Moo Song Lee

GSTT1-null genotype is a protective factor against bladder cancer

OBJECTIVES To investigate the effects of homozygous deletions of GSTM1 and GSTT1 and smoking on bladder cancer, we conducted a case-control and ecological study. METHODS The case group consisted of 216 patients with bladder cancer and the control group of 449 healthy Koreans. Every subject was personally interviewed to obtain a detailed smoking history, and a multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes. In the ecological study, age-standardized bladder cancer incidence and frequencies of GSTM1 and GSTT1-null types, estimated prevalence of cigarette smoking, and estimated per capita consumption of cigarettes per adult according to nationality and ethnicity were included. RESULTS In the Korean case-control data, smoking history and the GSTT1-null genotype were significantly associated with bladder cancer, and the GSTM1-null genotype was not. In the univariate and multivariate analyses with the ecological data of various countries and ethnic groups, cigarette smoking positively, but the frequency of the GSTT1-null type negatively, correlated with the age-standardized bladder cancer incidence. CONCLUSIONS These results suggest that the GSTT1-negative genotype might not be a risk factor but a protective factor of bladder cancer.

Humidifier Disinfectant–associated Children’s Interstitial Lung Disease

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

A cluster of lung injury cases associated with home humidifier use: an epidemiological investigation

Background In April 2011 a tertiary hospital in Seoul, Korea reported several cases of severe respiratory distress of unknown origin in young adults. Methods To find the route of transmission, causative agent and patient risk factors of the outbreak, an investigation of the epidemic was initiated. Clinicopathological conferences led to the suspicion that the cases related to an inhalation injury. An age- and sex-matched case–control study was therefore performed to examine the inhalation exposure of the patients to various agents. Results Of the 28 confirmed cases, 18 agreed to participate. A total of 121 age- and sex-matched controls with pulmonary, allergic or obstetric disease were selected. All patients and controls completed questionnaires with questions about exposure to various inhalants. The crude ORs for patient exposure to indoor mould, humidifier use, humidifier detergent use and insecticide use were 4.4 (95% CI 1.5 to 13.1), 13.7 (95% CI 1.8 to 106.3), 47.3 (95% CI 6.1 to 369.7) and 3.9 (95% CI 1.3 to 11.7), respectively. However, when considered concurrently, indoor mould and insecticide use lost statistical significance. Moreover, humidifier use was ruled out as the cause because of a lack of biological plausibility and the weak strength of the association. This suggested that humidifier disinfectant was the cause of the outbreak. This information led the Korean government to order the removal of humidifier detergents from the market. In the years following the ban, no additional cases were detected. Conclusions Epidemiological evidence strongly suggests that the lung injury outbreak was caused by humidifier detergent use at home.

A De-identification method for bilingual clinical texts of various note types.

De-identification of personal health information is essential in order not to require written patient informed consent. Previous de-identification methods were proposed using natural language processing technology in order to remove the identifiers in clinical narrative text, although these methods only focused on narrative text written in English. In this study, we propose a regular expression-based de-identification method used to address bilingual clinical records written in Korean and English. To develop and validate regular expression rules, we obtained training and validation datasets composed of 6,039 clinical notes of 20 types and 5,000 notes of 33 types, respectively. Fifteen regular expression rules were constructed using the development dataset and those rules achieved 99.87% precision and 96.25% recall for the validation dataset. Our de-identification method successfully removed the identifiers in diverse types of bilingual clinical narrative texts. This method will thus assist physicians to more easily perform retrospective research. Graphical Abstract

Nomograms for the Prediction of Pathologic Stage of Clinically Localized Prostate Cancer in Korean Men

We analyzed the prostate cancer data of 317 Korean men with clinically localized prostate cancer who underwent radical prostatectomy at Asan Medical Center between June 1990 and November 2003 to construct nomograms predicting the pathologic stage of these tumors, and compared the outcome with preexisting nomograms. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node metastasis (LNM) using serum prostate-specific antigen (PSA), Gleason score and clinical stage. Nomograms representing percent probabilities were constructed and compared with those presented by Partin et al. by calculating areas under the receiver operating characteristics (ROC) curves. Median serum PSA at surgery was 10.8 ng/mL, and median biopsy Gleason score was 7. Overall OCD, ECE, SVI and LNM rates were 59.6%, 20.5%, 11.7% and 8.2%, respectively, and areas under the curves were 0.724, 0.626, 0.662, and 0.794, respectively. Pathologic stage of localized prostate cancer in Korean men may be predicted using the Partin table, with acceptable accuracy for OCD and LNM, but less so for ECE and SVI.

Prophylactic Effect of Erythropoietin Injection to Prevent Acute Mountain Sickness: An Open-Label Randomized Controlled Trial

This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness (AMS). This open-label, randomized, controlled trial involved 39 healthy volunteers with hemoglobin ≤15.5 g/dL who were divided randomly into erythropoietin (n=20) and control (n=19) groups. Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks. On day 1, and 7 days after the last injection (day 29), oxygen saturation (SaO2), and hemoglobin were measured. The subjects departed Seoul on day 30 and arrived at Annapurna base camp (ABC, 4,130 m) on day 34. AMS was diagnosed when headache and Lake Louise score (LLS) of ≥3 were present. Immediate descent criteria followed US Army recommendations. Two groups differ in hemoglobin levels on day 29 (15.4±1.1 vs 14.2±1.0 g/dL, P=0.001). At ABC, erythropoietin group had a significantly lower mean LLS, AMS incidence, and number of subjects who met immediate descent criteria. Multiple logistic regression analysis showed that SaO2<87% and control group, but not hemoglobin<15.0 g/dL, independently predicted satisfaction of immediate descent criteria. Erythropoietin-related adverse effects were not observed. In conclusion, erythropoietin may be an effective prophylaxis for AMS.(Clinical Trial Registry Number; NCT 01665781). Graphical Abstract

Cancer rehabilitation: experience, symptoms, and needs.

The aim of this study was to examine the experience of cancer patients undergoing rehabilitation, to identify symptoms associated with rehabilitation from cancer, and to assess the need for rehabilitation services for cancer patients. Cancer patients (n = 402) at the Asan Medical Center (Seoul, Korea) were enrolled from June to September 2008. A chart review was used to collect demographic and clinical data, including type of cancer, current treatment, time from initial diagnosis to screening, and cancer stage. Each participant provided informed consent and was then given a questionnaire that asked about experience with rehabilitation, symptoms associated with rehabilitation, and the need for different types of rehabilitation services. Clinicians recommended rehabilitation for 8.5% of patients, and 6.7% underwent rehabilitation. Among study patients, 83.8% had one or more symptoms associated with rehabilitation, and 71.6% of patients with symptoms wanted rehabilitation management. The need for rehabilitation was associated with the presence of metastasis, advanced cancer stage, time to diagnosis, and type of current treatment. Our results provide specific information about particular functional symptoms and the rehabilitative needs of subgroups of cancer patients. It is suggested to develope and implement rehabilitation programs for cancer patients.

Inhalation Lung Injury Associated with Humidifier Disinfectants in Adults

We recently established a novel disease entity presented as progressive respiratory failure associated with the inhalation of humidifier disinfectants. In April 2011, we encountered a series of peripartum patients with complaints of respiratory distress of unknown etiology, which was an uncommon phenomenon. Accordingly, we created a multidisciplinary team comprising intensivists, radiologists, pathologists, epidemiologists, and the Korea Centers for Disease Control and Prevention (KCDC). Further, we defined the disease entity and performed a case-control study, epidemiologic investigation, and animal study to determine the etiology. The study findings indicated that the lung injury outbreak was related to the inhalation of humidifier disinfectants and showed that household chemical inhalation can cause severe respiratory failure. Following the withdrawal of humidifier disinfectants from the Korean market in 2012, no such cases were reported. This tragic event is a warning that appropriate safety regulations and monitoring for potential toxic household chemicals are critical to protect public health.