Risk factors for in-hospital acquisition of carbapenem-resistant Enterobacterales in patients with severe burns.

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. FINDINGS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P = 0.018), abbreviated burn severity index score ≥9 (P = 0.012), and mechanical ventilation (P < 0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P = 0.048). CONCLUSION: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

First Report of the Korean Lung Transplantation Registry.

BACKGROUND: The Korean Organ Transplantation Registry (KOTRY) began to register lung transplants in 2015. This is an initial report on the status of patients receiving lung transplants over the past 2 years. METHODS: We analyzed a total of 69 patients who received lung transplants in 2015 and 2016 and who registered with the KOTRY. RESULTS: The 69 patients were treated in 5 institutions. The average (SD) donor age was 39.2 (12.6) years; there were 40 male patients. The average (SD) recipient age was 55.7 (10.0) years, and the number of male recipients was 46. A total of 66 patients underwent bilateral lung transplantation, 3 underwent single-lung transplantation, and 1 underwent simultaneous heart-lung transplantation. The most frequent indication for lung transplantation was idiopathic pulmonary fibrosis (35 patients), followed by connective tissue disease-related interstitial lung disease (9) and acute respiratory failure (8). Prior to transplantation, 23 patients required ventilator care, and 12 required extracorporeal membrane oxygenation while on the waiting list. Episodes of acute rejection during follow-up were reported in 4, 2, 1, and 1 patients at 3, 6, 9, and 12 months, respectively. Infections requiring hospitalization were reported in 27, 10, 4, and 3 patients at 3, 6, 9, and 12 months, respectively. CONCLUSION: The establishment of KOTRY renders it possible to collect nationwide data on lung transplantation, improving research on the topic and clarifying clinical feasibility.

Erythrocyte sedimentation rate measured using microhemagglutination is not elevated in monoclonal gammopathy compared with other diseases.

BACKGROUND: The erythrocyte sedimentation rate (ESR) as measured using the Westergren method is extremely elevated in patients with monoclonal gammopathy (MG) owing to the abundance of positively charged paraproteins. However, it has not been determined if the ESR is likewise high in patients with MG when measured using alternate ESR methods. METHODS: The ESR was measured using both the modified Westergren and microhemagglutination method (TEST1) in 36 patients with MG and in 159 individuals with other diseases. RESULTS: Erythrocyte sedimentation rates measured by the Westergren vs microhemagglutination methods showed substantial, but not remarkably high correlation. ESR measured using the Westergren method was higher in MG than in non-MG patients; however, ESR measured using microhemagglutination was not different in the 2 groups, resulting in a larger ΔESR (microhemagglutination ESR-Westergren ESR) in MG patients. When considered as continuous variables, none of the tested interfering plasma proteins (C-reactive protein, globulin, or fibrinogen) showed substantial correlations with Westergren or microhemagglutination ESRs. MG and low hematocrit were the only factors independently associated with ΔESR on multivariate analysis. CONCLUSION: We demonstrated, for the first time, that the ESR as measured by microhemagglutination is not elevated in patients with MG compared with those without. The ESR does not correlate with a particular plasma protein, showing that its measurement is multifactorial. The presence of MG is an independent factor for ΔESR.

A novel indeno[1,2-b]pyridinone derivative, a DNA intercalative human topoisomerase IIα catalytic inhibitor, for caspase 3-independent anticancer activity.

A novel 2-(furan-2-yl)-4-(pyridin-2-yl)-5H-indeno[1,2-b]pyridin-5-one (TI-1-190) was synthesized using a simple microwave-assisted method and its mode of action was systematically characterized. It is a DNA intercalative human topoisomerase IIα catalytic inhibitor with much stronger activity and less DNA toxicity than etoposide, a topoisomerase II poison. TI-1-190 displays caspase 3-independent anticancer activity, unlike etoposide.

Once-daily dosing of amikacin for treatment of Mycobacterium abscessus lung disease.

SETTING: Tertiary referral centre, Samsung Medical Center, South Korea. OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. DESIGN: A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 µg/ml was achieved in 31.3% (15/48) of patients in the first week, 68.8% (33/48) in week 2, 91.7% (44/48) in week 3 and 95.8% (46/48) in week 4. Transient nephrotoxicity developed in 6.3% (3/48) of patients and ototoxicity in 25.0% (6/24), which was determined by audiogram as hearing loss, asymptomatic in five patients and tinnitus in one. Multivariate analysis revealed that the highest drug concentration 12 h after administration was significantly associated with the development of toxicities (adjusted odds ratio 1.862, P = 0.047). CONCLUSION: Our results suggest that once-daily AMK for 4 weeks with a target Cmax of 55-65 µg/ml can be used in patients with M. abscessus lung disease, with careful monitoring of toxicity.

A comparative study of efficiency droop and internal electric field for InGaN blue lighting-emitting diodes on silicon and sapphire substrates.

We investigated the efficiency droop and polarization-induced internal electric field of InGaN blue light-emitting diodes (LEDs) grown on silicon(111) and c-plane sapphire substrates. The efficiency droop of the LED sample grown on silicon substrates was considerably lower than that of the identically fabricated LED sample grown on sapphire substrates. Consequently, the LED on silicon showed higher efficiency at a sufficiently high injection current despite the lower peak efficiency caused by the poorer crystal quality. The reduced efficiency droop for the LED on silicon was attributed to its lower internal electric field, which was confirmed by reverse-bias electro-reflectance measurements and numerical simulations. The internal electric field of the multiple quantum wells (MQWs) on silicon was found to be reduced by more than 40% compared to that of the MQWs on sapphire, which resulted in a more homogenous carrier distribution in InGaN MQWs, lower Auger recombination rates, and consequently reduced efficiency droop for the LEDs grown on the silicon substrates. Owing to its greatly reduced efficiency droop, the InGaN blue LED on silicon substrates is expected to be a good cost effective solution for future lighting technology.

Liquid culture enhances diagnosis of patients with milder forms of non-tuberculous mycobacterial lung disease.

OBJECTIVE: To evaluate the proportion and clinical characteristics of patients with non-tuberculous mycobacteria (NTM) lung disease diagnosed based on positive culture results in liquid medium only. METHODS: We reviewed the medical records of 978 patients diagnosed with NTM lung disease. All clinical samples were cultured in both solid and liquid media. RESULTS: Of the 978 patients, 111 (11.3%) were culture-positive in liquid medium only (liquid culture group), and 867 (88.7%) (solid culture group) on solid medium, regardless of the culture results in liquid medium. At the time of diagnosis, the liquid culture group was less likely than the solid culture group to have haemoptysis (11.7% vs. 20.0%, P = 0.04), positive sputum smear for acid-fast bacilli (14.4% vs. 50.2%, P < 0.001) or the fibrocavitary form of NTM lung disease (3.6% vs. 14.6%, P = 0.001). During the median follow-up period of 28.9 months (interquartile range 19.1-41.6), the proportion of patients requiring antibiotic treatment was lower in the liquid culture group than in the solid culture group (44.1% vs. 61.6%, P < 0.001). CONCLUSIONS: Liquid media culture is helpful in the diagnosis of patients with less severe forms of NTM lung disease.

Characteristics of extracellular cyclic AMP-dependent protein kinase as a biomarker of cancer in dogs.

OBJECTIVE: Early and proper diagnosis of cancer is the most critical factor for the survival and treatment of veterinary cancer patients. In this study, we evaluated extracellular cyclic AMP-dependent protein kinase A (ECPKA) level in serum as a useful cancer biomarker in dogs. METHODS: ECPKA levels were detected in sera from dogs with cancers (n = 48), benign tumours (n = 18), and non-tumour diseases (n = 102) as well as healthy control dogs (n = 54) utilizing enzyme-linked immunosorbent assay (ELISA). RESULTS: Sera from dogs bearing various types of cancer exhibited markedly increased levels of ECPKA by up to 7.1-, 8.8-, and 10.9-fold compared with those from dogs harbouring benign tumours, dogs with non-tumour diseases, and healthy control dogs, respectively (P < .0001). In addition, serum ECPKA level did not show statistically significant correlation with gender, breed, or age of dogs or their non-cancerous disease conditions. CONCLUSION: Our data strongly propose that detection of serum ECPKA level is a potential and specific diagnostic tool for cancer in dogs.

The 100 most-cited articles on non-tuberculous mycobacterial infection from 1995 to 2015.

SETTING: Citation analyses aid in assessing quality, trends and future directions of research fields. OBJECTIVE: To identify the most influential articles on infections caused by non-tuberculous mycobacteria (NTM) in the last 20 years. DESIGN: We performed a cited reference search of the Web of Science database from 1995 to 2015. The 100 most cited articles on NTM infections were analysed. RESULTS: The top 100 articles were cited 114-1471 times, and were published from 1995 to 2013. Sixty-five were laboratory-based, basic science articles, with the major topics being pathophysiology (n = 20) and molecular methods for NTM identification (n = 15). Among the 35 non-laboratory studies, major topics were clinical management (n = 15) and epidemiology (n = 14). The top article was a clinical treatise on the management of NTM disease, published in 2007. Although there was a correlation between article rank and journal impact factor (P = 0.043, ρ = -0.202), the five articles from the journals with highest impact factors did not rank among the top 10 articles. CONCLUSION: A large proportion of influential articles on NTM infection are basic scientific studies, and the most influential articles are not always published in high-impact journals.

Clinical Relationship between Cholestatic Disease and Pituitary-Dependent Hyperadrenocorticism in Dogs: A Retrospective Case Series.

BACKGROUND: A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). HYPOTHESIS/OBJECTIVES: Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. ANIMALS: Sixty-five client-owned dogs with naturally occurring PDH. METHODS: This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. RESULTS: The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane.

Elevated leukocyte count is associated with periodontitis in Korean adults: the 2012-2014 KNHANES.

OBJECTIVE: Both an elevated leukocyte count and periodontitis share well-recognized associations with cardiometabolic diseases. This cross-sectional study aimed to identify whether the leukocyte count is associated with periodontitis in a nationally representative Korean adult population. MATERIALS AND METHODS: Data from 9391 participants (3659 males and 5732 females) enrolled in 2012-2014 Korean National Health and Nutrition Examination Survey were analyzed. Leukocyte quartiles were categorized as follows: 3000 ≤ Q1 ≤ 4870, 4880 ≤ Q2 ≤5790, 5800 ≤ Q3 ≤ 6840, and 6850 ≤ Q4 ≤ 10000 cells/µl. Periodontitis was defined as scoring greater than or equal to 'code 3' in at least one site according to the WHO's Community Periodontal Index. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for periodontitis in each leukocyte count quartile were calculated using multiple logistic regression analyses. RESULTS: The prevalence of periodontitis was directly correlated with increasing leukocyte quartiles: 19%, 20.4%, 24.3%, and 30.3%. Compared with the lowest leukocyte quartile group, the OR (95% CI) for periodontitis of the highest leukocyte quartile was 1.558 (1.285-1.891) after controlling for confounding factors. CONCLUSION: An elevated leukocyte count was positively associated with the presence of periodontitis.

Implication of vitamin D-associated factors in patients with non-tuberculous mycobacterial lung disease.

BACKGROUND: Little information is available regarding vitamin D-associated factors in patients with non-tuberculous mycobacteria (NTM) lung disease. OBJECTIVE: To determine the association between vitamin D-related factors and susceptibility to NTM lung disease. DESIGN: The relative gene expression levels of cathelicidin (CAMP), defensin (DEFB4), vitamin D receptor (VDR) and 1-hydroxylase (CYP27B1), as well as the serum levels of 25-hydroxyvitamin D (25[OH]D), cathelicidin (LL-37), defensin (hBD-2) and vitamin D-binding protein (DBP) from 82 patients with NTM lung disease and 28 control subjects were analysed. RESULTS: Gene expression of CAMP and DEFB4 was significantly higher, and gene expression of VDR and CYP27B1 was significantly lower, in NTM patients than controls. Serum LL-37 and hBD-2 levels were not significantly different between NTM patients and controls; however, the serum DBP level was higher in NTM patients than controls. The serum vitamin D status of patients did not correlate with serum LL-37, hBD-2, or DBP concentration or gene expression of CAMP, DEFB4, VDR or CYP27B1. CONCLUSION: A higher level of gene expression for antimicrobial peptide is more likely to be associated with NTM lung disease than serum vitamin D status.

A Study of Piezoelectric Field Related Strain Difference in GaN-Based Blue Light-Emitting Diodes Grown on Silicon(111) and Sapphire Substrates.

We investigate the strain difference in InGaN/GaN multiple quantum wells of blue light-emitting diode (LED) structures grown on silicon(1 11) and c-plane sapphire substrates by comparing the strength of piezo-electric fields in MQWs. The piezo-electric fields for two LED samples grown on silicon and sapphire substrates are measured by using the reverse-bias electro-reflectance (ER) spectroscopy. The flat-band voltage is obtained by measuring the applied reverse bias voltage that induces a phase inversion in the ER spectra, which is used to calculate the strength of piezo-electric fields. The piezo-electric field is determined to be 1.36 MV/cm for the LED on silicon substrate and 1.83 MV/cm for the LED on sapphire substrate. The ER measurement results indicate that the strain-induced piezo-electric field is greatly reduced in the LED grown on silicon substrates consistent with previous strain measurement results by micro-Raman spectroscopy and high-resolution transmission electron microscopy.

Comparison of Strain in GaN-Based Blue Light-Emitting Diode Grown on Silicon(111) and Sapphire Substrates.

We compare the strain states and device performances of GaN-based blue light-emitting diodes (LEDs) grown on Si(111) and sapphire substrates. The strain characteristics are investigated using micro-Raman spectroscopy and high-resolution transmission electron microscopy. These analyses reveal that GaN layer grown on Si has a residual tensile strain in contrast to a compressive strain for GaN on sapphire, and quantum wells (QWs) on GaN/Si experience reduced lattice mismatch than those of GaN/sapphire. When external quantum efficiencies of LED on sapphire and Si substrates are compared, the LED on Si shows better efficiency droop characteristics and this is attributed to a decrease in piezo-electric field strength in InGaN/GaN layers owing to reduced lattice mismatch.

Changes in serum immunomolecules during antibiotic therapy for Mycobacterium avium complex lung disease.

Little information is available regarding changes in immune status for patients with Mycobacterium avium complex (MAC) lung disease during antibiotic therapy. Serum immunomolecules from 42 patients with MAC lung disease were assayed comparatively using an array-based system according to (i) patients with MAC lung disease at the time of diagnosis versus healthy controls and (ii) alterations after 12 months of antibiotic therapy in the MAC lung disease group. In addition, cytokine analyses were performed to determine whether cytokine responses were associated specifically with the disease phenotype, treatment outcome and aetiological agent. Notably, the serum concentrations of type 1 cytokine-associated molecules, such as CD40L, interferon (IFN)-γ, interleukin (IL)-8 and IL-23, were decreased significantly in patients at the time of diagnosis, suggesting that these molecules may serve as indicators of host susceptibility to MAC disease. Although the overall serum level of T helper type 1 (Th1)-related molecules, such as CD40L and IFN-γ, was restored after treatment, Th17-related cytokines, such as IL-17 and IL-23, were down-regulated significantly at 12 months post-treatment compared to pretreatment. Furthermore, these cytokine patterns differed among patient subgroups. Decreased serum concentrations of IL-17 and/or IL-23 were associated with failure of sputum conversion, the fibrocavitary disease phenotype and M. intracellulare lung disease. Thus, the reciprocal balance between Th1 and Th17 immunity during antibiotic therapy for MAC lung disease is critical for dictating the treatment response. In conclusion, a low level of Th1-related immunomolecules may perpetuate MAC lung disease, and the serum concentrations of Th17-related cytokines can reflect the treatment outcome, disease phenotype and aetiological agent.

Genotyping of Mycobacterium intracellulare isolates and clinical characteristics of lung disease.

BACKGROUND: Variable number of tandem repeats (VNTR) loci were recently identified in Japanese isolates of Mycobacterium intracellulare. We hypothesised that some mycobacterial genotypes are more virulent than others, resulting in particular genotypes being associated with disease phenotype and progression. OBJECTIVE: To evaluate the VNTR loci of M. intracellulare in clinical isolates from Korean patients, and investigate the association between mycobacterial genotype and disease phenotype and progression. DESIGN: In total, 70 M. intracellulare clinical isolates were genotyped using 16 M. intracellulare VNTR loci. RESULTS: VNTR typing showed strong discriminatory power and genetic diversity for molecular epidemiological studies of M. intracellulare. In a phylogenetic tree, the M. intracellulare clinical isolates were divided into two clusters (A and B). Cluster A was observed more frequently (77%) than Cluster B; however, there was no association between the clinical characteristics, disease progression, drug susceptibility and clusters based on VNTR genotyping. CONCLUSIONS: VNTR typing could be used for epidemiological studies of M. intracellulare lung disease; however, no association was found between the specific VNTR genotypes of M. intracellulare and the clinical characteristics of Korean patients.

Toxocariasis as a cause of new pulmonary infiltrates.

SETTING: Patients with new pulmonary infiltrates on chest computed tomography (CT) scans at a tertiary centre in South Korea. OBJECTIVE: To demonstrate associations among radiological changes, blood eosinophilia (E) and Toxocara (T) seropositivity. DESIGN: We retrospectively reviewed blood eosinophilia, Toxocara seropositivity, history of raw meat intake and radiological features, and divided study patients into four groups according to blood eosinophilia and Toxocara seropositivity. RESULTS: Among 150 patients, 62 were E- and T-positive (E+T+), 45 were E-negative and T-positive (E-T+), 7 were E-positive and T-negative (E+T-), and 36 were E- and T-negative (E-T-). History of raw meat intake was found in 95 (63%) patients. The type and number of lesions on CT did not show any significant differences among the four groups. Among 119 patients who were not diagnosed with a specific disease, transient or migrating lesions were seen in 93% of E+T+, 93% of E-T+, 80% of E+T- and 52% of E-T- patients (P < 0.0001). Furthermore, the frequencies of migrating or new lesions and improvement were significantly higher in the Toxocara-positive group (88/95, 93%) than in the Toxocara-negative group (14/24, 58%; P = 0.002). CONCLUSION: Transient and migratory pulmonary infiltrates on chest CT scans were associated with blood eosinophilia and Toxocara seropositivity. Clinicians should consider asymptomatic toxocariasis as a cause of unexplained new pulmonary infiltrates in countries with dietary habits of raw meat intake.

Clinical significance of mycobacterial genotyping in Mycobacterium avium lung disease in Korea.

SETTING: A recent study in Japan found that mycobacterial genotyping was associated with disease progression and susceptibility to certain drugs in Mycobacterium avium lung disease. However, it is not known whether this association is true in other populations. OBJECTIVE: To investigate the association between mycobacterial genotype, clinical characteristics and the progression of M. avium lung disease in Korean patients. DESIGN: A total of 102 M. avium clinical isolates were genotyped using M. avium tandem repeats-variable number of tandem repeats (MATR-VNTR). RESULTS: MATR-VNTR typing demonstrated a high discriminatory power and genetic diversity for molecular epidemiological studies of M. avium. In the phylogenetic tree, the M. avium clinical isolates were divided into three major clusters: A, B and C. Cluster A was observed most frequently (64/102, 63%), whereas cluster C was found in a minor proportion of the isolates (8/102, 8%). However, there was no association between the clinical characteristics, disease progression and drug susceptibility and the phylogenetic tree based on VNTR genotyping. CONCLUSIONS: MATR-VNTR genotyping may be useful for epidemiological studies of M. avium lung disease; however, no association was found between the specific VNTR genotypes of M. avium and the clinical characteristics of Korean patients.

A study on knowledge and attitude toward brain death and organ retrieval among health care professionals in Korea.

PURPOSE: The practice of retrieving vital organs from brain-dead donors is legally and medically accepted in Korea, but health care professionals' beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the knowledge and attitudes of health care professionals to the concepts of brain death and organ retrieval. METHODS: Data were collected using a 41-item questionnaire during a week in June 2011. Sixty-one doctors and 109 nurses from five hospitals with more than 2000 beds in Seoul, Korea, participated in the survey. The data was analyzed using SPSS version 17.0 (SPSS Inc. Chicago, Illinois, USA). RESULTS: There were statistically significant differences in the scores on knowledge according to marital status (P = .001) education level (P = .019), whether the participants were informed about organ donation from a brain-dead donor (P = .002), and the participant's experience managing potential brain-dead patients (P = .037). There were statistically significant differences in the scores on the attitude according to gender (P < .001), age (P < .001), marital status (P < .001), education level (P = .003), job position (P < .001), and the participant's experience referring brain-dead patients to the hospital-based organ procurement organization (P = .001). Significantly, attitude's positively correlated with knowledge about brain-dead organ donation (P < .001). CONCLUSION: Compared with previous studies, the knowledge and attitudes of health care professionals' regarding brain death and organ retrieval were not improved. There are passive attitudes to brain death and organ retrieval. More research must be performed to promote knowledge and understanding toward brain death and organ retrieval among health care professionals.