degenerate and deposit ectopic mineral. No layer of initial enamel ribbons formed in the Ambn lacZ/lacZ mice, but pockets of amelogenin accumulated on the dentin surface along the ameloblast distal membrane and within the enamel organ epithelia (EOE). NLS-lacZ signal was positive in the epididymis and nasal epithelium, but negative in ovary, oviduct, uterus, prostate, seminal vesicles, testis, submandibular salivary gland, kidney, liver, bladder, and bone, even after 15 hr of incubation with X-gal., Conclusions: Ameloblastin is critical for the initiation of enamel ribbon formation, and its absence results in pathological mineralization within the enamel organ epithelia., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

The study aims to evaluate whether bone scintigraphy is effective in diagnosing temporomandibular joint (TMJ) osteoarthritis (OA) in juvenile patients. A retrospective study was conducted with 356 consecutive patients with TMJ-OA who were clinically assessed according to the Research Diagnostic Criteria for Temporomandibular Disorders. Patients were assigned to three groups based on their ages: Group 1: aged 12-16 years; Group 2: aged 17-19 years; and Group 3: aged 20 years. Additionally, we performed qualitative and quantitative analyses of bone scintigraphy images for the TMJ uptake ratio of the involved joint. The diagnostic rate of TMJ-OA ( n  = 356, 100%), and the overall presence of subjective pain ( n  = 282, 77.3%) was closest to the results of bone scintigraphy ( n = 333, 91.2%). In addition, reported TMJ pain was significantly associated only with the results of bone scintigraphy and not with the results of panoramic radiography or cone beam computed tomography (CBCT) in all age groups. With CBCT as the reference standard, the optimal cutoff values of the uptake ratio for the diagnosis of TMJ-OA were 2.171 and 2.017 in Groups 1 and 2, respectively ( P value < 0.05). Our results suggest that bone scintigraphy can be considered a useful modality for diagnosing TMJ-OA in juvenile patients., Competing Interests: The authors declare no conflicts of interest.

Background: The aim of this study is to determine whether there is correlation between endothelial function and skeletal muscle function measured by hand grip strength in elderly women., Methods: This cross-sectional study used data of NAMGARAM-2 cohort. The NAMGARAM-2 cohort consisted of a group of people living in three rural communities. They were enrolled for studies on activity limitation due to age-related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. They were residents aged 40 years or older. They agreed to participate in this cohort from March 2016 to May 2017. Peripheral endothelial function was assessed by reactive hyperaemia-peripheral arterial tonometry using EndoPAT2000 system. Hand grip strength was measured using a digital hand dynamometer., Results: Endothelial function index assessed by EndoPAT was worse in the low grip strength group than that in the normal group of elderly women (1.54 ± 0.51 in the low grip strength group vs. 1.77 ± 0.67 in the normal group, P = 0.003). There was a positive correlation between hand grip strength and endothelial function (r = 0.176, P = 0.007). On stepwise multivariate analysis, endothelial dysfunction (reactive hyperaemia-peripheral arterial tonometry index < 1.67) significantly increased the risk of low hand grip strength (odds ratio = 2.019; 95% confidence interval = 1.107-3.682; P = 0.022)., Conclusions: Endothelial function and skeletal muscle strength had a significant correlation in elderly women, providing additional support for the relevant role of vascular system in sarcopenia., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: Ultraviolet-B (UVB) light exposure is the major risk factor for developing a pterygium, and serum 25-hydroxyvitamin D (25(OH)D) level is an objective measure of UVB light exposure. In this study, we investigated the association between pterygium, sun exposure, and serum 25(OH)D., Methods: This population-based, cross-sectional study comprised 12,258 adults (aged ≥19 years) participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2012. The enrolled subjects underwent interviews, clinical examinations, and laboratory investigations. The serum 25(OH)D levels were measured, and pterygium was examined by using a slit lamp. We used three adjusted logistic regression models and selected covariates as potential confounders., Results: The overall prevalence of pterygium was 7.09, and 53.1% of these subjects were women. The prevalence of pterygium was higher in elderly subjects and those who lived at low latitudes. In multivariate analysis with adjustment for confounding factors, subjects with a serum 25(OH)D level > 30 ng/mL, 25-30 ng/mL, and 15-20 ng/mL had an odds ratio (OR) (95% confidence interval [CI]) of 1.565 (1.035-2.366), 1.545 (1.086-2.198), 1.8 (1.358-2.386), and 1.535 (1.216-1.938), respectively, compared to those with a serum 25(OH)D level < 15 ng/mL. Subjects with a daily sun exposure > 5 h had an OR (95% CI) of 1.761 (1.395-2.223) compared to subjects with a daily sun exposure < 2 h., Conclusion: The present study provides epidemiological evidence of an association of daily sun exposure and serum 25(OH)D levels with pterygium in a representative Korean population.

Purpose: Dry eye disease (DED) of ocular graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT). Ongoing inflammation and irreversible fibrotic changes of the ocular surface and adnexa are obstacles for effective treatment of ocular GVHD. We hypothesized that topical cyclosporine A (CsA) pretreatment might be effective in preventing ocular GVHD., Methods: In this prospective, randomized, comparative study, patients were randomly assigned to the topical CsA treatment (4 times daily in both eyes for a month before allogeneic HSCT and continued use of eye drops after transplantation) or control (no treatment) groups. Participants underwent thorough ophthalmic examination-including Ocular Surface Disease Index questionnaire survey, Schirmer test, tear break-up time (TBUT) evaluation, and corneal fluorescein staining-before and 1, 2, and 3 months after allogeneic HSCT., Results: Fifty-eight participants completed the study. Among patients with baseline Schirmer values <10 mm and TBUT <5 s before allogenic HSCT, those in the topical CsA treatment group exhibited significantly better corresponding values after transplantation than patients in the control group., Conclusions: Topical CsA pretreatment might be beneficial in the early stage of DED and might prevent further inflammation and consequent irreversible fibrosis, especially in patients with preexisting DED components.

Background: Left lateral mitral isthmus (LLMI) linear ablation is a safe and effective technique for treating left mitral flutter. LLMI linear ablation with pulmonary vein isolation may reduce the recurrence of persistent atrial fibrillation. However, epicardial ablation within the coronary sinus (CS) is often required to create the LLMI block line. If the necessity for epicardial ablation is checked before ablation, complications may be reduced., Methods: We recruited 135 patients who underwent their first LLMI ablation and divided them into two groups, one group not requiring epicardial ablation for creating a conduction block at the LLMI (Endo group) and another requiring it (Epi group). These two groups were compared in terms of the electrogram characteristics of the CS., Results: Bidirectional block through the LLMI was achieved in 94.8% of patients. In 42% of these patients, not only the endocardium but also the epicardium was ablated. As for the electrogram, the Endo group had lower atrium voltage and atrioventricular voltage ratios (p = 0.009) than the Epi group before LLMI ablation. By contrast, there were no significant differences in the atrium voltage and the atrioventricular voltage ratio between these two groups after LLMI ablation., Conclusions: For creating a conduction block at the LLMI, the atrium voltage and the atrioventricular voltage ratio in the CS before ablation are important. The atrioventricular voltage ratio is a crucial criterion for determining whether epicardial ablation is necessary; furthermore, the atrioventricular voltage ratio in the CS must be reduced with or without epicardial ablation.

Background: Metabolic syndrome and dyslipidemia contribute to the development of a pro-inflammatory state in asthma. However, studies investigating the association between asthma and dyslipidemia have reported conflicting results. This study aimed to uncover the relationship between asthma and lipid profiles in adolescents using a national health and nutrition survey., Methods: This cross-sectional study analyzed the 2010-2012 Korea National Health and Nutrition Examination Survey data and included 2841 subjects aged 11-18 years with fasting blood sample data. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed. We compared asthma prevalence between high-risk and low-risk lipid groups., Results: There were 123 adolescents with asthma and 2718 without asthma (controls). The TC/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C levels were significantly higher in the asthma group than in the non-asthma group (P < 0.05). The high-risk groups displayed significantly higher asthma prevalence with higher TC, TG, LDL-C, and non-HDL-C levels and TG/HDL-C ratio than the low-risk groups (P < 0.05). After adjusting for potential confounding factors, the high-risk groups were associated with asthma according to their higher TC levels (adjusted odds ratio, 1.69; 95% confidence interval, 1.012-2.822) and TG/HDL-C ratios (adjusted odds ratio, 1.665; 95% confidence interval, 1.006-2.756)., Conclusions: Asthma prevalence was greater in adolescents with a high TC level and TG/HDL-C ratio. In addition to the standard lipid profile, elevated TG/HDL-C ratio can be used as a useful additional lipid measure to evaluate interactions between dyslipidemia and asthma.

Background: We aimed to compare the antipyretic efficacy, safety, and tolerability between oral dexibuprofen and intravenous propacetamol in children with upper respiratory tract infection (URTI) presenting with fever., Methods: Patients aging from 6 months to 14 years admitted for URTI with axillary body temperature ≥ 38.0 °C were enrolled and randomized into the study or control group. Patients in the study group were intravenously infused with propacetamol and subsequently oral placebo medication was administered. Patients in the control group were intravenously infused with 100 mL of 0.9% sodium chloride solution without propacetamol and then oral dexibuprofen was administered. We checked the body temperature of all patients at 0.5 h (hr), 1 h, 1.5 h, 2 h, 3 h, 4 h, and 6 h after oral placebo or dexibuprofen had been applied., Results: A total of 263 patients (125 in the study group) were finally enrolled. The body temperatures of patients in the study group were significantly lower until 2 h after administration (37.73 ± 0.58 vs 38.36 ± 0.69 °C (p < 0.001), 37.37 ± 0.53 vs 37.88 ± 0.69 °C (p < 0.001), 37.27 ± 0.60 vs 37.62 ± 0.66 °C (p < 0.001), 37.25 ± 0.62 vs 37.40 ± 0.60 °C (p = 0.0452), at 0.5 h, 1 h, 1.5 h, and 2 h, respectively). The two groups showed no significant differences in terms of the range of body temperature decrease, the Area Under the Curve of body temperature change for antipyretic administration-and-time relationship, the maximum value of body temperature decrease during the 6 h test period, the number of patients whose body temperature normalized (< 37.0 °C), the mean time when first normalization of body temperature, and the development of adverse events including gastrointestinal problem, elevated liver enzyme, and thrombocytopenia., Conclusions: Intravenous propacetamol may be a safe and effective choice for pediatric URTI patients presenting with fever who are not able to take oral medications or need faster fever control., Trial Registration: CRIS KCT0002888 . Date of registration: July 31st, 2013.

Objectives: Aspiration of foreign bodies into the tracheobronchial tree is a common accident in children. This study aimed to evaluate the safety and outcome of foreign body removal by flexible bronchoscopy using a retrieval basket in children., Methods: This was a retrospective study of children treated for foreign bodies in the airway via flexible bronchoscopy using a retrieval basket at a tertiary hospital in Korea between February 2014 and October 2017. The medical records of the patients were retrospectively reviewed and analyzed., Results: A total of 20 children underwent foreign body removal from the airway via flexible bronchoscopy using a retrieval basket. The median age of the patients was 16 (range, 10-21.5) months, and 12 (60%) were male. Foreign bodies removed included 16 (80%) organic items including peanuts, almond, and beans, and 4 (20%) inorganic items including a plastic bag, metal screw, spring, and Lego brick. The locations of the foreign bodies included the central airway ( n = 5; trachea, n = 4; subglottic area, n = 1), right bronchial tree ( n = 9), and left bronchial tree ( n = 6). Successful removal was observed in 18 (90%) cases. The only complication that occurred was mild laryngeal edema ( n = 2) after the procedure; both improved with corticosteroid administration., Conclusion: Flexible bronchoscopic extraction of a foreign body in the airway using a retrieval basket in children can be performed successfully with minimal complications., Competing Interests: There are no conflicts of interest.

Objectives: Lidocaine, a local anaesthetic is a treatment option in uncontrolled asthma due to its immunomodulatory effects. In the present study, proparacaine (PPC), a derivative of lidocaine was examined for its therapeutic application in a mouse model of allergic rhinitis., Methods: The mice were grouped into 4 groups: control group, allergic rhinitis (AR) group, ciclesonide (CIC) group, and PPC group. Nasal symptom scores, eosinophil counts, goblet cell counts, and mast cells counts in the nasal mucosa were measured. Serum ovalbumin (OVA)-specific immunoglobulin (Ig) E, OVA-specific IgG1, OVA-specific IgG2a, interleukin (IL)-4, IL-5, and cortisol levels were measured., Results: Intranasal administration of PPC significantly decreased nasal symptoms, number of eosinophils, goblet cells, and mast cells in the lamina propria of the nasal mucosa. Serum OVA-specific IgE, OVA-specific IgG1, OVA-specific IgG2a was significantly higher in the AR compared with the control group. Serum level of IL-4 was significantly lower in the CIC group and PPC group in comparison with AR group. Serum IL-5 showed no significant difference among all groups. No significant difference in serum cortisol levels was observed among the 4 groups., Conclusion: PPC appears to have a therapeutic potential in treatment of allergic rhinitis in a mouse model by reducing eosinophil, goblet cell, and mast cell infiltration in the nasal mucosa.

Background: The clinical characteristics and outcomes of asymptomatic patients with paroxysmal or persistent/permanent atrial fibrillation (AF) are largely unknown., Methods: The Fushimi AF Registry is a community-based prospective survey of patients with AF who visited the participating medical institutions in Fushimi-ku, Japan. We investigated the clinical characteristics and outcomes of asymptomatic vs symptomatic patients in the paroxysmal AF (PAF; n = 1,837) and persistent/permanent (sustained atrial fibrillation [SAF]; n = 1,912) subgroups., Results: In the PAF group, asymptomatic patients were older (asymptomatic vs symptomatic group, 74.1 vs 71.1 years of age; P < .01), more often male (62.1% vs 55.6%; P < .01), and had a higher CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, history of stroke, vascular disease, age 65-74 years, and female sex) score (mean, 3.37 ± 1.73 vs 2.99 ± 1.63; P < .01), whereas the prevalence of major co-morbidities and CHA 2 DS 2 -VASc scores were comparable in the SAF group. Multivariable analysis indicated that age (≥ 75 years), history of stroke/systemic embolism, male sex, and chronic kidney disease were independent determinants of asymptomatic status in the PAF group, whereas age was nonsignificant in the SAF group. During the follow-up period, all-cause mortality was significantly higher (hazard ratio, 1.71 [95% CI, 1.31-2.29]; P < .01) in asymptomatic patients compared with symptomatic patients in the PAF group, whereas it was comparable in the SAF group., Conclusions: Asymptomatic clinical status is associated with older age, male sex, more co-morbidities with a higher stroke risk profile, and a higher incidence of all-cause death in patients with PAF; these characteristics and outcomes were not seen in the SAF group., Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000005834; URL: www.umin.ac.jp/ctr/index.htm., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Eosinophils are encountered in many skin diseases, but the role of eosinophils in atopic dermatitis (AD) remains uncertain., Objective: To examine the role of serum eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and total IgE as a biomarker of disease severity and relapse in severe recalcitrant AD., Methods: We enrolled 99 patients with AD: 37 with severe recalcitrant AD, 20 with severe AD, and 42 with mild to moderate AD. We examined the difference in serum level of total IgE, ECP, and EDN between the groups and whether any correlation existed between disease severity and ECP or EDN. Lastly, difference in levels of ECP or EDN between those who experienced relapse was examined in the severe recalcitrant group., Results: Serum levels of total IgE, ECP, and EDN were significantly higher in the severe recalcitrant AD group and severe AD group compared with the mild to moderate AD group. No significant difference was found in serum levels of total IgE, ECP, and EDN between the severe recalcitrant group and severe group. EDN had a significant positive correlation with the SCORing Atopic Dermatitis. No significant correlation was found between EDN and ECP. In the severe recalcitrant group, 29.7% of patients experienced relapse, and EDN was significantly higher in those who experienced relapse. The cutoff value of EDN for predicting relapse was 64.5., Conclusion: EDN correlated with the disease severity of AD. EDN may predict relapse in severe recalcitrant AD. The EDN serum level could be considered a candidate molecule as a clinical biomarker for evaluating AD disease activity and a predictor of relapse., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Hypertension is considered a major risk factor of stroke and systemic embolism (SE) as well as bleeding in patients with atrial fibrillation (AF). The purpose of this study was to investigate the relationship of hypertension and systolic blood pressure (SBP) with the risk of stroke/SE or bleeding in AF patients., Methods: The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000. Follow-up data were available for 3,713 patients (follow-up rate 90.0%) as of August 2015, and the median follow-up period was 1,035 days., Results: We compared the clinical backgrounds at baseline, and follow-up outcomes of AF patients between those with hypertension (HTN; n = 2,304, 62.1% of total) and those without (non-HTN; n = 1,409). History of hypertension was neither associated with the incidence of stroke/SE, ischemic stroke, hemorrhagic stroke nor major bleeding. However, when we divided the HTN group by baseline SBP ≥150 mm Hg (HTN-high blood pressure [HBP]: n = 305, 13.3% of HTN group) or <150 mm Hg (HTN-low blood pressure [LBP]: n = 1,983), HTN-HBP group was significantly associated with a higher incidence of both stroke/SE (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.08-2.72) and major bleeding (HR: 2.01, 95% CI: 1.21-3.23) compared with the non-HTN group. In contrast, HTN-LBP group was not associated with the risk of stroke/SE or major bleeding, compared with the non-HTN group., Conclusion: The incidences of stroke/SE and bleeding were higher in AF and hypertension patients with elevated SBP. UMIN Clinical Trials Registry: UMIN000005834., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Female sex is considered a risk factor for thromboembolism in patients with atrial fibrillation (AF), and is included in the risk stratification scheme, CHA 2 DS 2 -VASc score. The purpose of the present study was to investigate the clinical outcomes of female Japanese AF patients.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto. Follow-up data were available for 3,878 patients. Female AF patients (n=1,551, 40.0%) were older (77.0 vs. 71.4 years; P<0.001) than male patients (n=2,327, 60.0%). Female patients were more likely to have heart failure (31.1% vs. 23.7%; P<0.001). Previous stroke incidence (19.2% vs. 21.4%; P=0.083) was comparable between male and female patients. During the median follow-up period of 1,102 days, Cox regression analysis demonstrated that female sex was not independently associated with a risk of stroke or systemic embolism (adjusted hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.54-1.00, P=0.051). However, female sex showed an association with a lower risk of intracranial hemorrhage (adjusted HR 0.54; 95% CI: 0.30-0.95, P=0.032) and all-cause death (adjusted HR 0.56; 95% CI: 0.46-0.68, P<0.001)., Conclusions: We demonstrated that female sex is not independently associated with an increased risk of thromboembolism, but is associated with a decreased risk of intracranial hemorrhage and all-cause death in Japanese AF patients enrolled in the Fushimi AF Registry.

Background: The current status and outcomes of direct oral anticoagulant (DOAC) use have not been widely evaluated in unselected patients with atrial fibrillation (AF) in the real world.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions (n=80) in Fushimi, Kyoto, Japan. Follow-up data with oral anticoagulant (OAC) status were available for 3,731 patients by the end of November 2015. We evaluated OAC status and clinical outcomes according to OAC status. The number (incidence rate) of stroke/systemic embolism (SE) and major bleeding events during the median follow-up of 3.0 years was 224 (2.3%/year) and 177 (1.8%/year), respectively. After the release of DOAC, the prevalence of DOAC use increased gradually and steadily, and that of warfarin, DOAC and no OAC was 37%, 26% and 36%, respectively in 2015. On Cox proportional hazards modeling incorporating change in OAC status as a time-dependent covariate for stroke/SE and major bleeding events, use of DOAC compared with warfarin was not associated with stroke/SE events (HR, 0.95; 95% CI: 0.59-1.51, P=0.82) or major bleeding events (HR, 0.82; 95% CI: 0.50-1.36, P=0.45)., Conclusions: In real-world clinical practice, there were no significant differences in stroke/SE events or major bleeding events for DOAC compared with warfarin in patients with AF.

Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region., (Copyright © 2017 Elsevier Inc. All rights reserved.)

PurposeTo investigate the association between urinary cotinine levels as an objective biological marker for exposure to nicotine and refractive status.Patients and methodsThis cross-sectional study analyzed data from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. A total of 1139 Korean adolescents aged 12-18 years were enrolled. Urinary cotinine concentrations and other potential risk factors for myopia were examined. Correlation analyses and multivariate regression analysis were performed to investigate the association between urinary cotinine level and refractive error.ResultsSpherical equivalent correlated significantly with urinary cotinine concentration (r=0.104, P=0.011). Lower urinary cotinine level was associated with a trend toward more myopic refractive errors (P for trend=0.003). After adjusting for age, sex, area of residence, physical activity, serum 25-hydroxyvitamin D level, parental income level, and receipt of basic livelihood security, subjects with a low urinary cotinine level had a significantly increased risk of myopia <-0.5 D (odds ratio (OR) 1.95, 95% confidence interval (CI) 1.18-3.21), <-3.0 D (OR 2.03, 95% CI 1.29-3.2), and <-6.0 D (OR 2.2, 95% CI, 1.15-4.23) when compared with subjects with a high urinary cotinine level. As urinary cotinine level decreased, the risks of myopia <-0.5 D, <-3.0 D, and <-6.0 D increased significantly (P for trend <0.05).ConclusionA trend toward less myopic refractive error was observed among Korean adolescents with higher urinary cotinine levels. This result provides the epidemiologic evidence implying nicotine as a potential modulator related with refractive development. Further studies with full consideration for myopia-associated risk factors are required to yield clear answers on the direct effect of smoking to the refractive status.

Background: Direct oral anticoagulants (DOACs) have been developed as alternatives to conventional therapy with warfarin for the treatment of acute venous thromboembolism (VTE) events. The safety and efficacy of DOACs in Japanese patients with acute VTE has been investigated in small trials or subgroups from global randomized controlled trials (RCTs)., Methods and Results: We conducted a systematic review and meta-analysis of RCTs, to compare the safety and efficacy of DOACs to those of conventional therapy in Japanese patients with acute VTE. Published research was systematically searched for RCTs that compared DOAC to conventional therapy in Japanese patients with acute VTE. Random-effects models were used to pool safety and efficacy data across RCTs. Three studies, including 386 patients, were identified. Patients randomized to DOAC had a decreased risk for all bleeding [risk ratio (RR) 0.69, 95% confidential interval (CI) 0.50-0.95], without any significant differences in recurrent VTE (RR 0.84, 95% CI 0.29-2.43) and recurrent VTE/all-cause death (RR 0.60, 95% CI 0.23-1.56)., Conclusion: DOACs offer clinical benefit over conventional therapy in Japanese patients with acute VTE, showing a significant difference in their bleeding profile., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Creatinine clearance (CrCl) has been widely used to adjust the dosage of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (AF) and exclude contraindicated patients. However, there are few available real-world data on the relation between CrCl and adverse clinical outcomes in patients with AF. Therefore, we evaluated the clinical characteristics and adverse events in Japanese patients with AF stratified by CrCl. We categorized patients in the Fushimi AF Registry, a large prospective community-based Japanese cohort of patients with AF, into 3 groups as follows: (1) CrCl <30 ml/min, (2) CrCl 30 to 49 ml/min, and (3) CrCl ≥50 ml/min. We evaluated 3,080 patients after a median follow-up of 1,076 days. Comparing with patients with CrCl ≥50 ml/min, patients with AF with CrCl <30 ml/min showed increased risks of stroke/systemic embolism (SE) (hazard ratio [HR] 1.68; 95% confidence interval [CI] 1.04 to 2.65; p = 0.04) and major bleeding (HR, 2.08; 95% CI 1.23 to 3.39; p = 0.008) after adjustment for prespecified factors. Patients with AF with CrCl <30 ml/min were also associated with higher risks of all-cause death, hospitalization for heart failure, myocardial infarction, or the composite of all-cause death and stroke/SE. However, no excess risk of stroke/SE (HR 1.10; 95% CI 0.76 to 1.58; p = 0.6) or major bleeding (HR 0.98; 95% CI 0.63 to 1.48; p = 0.9) was noted for patients with CrCl 30 to 49 ml/min. In conclusion, Japanese patients with AF with CrCl <30 ml/min were closely associated with adverse clinical events including stroke/SE and major bleeding., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/purpose: Activation of cell surface CD30 by immobilized anti-CD30 monoclonal antibodies (mAb) induces strong apoptosis in human eosinophils. This anti-CD30 mAb-induced eosinophil apoptosis is inhibited by the addition of inhibitors of p38, ERK1/2 mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. However, there is little data investigating the role of Bcl-2 and caspases in eosinophil apoptosis induced by anti-CD30 mAb. We sought to determine whether anti-CD30 mAb induces human eosinophil apoptosis via Bcl-2 and caspase pathways., Methods: Peripheral blood was drawn from 37 healthy volunteers. The CD30 expression on eosinophils was measured at various time points. Eosinophils were then cultured in plates precoated with anti-CD30 mAb (clone Ber-H8), isotype control immunoglobulin G 1 , interleukin (IL)-5, or dexamethasone. Western blot analysis was performed to determine the expression of Bcl-2, procaspase-8, -9, and -3, and caspase-8, -9, and -3 after cross-linking of CD30. Human eosinophils were also cultured in plates precoated with anti-CD30 mAb (clone Ber-H8) in the presence or absence of caspase-9 or -3 inhibitors. Eosinophil apoptosis was assessed using flow cytometry., Results: The addition of anti-CD30 mAb significantly increased eosinophil apoptosis compared with controls. In western blot analysis, the addition of anti-CD30 mAb significantly decreased the expression of Bcl-2 and procaspase-9 and -3 and increased the expression of caspase-9 and -3. The addition of caspase-9 or -3 inhibitors decreased anti-CD30 mAb-induced human eosinophil apoptosis. Procaspase-8 or caspase-8 expression was not changed in response to various stimuli., Conclusion: Anti-CD30 mAb-induced human eosinophil apoptosis is likely to be mediated through Bcl-2 and caspase-9 and -3., (Copyright © 2015. Published by Elsevier B.V.)

Atrial fibrillation (AF) is common in dialysis patients. However, clinical characteristics and outcomes of dialysis patients with AF are poorly understood. The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. Follow-up data were available for 3713 patients with a median follow-up of 2.8 years. We compared clinical characteristics and outcomes between the dialysis group (n = 92; 2.5 %) and others. The dialysis group had more various co-morbidities, with a mean CHADS 2 score of 2.5, and the rate of warfarin prescription was 38 %. The annual incidence rates of stroke or systemic embolism (SE), major bleeding, and all-cause death in the dialysis group were 4.0, 5.1, and 20.9 per 100 person-years, respectively. There was no significant difference in the incidence rate of stroke/SE between the dialysis group and the non-dialysis group [hazard ratio (HR) 1.74 (95 % confidence interval (CI) 0.74-3.42)]. The incidence rates of major bleeding, all-cause death, and the composite of stroke/SE and all-cause death in the dialysis group were higher than those in the non-dialysis group [major bleeding: HR 3.09 (95 % CI 1.46-5.72), all-cause death: HR 3.51 (95 % CI 2.48-4.81), the composite of stroke/SE and all-cause death: HR 2.99 (95 % CI 2.15-4.05)]. Among dialysis patients, warfarin did not affect major clinical events including stroke/SE, bleeding or all-cause death. Among AF patients, those receiving dialysis showed higher incidence of major bleeding and all-cause death compared with non-dialysis patients, but the risk of stroke/SE was not particularly high., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm .

Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameter > 45 mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (n = 1,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40-2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18-3.25; p < 0.01; with OAC; HR: 1.83, 95% CI: 1.21-2.82; p < 0.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25-2.42; p < 0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients.

Activation of opioid and cannabinoid receptors expressed in nociceptors induces effective antihyperalgesia. In this study, we examined whether combinations of opioid and cannabinoid receptor agonists directed at the injured site would enhance therapeutic effectiveness. Behavioral pharmacology experiments were performed to compare the effects of DAMGO, a selective agonist for μ-opioid receptor (MOR), ACPA, a specific agonist for CB1, and combinations of DAMGO and ACPA in attenuating complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in the rat hindpaw. DAMGO (1μg-1mg) or ACPA (1μg-2mg) was administered into the inflamed paw when mechanical hyperalgesia was fully developed. When administered individually, DAMGO and ACPA dose-dependently reversed the mechanical hyperalgesia. DAMGO displayed a lower ED50 value (57.4±2.49μg) than ACPA (111.6±2.18μg), but ACPA produced longer lasting antihyperalgesic effects. Combinations of DAMGO and ACPA also dose-dependently attenuated mechanical hyperalgesia, but the antihyperalgesic effects were partial and transient even at high doses. Using isobolographic analysis, we determined that combined treatment with DAMGO and ACPA produced antagonistic effects with the observed ED50 of 128.4±2.28μg. Our findings showed that MOR and CB1 agonists directed at the inflamed site effectively attenuate mechanical hyperalgesia when administered individually, but exert opposing effects when administered together. The antagonistic interactions between the two classes of drugs at the inflamed site suggest distinct mechanisms unique to peripheral nociceptors or inflamed tissue, and therefore require further studies to investigate whether the therapeutic utility of the combined drug treatments in chronic pain conditions can be optimized., (Copyright © 2016 Elsevier Inc. All rights reserved.)

High sodium intake is a well-known risk factor for elevated blood pressure and is responsible for a higher incidence of cardiovascular events. Reports have suggested an association of sodium intake with insulin resistance (IR) and type 2 diabetes mellitus in adults. However, evidence on an association between sodium intake assessed on the basis of urinary sodium excretion and IR in adolescents is scarce. The present study aimed at investigating the association between urinary sodium excretion and IR among South Korean adolescents.This population-based, cross-sectional study analyzed the data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) 2009 to 2010. The data of a total of 1353 adolescents (779 boys and 574 girls) were included in the final analysis. Spot urine samples were collected, and urinary sodium excretion was estimated by using the urinary sodium concentration (U[Na]), U[Na] to urinary creatinine ratio (U[Na]/Cr), and U[Na] to specific gravity unit (SGU) ratio (U[Na]/SGU). IR was assessed by using the homeostasis model assessment of IR (HOMA-IR). Hierarchical multivariable logistic regression analysis was performed to assess the risk for a high HOMA-IR according to urinary sodium excretion.The mean levels of U[Na], U[Na]/Cr, and U[Na]/SGU were significantly higher in subjects in the highest HOMA-IR quartile (Q4) than in subjects in the lowest, second, or third quartiles (Q1-3) of HOMA-IR. The mean values of HOMA-IR and several cardiometabolic parameters tended to progressively increase with the U[Na], U[Na]/Cr, and U[Na]/SGU quartiles. Q3 of U[Na] was at a significantly higher risk than Q1 of U[Na] of an association with Q4 of HOMA-IR, after adjustment for confounding variables. Q3 and Q4 of U[Na]/Cr and U[Na]/SGU, respectively, had significantly higher risks, than the respective Q1s, of an association with Q4 of HOMA-IR. The risk of an association with Q4 of HOMA-IR demonstrated significantly increasing trends with increasing quartiles of U[Na], U[Na]/Cr, and U[Na]/SGU irrespective of confounding factors.Urinary sodium excretion was positively associated with IR in South Korean adolescents. The monitoring and control of urinary sodium excretion may be recommended as an important intervention for the prevention of IR and related diseases in adolescents., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Atrial fibrillation (AF) is increasingly prevalent with age, and increasing age is an independent risk factor for ischemic stroke. Oral anticoagulant (OAC) therapy use in the extreme elderly (aged ≥ 85 years) is challenging., Methods: The Fushimi AF Registry is a community-based prospective study of Japanese patients with AF (79 participating medical institutions in Fushimi-ku, Kyoto, Japan). Patient enrollment started in March 2011, and follow-up data were available for 3,304 patients as of July 2014. We compared clinical characteristics and outcomes between the extreme elderly group (n = 479 [14.5%]) and other age-groups., Results: The extreme elderly group had a higher prevalence of major comorbidities and risk scores for stroke but received fewer OACs. After a mean follow-up of 2.0 years, end points in the extreme elderly group were as follows: all-cause death, 17.6; stroke/systemic embolism, 5.1; and major bleeding, 2.0 per 100 person-years. Extreme age was associated with a higher incidence of combined stroke/systemic embolism and all-cause death (hazard ratio [HR], 3.20; 95% CI, 2.66-3.84; P < .01) and higher incidences of stroke/systemic embolism (HR, 2.57; 95% CI, 1.77-3.65; P < .01) and mortality (HR, 3.48; 95% CI, 2.84-4.25; P < .01) compared with other patients (aged ≤ 84 years). The incidence of major bleeding was not significantly different (HR, 1.40; 95% CI, 0.78-2.36; P = .25)., Conclusions: In the present community-based prospective cohort, Japanese extreme elderly patients with AF had a higher incidence of stroke but similar major bleeding risks compared with the younger AF population., Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000005834; URL: http://www.umin.ac.jp/ctr/index.htm., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pentraxin 3 (PTX-3) is an acute-phase protein that increases in the plasma during inflammation., Objective: We aimed to evaluate the usefulness of PTX-3 as a clinical marker in children with lower respiratory tract infection (LRTI) and examine the correlation of PTX-3 with other biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT)., Methods: We enrolled 117 consecutive patients admitted to Seoul St. Mary's Hospital with LRTI using the WHO criteria. We recorded data on fever duration and peak temperature before admission, duration of fever after admission, respiratory rate, heart rate, oxygen saturation upon admission, duration of oxygen supplementation, and duration of hospital stay. Upon admission, white blood cell (WBC) count, erythrocyte sedimentation rate, CRP level were measured. Multiplex respiratory virus polymerase chain reaction was performed using nasal swabs. PTX-3, PCT, and various cytokines were measured after the study had been completed., Results: We found that there was no significant difference in the level of PTX-3 according to the type of viral infection. PTX-3 levels showed a significant correlation with PCT levels, but not with levels of CRP. The level of PTX-3 showed a significant correlation with peak temperature and duration of fever before admission as well as interleukin (IL)-6 levels. PCT levels showed a significant correlation with IL-6 and granulocyte-colony stimulating factor levels, peak temperature, and duration of fever before admission, and duration of hospital stay. CRP levels showed a significant correlation with duration of fever before admission, total WBC count, and neutrophil count. PCT levels significantly predicted a hospital stay of 7 days or more. PTX-3, PCT, and CRP levels showed no correlation with any other clinical features., Conclusion: PTX-3 reflected disease severity but failed to predict length of hospital stay. Further studies evaluating the use of PTX-3 as a biomarker in mild LRTI would be useful., (© 2015 Wiley Periodicals, Inc.)

In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm(-2) . After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background and Purpose: There is controversy on the relationship of the type of atrial fibrillation (AF) to stroke. Although several studies show that patients with paroxysmal AF (PAF) have a stroke risk similar to those with persistent or permanent AF, recent studies suggest that PAF is associated with a lower rate of stroke. Limited data on stroke risk associated with PAF are evident in Asian populations., Methods: The Registry Study of Atrial Fibrillation Patients in Fushimi-ku (Fushimi AF Registry) is a community-based survey of patients with AF in Fushimi-ku, Kyoto, Japan. Patients were categorized into 2 types of AF: PAF or sustained (persistent or permanent) AF. We compared clinical events between PAF (n=1588) and sustained AF (n=1716)., Results: Patients with PAF were younger, had less comorbidities, and received oral anticoagulants (OAC) less commonly. A lower risk of stroke/systemic embolism during follow-up period in the patients with PAF was consistently observed (non-OAC users: hazard ratio, 0.45; 95% confidence intervals, 0.27-0.75; P<0.01 and OAC users: hazard ratio, 0.59; 95% confidence interval, 0.35-0.93; P=0.03). The composite end point of stroke/systemic embolism/all-cause mortality was also lower in PAF, whether among OAC users (hazard ratio, 0.77; 95% confidence interval, 0.59-0.99; P=0.046) or non-OAC users (hazard ratio, 0.59; 95% confidence interval, 0.46-0.75; P<0.01). On multivariate analysis, PAF was an independent predictor of lower stroke/systemic embolism risk., Conclusions: In this large cohort of Japanese patients with AF, PAF was independently associated with lower incidence of stroke/systemic embolism than sustained AF. This may aid decision making for anticoagulation, especially in those patients with AF with few stroke risk factors., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834., (© 2015 American Heart Association, Inc.)

Background: Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in 'real-world' AF patients are limited, especially from large prospective Asian cohorts., Methods: The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for 'death, stroke, and systemic embolism (SE)' during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline., Results: The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24-2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25-2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25-2.30), heart failure (HR: 1.59, 95% CI: 1.17-2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16-2.02), and anemia (HR: 2.41, 95% CI: 1.78-3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry., Conclusions: Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients.

Bronchiolitis obliterans syndrome (BOS) is a chronic graft-versus-host disease that occurs in the lungs after hematopoietic stem cell transplantation (HSCT). Serial screening pulmonary function test (PFT) is recommended after transplantation for early diagnosis of BOS. However, little is known about the value or the optimum methods of serial PFT in this context. One hundred and 10 consecutive patients of 6 to 17 years of age at the time of transplantation who underwent allogeneic HSCT were recruited for this study. Screening PFTs were performed 1 week before transplantation and 3, 6, 9, and 12 months after transplantation. When findings of obstructive lung disease were found on PFT, chest high-resolution computed tomography was performed. Of the 110 patients, 5 (4.5%) developed BOS. Of the 5 patients who developed BOS, 2 patients were diagnosed early by screening PFT. However, screening PFT did not allow for early diagnosis of BOS in the other 3 patients because BOS developed after 12 months of transplantation, which is beyond the PFT screening period. In conclusion, trimonthly PFTs performed through 12 months after transplantation in patients who underwent allogeneic HSCT helped in the early diagnosis of BOS; however, there are some limitations to this screening protocol. Future studies will aid in the development of a new screening protocol that can subsequently be evaluated.

Gingival recession represents a clinical condition in adults frequently encountered in the general dental practice. Clinicians often face dilemmas of whether or not to treat such a condition surgically. An initial condensed literature search was performed using a combination of gingival recession and surgery controlled terms and keywords. An analysis of the search results highlights the limited understanding of the factors that guide the treatment of gingival recession. Understanding the cause, prognosis, and treatment of gingival recession continues to offer many unanswered questions and challenges in periodontics as we strive to provide the best care possible for our patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The microflora hypothesis may be the underlying explanation for the growth of inflammatory disease. In addition to many known affecting factors, knowing the gut microbiota of healthy newborns can help to understand the gut immunity and modulate it., Objectives: This study examined the microbiota of healthy newborns from urban regions., Patients and Methods: We enrolled 128 full-term newborns, born at Seoul St. Mary and St. Paul hospital from January 2009 to February 2010. All 143 samples of feces were cultivated in six culture plates to determine the amounts of total bacteria, anaerobes, gram-positive bacteria, coliforms, lactobacilli, and bifidobacteria. The samples were evaluated with a bivariate correlation between coliforms and lactobacilli. Terminal restriction fragment length polymorphism (T-RFLP) analysis with HhaI and MspI and a clustering analysis were performed for determination of diversity., Results: Bacteria were cultured in 61.5% of feces in the following order: anaerobes, gram-positive bacteria, lactobacilli, coliform, and bifidobacteria. The growth of total bacteria and lactobacilli increased in feces defecated after 24 hours of birth (P < 0.001, P = 0.008) and anaerobes decreased (P = 0.003). A negative correlation between the growth of lactobacilli and coliforms was found (r = -463, P < 0.001)., Conclusions: This study confirms that bacterial colonization of healthy newborns born in cities is non-sterile, but has early diversification and inter-individuality.