Interstitial lung disease and risk of mortality: 11-year nationwide population-based study.

BACKGROUND: Patients with interstitial lung disease (ILD) constitute a substantial disease burden. Although ILD outcomes have been investigated, the risk of death due to ILD has not been studied in the light of confounders and comorbidities. In this nationwide, 11-year longitudinal, population-based study, we aimed to discover if ILD is an independent risk factor for mortality. DESIGN: Data on 1 031 392 (2.2%) randomly selected subjects from 47 279 373 Korean residents were collected from the 2002 Korean National Health Insurance database. The ILD group comprised patients with an initial diagnosis of ILD between January 2003 and December 2007. Each patient was followed until 2013. We used Cox proportional hazard regression analyses to calculate the risk of death adjusted for comorbidities and confounders. RESULTS: ILD developed in 783 of the 303 385 subjects during the 5-year period (51 per 100 000 person-years). Death occurred in 157 (23.2%) cases and 272 controls (10.4%). ILD was significantly associated with the risk of death (hazard ratio 2.1, 95% confidence interval [CI] 1.6-2.7) and for those aged 40-59, 60-69 and 70 years. A high proportion of patients with ILD died due to respiratory causes. CONCLUSION: ILD patients had a significantly higher risk of death than matched controls, after adjustment for potential confounders and comorbidities.

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding.

This corrects the article DOI: 10.1038/onc.2011.331.

Incidence of idiopathic pulmonary fibrosis in Korea based on the 2011 ATS/ERS/JRS/ALAT statement.

OBJECTIVE: To estimate the annual incidence rate of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) in Korea. DESIGN: A retrospective cohort design using the Korean Health Insurance Review and Assessment Service (HIRA) database spanned the period from January 2008 to December 2012. Patients with ILD and IPF were identified based on the International Classification of Disease-10 (ICD-10) diagnosis and procedure codes. Definition 1 is code J84 (ILD); Definition 2 is code J84 plus high-resolution computed tomography (HRCT), bronchoalveolar lavage (BAL) or lung biopsy; Definition 3 is code J84.1 (ILD with fibrosis); Definition 4 is code J84.1 and HRCT, BAL or lung biopsy; and Definition 5 is code J84.1A (IPF), and was specifically implemented for IPF. RESULTS: The incidence rates of ILD per 100,000 population based on Definitions 1-5 were respectively 48.5, 32.2, 16.2, 11.4 and 1.7. CONCLUSION: The incidence of ILD with fibrosis was approximately 23% of overall ILD incidence. IPF incidence was approximately 10% of the incidence of ILD with fibrosis. Based on the new ATS/ERS/JRS/ALAT statement published in 2011, the incidence rate of IPF was 1.7/100,000.

Clinical characteristics and prognosis of pneumonia and sepsis: multicenter study.

BACKGROUND: Pneumonia is the primary source of sepsis and is significantly associated with mortality. However, only a few studies focus on its clinical characteristics and outcomes. METHODS: We evaluated 500 intensive care unit patients who met severe sepsis or septic shock criteria, dividing them into two distinct groups (43%, sepsis with pneumonia; 41%, sepsis with an infection other than pneumonia). RESULTS: Moderate differences between the groups were observed. The group of sepsis with pneumonia had a higher 28-day in-hospital mortality (41% vs. 30%; P=0.02). Multivariate analysis revealed that the presence of pneumonia associated significantly with mortality (OR 1.76, 95% CI 1.11-2.78) along with cardiopulmonary resuscitation (OR 4.20, 95% CI 1.50-11.74), serum lactate ≥ 3.5 mmol/L (OR 1.92, 95% CI 1.20-3.08), and SOFA score ≥ 12 (OR 2.41, 95% CI 1.52-3.82). Survival analysis revealed for both groups that the patients with PaO2/FiO2 (PF) ratio <170 and lactate ≥ 3.5 mmol/L had a worse prognosis than the patients with PF ratio ≥ 170 and lactate ≥ 3.5 mmol/L or PF ratio <170 and lactate <3.5 mmol/L. CONCLUSION: In patients admitted with sepsis, the pneumonia infection independently predicts 28-day in-hospital mortality. Combining the levels of serum lactate and PF ratio could be a useful approach in predicting mortality of these patients.

Pleural cancer antigen-125 levels in benign and malignant pleural effusions.

OBJECTIVE: To examine the properties of mesothelial cells by measuring pleural cancer antigen 125 (CA-125) levels in different types of benign and malignant pleural effusions. DESIGN: In this retrospective study, pleural fluid was collected from 326 patients; pleural CA-125 levels were measured using radioimmunoassay. Patients were classified into five groups according to the aetiology of pleural effusions: I) tuberculosis, II) malignant, III) pyogenic, IV) congestive heart failure, and V) hepatic hydrothorax. RESULTS: CA-125 levels were significantly higher in the malignant group than in all benign groups. There was no difference in pleural CA-125 levels between transudate and exudate benign aetiologies. Although pleural CA-125 levels were significantly higher in malignant than benign effusions, about one third of malignant pleural effusions had levels of <600 U/ml. Among malignancies, there were no significant differences in pleural CA-125 levels between histological types. CONCLUSION: CA-125 levels in benign pleural effusions may not be influenced by pleural inflammation or hydrostatic or oncotic pressure changes. Pleural CA-125 levels may not be influenced by the histological type of tumour in malignant pleural effusions, suggesting that mesothelial cell properties may not be altered by these factors in the pleural space.

Paradoxical response in HIV-negative patients with pleural tuberculosis: a retrospective multicentre study.

OBJECTIVE: To evaluate the incidence, clinical characteristics and predicting factors for the development of paradoxical response in human immunodeficiency virus negative patients with isolated pleural tuberculosis (TB). DESIGN: A multicentre, retrospective cohort study including 458 patients who were diagnosed and treated with isolated pleural TB between March 2005 and February 2010. RESULTS: Paradoxical response developed in 72 patients (16%) with isolated pleural TB. The mean time to development of paradoxical response was 8.8 ± 6.4 weeks after initiation of anti-tuberculosis treatment. The main presentation of paradoxical response was aggravation of pre-existing pleural effusion in 58 patients (81%). However, the majority of the patients who developed paradoxical response had no associated symptoms (n = 49, 68%). In multiple logistic regression analysis, development of paradoxical response was independently associated with the proportion of eosinophils (adjusted OR 1.293, 95%CI 1.077-1.553) and protein concentrations (adjusted OR 0.590, 95%CI 0.397-0.878) in the pleural fluid at the time of diagnosis. CONCLUSION: Paradoxical response developed in 16% of the patients approximately 2 months after initiation of anti-tuberculosis treatment, presenting with aggravation of pre-existing pleural effusion. Development of paradoxical response was associated with the proportion of eosinophils and protein concentrations in the pleural fluid at the time of diagnosis.

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding.

The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box#3 (bp, -55 to -63) and the MIZ-1-binding elements, MRE-A (bp, -90 to -64) and MRE-B (bp, -27 to -17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp, -95 to -100) and #3 (bp, -55 to -63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.

Clinical characteristics and outcomes of H1N1-associated pneumonia among adults in South Korea.

BACKGROUND: Pneumonia has been reported to be the most life-threatening complication of influenza virus infection. OBJECTIVE: to describe clinical characteristics and determine risk factors for death among patients with H1N1-associated pneumonia. DESIGN: A retrospective cohort study included all adult patients diagnosed and treated with H1N1-associated pneumonia in 14 participating institutions between 1 May 2009 and 28 February 2010 in South Korea. Clinical outcomes were summarised and predictors for death evaluated through univariate and multivariate analysis. RESULTS: A total of 269 adult patients with H1N1-associated pneumonia were diagnosed and treated. Hospital visits or admissions peaked in November 2009, coinciding with the peak in the 2009 H1N1 epidemic in South Korea. The patients' median age was 48 years; 143 were male. Most (n = 266, 98.9%) were admitted for treatment: 97 (36.1%) required intensive care and 28 (10.4%) needed mechanical ventilation. Despite the use of antiviral and antibacterial agents, 19 patients (7.1%) died. Risk factors predictive of death included presence of malignancy (aOR 12.0, 95%CI 2.8-51.5), and pneumonia severity index (PSI) score (aOR 1.03, 95%CI 1.01-1.04). CONCLUSION: Deaths among adult patients with H1N1-associated pneumonia were not rare. Clinicians should be aware of the possibility of a poor prognosis among H1N1-associated pneumonia patients with underlying malignancy or high PSI score.

Cesium-filled single wall carbon nanotubes as conducting nanowires: scanning tunneling spectroscopy study.

Metal-filled single wall carbon nanotubes (SWCNTs) are examined for possible application to conducting wires in nanoelectronics architecture. The local electronic structure of SWCNTs partially filled with cesium atoms is studied with scanning tunneling spectroscopy. The conduction and valence bands are shifted downward with two localized states in the gap at the location where the Cs atoms are filled. From a first-principles calculation, we confirm that these two gap states are bound states originating from the two lowest conduction bands.

Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis.

BACKGROUND: Vitiligo may develop following minor physical trauma. However, in autologous epidermal grafting, depigmentation of the donor (normally pigmented) site from a suction blister is rare, even in cases displaying failure of repigmentation at the recipient (depigmented) site. OBJECTIVES: To examine whether the suction procedure is more likely to damage keratinocytes in the depigmented than in the normally pigmented epidermis of vitiligo, and to determine what kind of damage occurs to the keratinocytes. METHODS: Paired roofs of suction blisters from five patients with generalized vitiligo, five with localized and seven with segmental type, were used for the study. Multiple new lesions developed in two of the five patients with the generalized type. Apoptosis of keratinocytes in the epidermis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labelling (TUNEL) staining, with immunohistochemistry for Bax and active caspase 3. Expression of Bcl-2, Bax, FLIP and p53, activation of caspases 3, 8 and 9, and cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) in the epidermis were analysed by Western blotting in four patients with each type. RESULTS: Apoptotic keratinocytes, which stained with TUNEL and anti-Bax and antiactive caspase 3 antibodies, were scattered in the blistered epidermis, mainly in the lower portions. The depigmented epidermis displayed significantly more apoptotic keratinocytes than the normally pigmented epidermis. The numerical difference between the paired epidermides was related to the disease activity and not to the type of lesions. The number of apoptotic keratinocytes in the normally pigmented epidermis was as high as that in the depigmented epidermis in the two patients with active generalized type vitiligo. Expression of Bax and p53 in the depigmented epidermis was higher than in the normally pigmented epidermis, whereas expression of FLIP was lower. In addition, the activation of caspases 3, 8 and 9, and cleavage of PARP, were increased in the depigmented compared with the normally pigmented epidermis. The degree of difference in expression and activation was parallel to the results of the TUNEL assay. CONCLUSIONS: The keratinocytes in the depigmented compared with the normally pigmented epidermis of vitiligo may become apoptotic more easily after suction.

The Psychiatric Status Schedule for Asian Americans.

Because Asian Americans who need to be diagnosed often do not speak English, the authors translated the Psychiatric Status Schedule into several Asian languages and devised an audiovisual version of the schedule. They tested the validity of the audiovisual version by comparing the computer diagnoses derived from interviews by mental health professionals who used the standard translated version with the computer diagnoses of mental health professionals and volunteers who used the audiovisual version. Sixty subjects were diagnosed: 20 Chinese-speaking patients, 20 Korean-speaking patients, and 20 Japanese-speaking subjects. Moderate reliability was found between those who used the standard translated version and those who used the audiovisual version.