Hyung-Jin Yoon

Nutritional deficit as a negative prognostic factor in patients with miliary tuberculosis

The effects of malnutrition on outcomes in miliary tuberculosis (MTB) are not well described. The aim of the present study was to find predictors for the development of acute respiratory failure (ARF) and survival in MTB patients, focusing on parameters reflecting nutritional condition. Out of the patients from three hospitals who had microbiologically or histopathologically confirmed tuberculosis, 56 patients presenting with typical disseminated pulmonary nodules on radiographs were retrospectively enrolled. A four-point nutritional risk score (NRS) was defined according to the presence of four nutritional factors: low body mass index (BMI; <18.5 kg·m−2), hypoalbuminaemia (<30.0 g·L−1), hypocholesterolaemia (<2.33 mmol·L−1) and severe lymphocytopenia (<7×105 cells·L−1). The male to female ratio was 1:3. ARF developed in 25% of patients (14 out of 56), with a 50% fatality rate. A high NRS (≥3 points) was an independent risk factor for the development of ARF and fatality. In 90-day survival analysis, ARF, severe lymphocytopenia, hypocholesterolaemia, low BMI and higher NRS were risk factors for poor outcome. In multivariate analysis, only high NRS was an independent risk factor for 90-day survival rate in patients with MTB. A high nutritional risk score was a good predictor of poor outcome in miliary tuberculosis patients. Additional approaches to recover the nutritional deficits may become a focus in future management of miliary tuberculosis.

High-Sensitivity C-Reactive Protein Levels and Cancer Mortality

Background: High-sensitivity C-reactive protein (hs-CRP) is an important inflammatory marker, and inflammation is known to be involved in the initiation and progression of cancer. We investigated the association between serum hs-CRP levels and all-cause mortality, cancer mortality, and site-specific cancer mortality in apparently cancer-free Koreans. Methods: A total of 33,567 participants who underwent routine check-ups at a single tertiary hospital health-screening center between May 1995 and December 2006, and whose serum hs-CRP level data were available, were included in the study. Baseline serum hs-CRP levels were obtained and subjects were followed up for mortality from baseline examination until December 31, 2008. Results: During an average follow-up of 9.4 years, 1,054 deaths, including 506 cancer deaths, were recorded. The adjusted HRs (aHR; 95% confidence interval [CI]) of subjects with hs-CRP ≥3 mg/L for all-cause and cancer-related mortality were 1.38 (1.15–1.66) and 1.61 (1.25–2.07) in men, and 1.29 (0.94–1.77) and 1.24 (0.75–2.06) in women, respectively, compared with subjects with hs-CRP ≤1 mg/L. Elevated hs-CRP was also associated with an increased risk of site-specific mortality from lung cancer for sexes combined (2.53 [1.57–4.06]). Conclusions: This study suggests that elevated levels of hs-CRP in apparently cancer-free individuals may be associated with increased mortality from all-causes and cancer, in particular, lung cancer in men, but not in women. Impact: As a marker for chronic inflammation, hs-CRP assists in the identification of subjects with an increased risk of cancer death. Cancer Epidemiol Biomarkers Prev; 21(11); 2076–86. ©2012 AACR.

Renal Hyperfiltration as a Novel Marker of All-Cause Mortality

Although renal hyperfiltration (RHF) or an abnormal increase in GFR has been associated with many lifestyles and clinical conditions, including diabetes, its clinical consequence is not clear. RHF is frequently considered to be the result of overestimating true GFR in subjects with muscle wasting. To evaluate the association between RHF and mortality, 43,503 adult Koreans who underwent voluntary health screening at Seoul National University Hospital between March of 1995 and May of 2006 with baseline GFR≥60 ml/min per 1.73 m(2) were followed up for mortality until December 31, 2012. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and RHF was defined as GFR>95th percentile after adjustment for age, sex, muscle mass, and history of diabetes and/or hypertension medication. Muscle mass was measured with bioimpedance analysis at baseline. During the median follow-up of 12.4 years, 1743 deaths occurred. The odds ratio of RHF in participants with the highest quartile of muscle mass was 1.31 (95% confidence interval [95% CI], 1.11 to 1.54) compared with the lowest quartile after adjusting for confounding factors, including body mass index. The hazard ratio of all-cause mortality for RHF was 1.37 (95% CI, 1.11 to 1.70) by Cox proportional hazards model with adjustment for known risk factors, including smoking. These data suggest RHF may be associated with increased all-cause mortality in an apparently healthy population. The possibility of RHF as a novel marker of all-cause mortality should be confirmed.

Exposure to volatile organic compounds and loss of pulmonary function in the elderly

Volatile organic compounds (VOCs) are reported to cause adverse effects on pulmonary function in occupationally exposed workers. However, evidence is lacking on the effect in the general population. We hypothesised that VOCs impair pulmonary function through enhancing oxidative stress, especially in the elderly population. A longitudinal panel study of 154 elderly people was performed in South Korea. Repeated spirometric tests were performed up to eight times on different days for each subject. We also measured urinary concentrations of metabolites of the VOC and markers of oxidative stress (malondialdehyde and 8-oxo-2′-deoxyguanosine) on the same day of spirometric tests. A mixed linear regression model was used to evaluate the association among the VOC metabolites, oxidative stress markers and spirometric tests. We found that the urinary levels of hippuric acid and methylhippuric acid, which are metabolites of toluene and xylene, respectively, were significantly associated with reduction of forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), and forced expiratory flow at 25–75% of FVC. We also found significant associations between the metabolites of VOCs and the markers of oxidative stress. In addition, the oxidative stress markers were associated with pulmonary function parameters. This study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.

Medical big data: promise and challenges

The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

Association of cold ambient temperature and cardiovascular markers.

Cardiovascular mortality has been shown to increase in the winter. However, it is unclear whether cold temperature affects indicators known as cardiovascular markers. We evaluated the association between ambient temperature and cardiovascular markers using data collected retrospectively from 55,567 adults who had visited a health check-up clinic between 1995 and 2008. Non-parametric smoothing regressions were fitted to determine the shapes of association between temperature and cardiovascular markers such as blood pressure, lipid profiles, platelet count, and high sensitivity C-reactive protein (hsCRP). Mixed effect model was used to investigate the significance of the relationship between temperature and cardiovascular markers. Decreased ambient temperature was associated with an increase in systolic and diastolic blood pressures, platelet count and serum low density lipoprotein-cholesterol concentration. In contrast, high density lipoprotein-cholesterol level declined with decreasing temperature. The hsCRP level increased with decreasing temperature in the minimum temperatures below 0°C, but revealed a reverse association above. Our study suggests that excess cardiovascular mortality in cold weather might be associated with temperature-related variations of cardiovascular markers.

EBUS-TBNA in the differential diagnosis of pulmonary artery sarcoma and thromboembolism

To the Editors: Pulmonary artery sarcoma is a rare tumour of the cardiovascular system. It is often misdiagnosed as acute or chronic pulmonary thromboembolism because its clinical presentation and radiological findings are similar to those of thromboembolism. The diagnosis of pulmonary artery sarcoma by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has not been reported. Herein, we report two cases with mass-like lesion in the pulmonary artery. The lesions were safely approached by EBUS-TBNA, and the tissues obtained by EBUS-TBNA were sufficient to diagnose pulmonary artery sarcoma and thromboembolism. A 79-yr-old female with hypertension and atrial fibrillation presented with sudden-onset left chest and shoulder pain. She had taken warfarin for atrial fibrillation, but the warfarin had been discontinued for 1 week because of a scheduled endoscopy. We performed chest computed tomography (CT), which revealed an extensive intraluminal low-attenuated mass- like lesion involving the entire luminal diameter of the left main and left lower lobar pulmonary artery (fig. 1a). d-dimer was 0.94 μg·mL−1 (reference value <0.4 μg·mL−1). Positron emission tomography (PET)-CT with 18F-fluorodeoxyglucose (FDG) showed increased FDG uptake, with a maximum standardised uptake value (SUV max) of 18.6 in the left main pulmonary artery (fig. 1c). For a tissue diagnosis, EBUS-TBNA was performed targeting the mass-like lesion encasing the pulmonary artery (fig. 1d). The sonograph revealed a round heterogeneous mass with distinct margin that include some necrotic area. The cytopathological examination confirmed spindle cell malignancy with vimentin …

The differential effect of cigarette smoking on glomerular filtration rate and proteinuria in an apparently healthy population

The detrimental effects of cigarette smoking on the kidney in healthy individuals without established renal diseases have not been established. We evaluated the effects of smoking on renal function and proteinuria in 35 288 apparently healthy participants who were not on antihypertensive and/or antidiabetic medication and who had undergone a health examination at the Health Promotion Center, Seoul National University Hospital from 1995 to 2006. Renal function was estimated using the simplified Modification of Diet in Renal Disease Study equation for estimated glomerular filtration rate (eGFR), and proteinuria was determined by the spot urine dipstick test. Adjusted eGFR was higher in current smokers (mean±s.e.m., 79.3±0.1 ml min−1) than in ex-smokers (77.3±0.2 ml min−1, P<0.001) and non-smokers (77.7±0.1 ml min−1, P<0.001). The adjusted eGFR of smokers who smoked >20 cigarettes per day were higher than that of individuals who smoked ⩽20 cigarettes per day (P<0.001). In participants with an eGFR of <50 ml min−1, current smoking (38.3±1.9 ml min−1) and past smoking (39.5±1.9 ml min−1) were associated with significantly lower eGFR values than non-smoking (45.1±1.2 ml min−1; P=0.007 and P=0.027, respectively). Current smoking was associated with a higher risk of proteinuria (urine dipstick for albuminuria ⩾1+) than non-smoking (odds ratio=1.380, P<0.001). In conclusion, cigarette smoking is associated with a higher eGFR in the general population, whereas it might reduce eGFR in a small subset of the population and increase the risk of proteinuria. These subsets should be better defined to prevent chronic kidney diseases related to smoking in the general population.

Association between the markers of metabolic acid load and higher all-cause and cardiovascular mortality in a general population with preserved renal function

Although metabolic acid load has been associated with many well-known risk factors for mortality, its clinical implications are not yet clear. To evaluate the association between biomarkers of metabolic acid load, such as serum bicarbonate, serum anion gap and urine pH and mortality, we analyzed the health records of 31 590 adults who underwent a health screening between January 2001 and December 2010 and had an estimated glomerular filtration rate ⩾60 ml min−1 per 1.73 m2. Urine pH was measured by a dipstick test performed on fast morning urine sample and categorized as acidic (urine pH ⩽5.5), neutral and alkaline (urine pH ⩾8.0). Using the Cox proportional hazard model, the adjusted hazard ratio (aHR) of all-cause mortality of the lowest quartile of serum bicarbonate was 1.460 (95% confidence interval (CI) 1.068–1.995) compared with the highest quartile, after a median follow-up of 93 months. The aHRs of cardiovascular and cancer mortality of the lowest quartile of serum bicarbonate were 2.647 (95% CI 1.148–6.103) and 1.604 (95% CI 1.024–2.513), respectively, compared with the highest quartile. Acidic and neutral urine pH were significantly associated with a higher all-cause mortality (aHR 2.550, 95% CI 1.316–4.935; aHR 2.376 95% CI 1.254–4.501, respectively), compared with an alkaline urine pH. In conclusion, higher metabolic acid load was associated with an increased all-cause and cardiovascular mortality in a healthy population. The association between metabolic acid load and mortality and the causality of the relationship need to be confirmed.

Association of Low Aerobic Fitness with Hyperfiltration and Albuminuria in Men

PURPOSE The purpose of this study was to evaluate the association of low aerobic fitness (AF), a quantitative phenotype primarily modified by physical activity, with the earlier markers of chronic kidney disease (CKD). METHODS Maximum oxygen uptake (VO2max), the best index of AF, was estimated in an apparently healthy population of 34,769 adults without known history of diabetes and/or hypertension, and its association with renal function and albuminuria was analyzed retrospectively. VO2max was estimated using a cycle ergometer. Glomerular filtration rate was estimated with the Modification of Diet in Renal Disease Study equation. Glomerular hyperfiltration was defined as estimated glomerular filtration rate above the age- and sex-specific 97.5th percentile. Albuminuria was detected with dipstick urinalysis on fast morning urine and defined as ≥1+. RESULTS VO2max levels were negatively correlated with the odds ratios of glomerular hyperfiltration in men (Ptrend = 0.039), not in women. VO2max was associated with glomerular hyperfiltration in young men (≤ the median age; Ptrend < 0.001), but not in old men. VO2max levels were negatively correlated with the odds ratio of albuminuria in men (Ptrend < 0.001), but not in women. These findings suggest that low AF may be associated with earlier markers of CKD in men. This association was not observed in women. CONCLUSION From the results of this study, it can be concluded that low AF may be a possible independent, modifiable risk factor for CKD in men.