Hong Sang Choi

Value of Early Risk Stratification Using Hemoglobin Level and Neutrophil-to-Lymphocyte Ratio in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Complete blood count is the most widely available laboratory datum in the early in-hospital period after ST-elevation myocardial infarction (STEMI). We assessed the clinical utility of the combined use of hemoglobin (Hb) level and neutrophil-to-lymphocyte ratio (N/L) for early risk stratification in patients with STEMI. We analyzed 801 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) within 12 hours of onset of symptoms. Patients with cardiogenic shock or underlying malignancy were excluded, and 739 patients (63 ± 13 years, 74% men) were included in the final analysis. Patients were categorized into 3 groups using the median value of N/L (3.86) and the presence of anemia (Hb <13 mg/dl in men and <12 mg/dl in women); group I had low N/L and no anemia (n = 272), group II had low N/L and anemia, or high N/L and no anemia (n = 331), and group III had high N/L and anemia (n = 136). There were significant differences on clinical outcomes during 6-month follow-up among the 3 groups. Prognostic discriminatory capacity of combined use of Hb level and N/L was also significant in high-risk subgroups such as patients with advanced age, diabetes mellitus, multivessel coronary disease, low ejection fraction, and even in those having higher mortality risk based on Thrombolysis In Myocardial Infarction risk score. In a Cox proportional hazards model, after adjusting for multiple covariates, group III had higher mortality at 6 months (hazard ratio 5.6, 95% confidence interval 1.1 to 27.9, p = 0.036) compared to group I. In conclusion, combined use of Hb level and N/L provides valuable timely information for early risk stratification in patients with STEMI undergoing primary PCI.

Usefulness of cardiac biomarkers in the prediction of right ventricular dysfunction before echocardiography in acute pulmonary embolism

BACKGROUND The aim of this study was to investigate a useful cardiac biomarker for predicting echocardiographic right ventricular (RV) dysfunction in patients with acute pulmonary embolism (APE). METHODS A total of 84 patients with APE were divided into two groups: patients with RV dysfunction (group I, n=51, 61.8 ± 15.1 years) versus without RV dysfunction (group II, n=33, 66.8 ± 13.6 years). Cardiac biomarkers were compared between the groups. RESULTS The level of N-terminal pro-brain-type natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnt), and I (cTni) was significantly elevated in group I compared to group II, but the level of creatine kinase and high-sensitivity C-reactive protein was not different. By receiver operating characteristic curve analysis, the area under the curve to predict RV dysfunction was 0.912 for NT-proBNP, 0.797 for cTnt, and 0.766 for cTni. The optimal cut-off value to predict RV dysfunction was 620.0 pg/mL for NT-proBNP (sensitivity: 90.2%, specificity: 75.8%), 0.016 ng/mL for cTnt (sensitivity: 82.4%, specificity: 78.8%), and 0.055 ng/mL for cTni (sensitivity: 86.3%, specificity: 66.7%). NT-proBNP > 620 pg/mL and cTnt > 0.016 ng/mL were independent predictors of RV dysfunction on multivariate analysis after adjustment for the baseline characteristics. CONCLUSIONS NT-proBNP, cTnt, and cTni were significant serologic predictors of RV dysfunction in APE. Measurements of NT-proBNP, cTnt, and cTni are simple and useful in the risk stratification or treatment of APE.

Farnesoid X Receptor Ligand Prevents Cisplatin-Induced Kidney Injury by Enhancing Small Heterodimer Partner

The farnesoid X receptor (FXR) is mainly expressed in liver, intestine and kidney. We investigated whether 6-ethyl chenodeoxycholic acid (6ECDCA), a semisynthetic derivative of chenodeoxycholic aicd (CDCA, an FXR ligand), protects against kidney injury and modulates small heterodimer partner (SHP) in cisplatin-induced kidney injury. Cisplatin inhibited SHP protein expression in the kidney of cisplatin-treated mice and human proximal tubular (HK2) cells; this effect was counteracted by FXR ligand. Hematoxylin and eosin staining revealed the presence of tubular casts, obstructions and dilatations in cisplatin-induced kidney injury, which was attenuated by FXR ligand. FXR ligand also attenuated protein expression of transforming growth factor-β1 (TGF-β1), Smad signaling, and the epithelial-to-mesenchymal transition process, inflammatory markers and cytokines, and apoptotic markers in cisplatin-treated mice. Cisplatin induced NF-κB activation in HK2 cell; this effect was attenuated by pretreatment with FXR ligand. In SHP knockdown by small interfering RNA, cisplatin-induced activation of TGF-β1, p-JNK and Bax/Bcl-2 ratio was not attenuated, while SHP overexpression and FXR ligand inhibited expression of these proteins in cisplatin-pretreated HK2 cells. In conclusion, FXR ligand, 6ECDCA prevents cisplatin-induced kidney injury, the underlying mechanism of which may be associated with anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through SHP induction.

Clinical outcomes of acute myocardial infarction with occluded left circumflex artery

Left circumflex artery (LCX) related acute myocardial infarction (AMI) has been known to be under diagnosed with 12-lead electrocardiogram (ECG). However, there were only a few studies that have focused on the clinical characteristics of LCX-related AMI. We studied the clinical characteristics and hospital mortality in patients with angiographically confirmed LCX-related AMI. A total of 2281 AMI patients with single acutely occluded culprit vessel in coronary angiography (pre-Thrombolysis In Myocardial Infarction flow: 0) were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to January 2008. These patients were divided into three groups according to culprit vessel [left anterior descending artery (LAD), right coronary artery (RCA), and LCX]. This study showed the patients with LCX-related AMI were less likely to present with ST elevation in ECG (46.3%, 87.0%, and 82.3%; p<0.001) and primary percutaneous coronary intervention (PCI) (43.4%, 78.9%, and 74.5%; p<0.001) and door to balloon time <90 min (31.3%, 52.8%, and 51.0%; p<0.001), compared with LAD and RCA. However, no statistical difference was found in hospital mortality among the three groups. Multivariate analysis showed primary PCI decreased the hospital mortality in patients with occluded coronary artery. In conclusion, AMI patients with an occluded LCX presented with less ST elevation and primary PCI. These results suggest that clinical physicians should be careful with patients presenting with chest pain but apparently normal ECG and must rule out LCX occlusion.

Impact of Acute Kidney Injury on Clinical Outcomes after ST Elevation Acute Myocardial Infarction.

Purpose This study aimed to compare the incidence and clinical significance of transient versus persistent acute kidney injury (AKI) on acute ST elevation myocardial infarction (STEMI). Materials and Methods The study was a retrospective cohort of 855 patients with STEMI. AKI was defined as an increase of ≥0.3 mg/dL in creatinine level at any point during hospital stay. The study population was classified into 5 groups: 1) patients without AKI; 2) patients with mild AKI that was resolved by discharge (creatinine change less than 0.5mg/dL compared with admission creatinine during hospital stay, transient mild AKI); 3) patients with mild AKI that did not resolve by discharge (persistent mild AKI); 4) patients with moderate/severe AKI that was resolved by discharge (creatinine change more than 0.5 mg/dL compared with admission creatinine, transient moderate/severe AKI); 5) patients with moderate/severe AKI that did not resolve by discharge (persistent moderate/severe AKI). We investigated 1-year all-cause mortality after hospital discharge for the primary outcome of the study. The relation between AKI and 1-year mortality after STEMI was analyzed. Results AKI occurred in 74 (8.7%) patients during hospital stay. Adjusted hazard ratio for mortality was 3.139 (95% CI 0.764 to 12.897, p=0.113) in patients with transient, mild AKI, and 8.885 (95% CI 2.710 to 29.128, p<0.001) in patients with transient, moderate/severe AKI compared to patients without AKI. Persistent moderate/severe AKI was also independent predictor of 1 year mortality (hazard ratio, 5.885; 95% CI 1.079 to 32.101, p=0.041). Conclusion Transient and persistent moderate/severe AKI during acute myocardial infarction is strongly related to 1-year all cause mortality after STEMI.

Very Late Stent Thrombosis in a Drug-Eluting Stent due to Interruption of Anti-Platelet Agents in Patients With Acute Myocardial Infarction and Thrombocytosis

Stent thrombosis is a fatal complication in patients who have undergone percutaneous coronary intervention, and discontinuation of anti-platelet agent is a major risk factor of stent thrombosis. We report a rare case of very late stent thrombosis (VLST) following discontinuation of anti-platelet agents in a patient who experienced acute myocardial infarction and essential thrombocytosis. She had undergone implantation of a drug eluting stent (DES) and a bare metal stent (BMS) two and half years prior to her presentation. VLST developed in DES, not in BMS, following interruption of anti-platelet therapy.

Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease

Tubulointerstitial fibrosis is a common feature of kidney disease. Histone deacetylase (HDAC) inhibitors have been reported to attenuate renal fibrosis progression. Here, we investigated the effect of CG200745, a novel HDAC inhibitor, on renal fibrosis development in a mouse model of unilateral ureteral obstruction (UUO). To examine the effects of CG200745 on renal fibrosis in UUO, C57BL/6 J male mice were divided into three groups: control, UUO, and CG200745 (30 mg/kg/day)-treated UUO groups. CG 200745 was administered through drinking water for 1 week. Human proximal tubular epithelial (HK-2) cells were also treated with CG200745 (10 µM) with or without TGF-β (2 ng/mL). Seven days after UUO, plasma creatinine did not differ among the groups. However, plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were markedly increased in the UUO group, which were attenuated by CG200745 treatment. UUO kidneys developed marked fibrosis as indicated by collagen deposition and increased α-smooth muscle actin (SMA) and fibronectin expression. CG200745 treatment attenuated these fibrotic responses and suppressed UUO-induced production of transforming growth factor-beta1 (TGF-β) and phosphorylation of Smad-2/3. CG200745 treatment also attenuated UUO-induced inflammation as indicated by the expression of inflammatory markers. Furthermore, CG200745 attenuated phosphorylation of p38 mitogen-activated protein kinase in UUO kidneys. In HK-2 cells, TGF-β induced the expression of α-SMA and fibronectin, which were attenuated by CG200745 cotreatment. These results demonstrate that CG200745, a novel HDAC inhibitor, has a renoprotective effect by suppressing renal fibrosis and inflammation in a UUO mouse model.

Tumor necrosis factor α-converting enzyme inhibitor attenuates lipopolysaccharide-induced reactive oxygen species and mitogen-activated protein kinase expression in human renal proximal tubule epithelial cells

Tumor necrosis factor-α (TNFα) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which TNFα-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS (10 µg/ml) in the presence or absence of a type 1 TACE inhibitor (1 µM) or type 2 TACE inhibitor (10 µM). LPS treatment induced increased serum creatinine, TNFα, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

Impact of random urine proteinuria on maternal and fetal outcomes of pregnancy: a retrospective case-control study

Background/Aims Proteinuria is associated with hypertension and preeclampsia in pregnancy. However, the impact of random urine proteinuria on fetal and maternal outcomes has not been established. We investigated the influence of random urine proteinuria on the clinical outcomes of pregnancy. Methods From January 2008 to December 2010, 2,822 patients were retrospectively studied. A total of 536 pregnant women with proteinuria in random urine and matched controls without proteinuria via propensity score matching were analyzed. Proteinuria was checked by the dipstick method. Results The patients’ mean age was 33.0 ± 4.7 years, and the mean gestational age was 235.6 ± 50.6 days on admission. The prevalence of hypertension and chronic kidney disease was 2.4% (n = 67) and 1.0% (n = 29), respectively. Women with random urine proteinuria showed higher blood urea nitrogen levels and a higher incidence of hematuria. These women also had a higher incidence of preeclampsia, preterm labor, premature rupture of membranes, and intrauterine growth restriction. Proteinuria was strongly correlated with preeclampsia in both propensity score matching (p < 0.001, r = 0.783) and unmatched whole samples (p < 0.001, r = 0.851). Conclusions These findings suggest that random urine proteinuria is associated with preeclampsia, preterm labor, premature rupture of membrane, and intrauterine growth restriction.

Transient rotation of the right kidney

A 30-year-old woman visited our hospital for kidney enlargement in computed tomography (CT). She had been treated with antibiotics for acute pyelonephritis at local hospital. Findings from a physical examination were unremarkable, except for right costovertebral angle tenderness. Since beginning antibiotic treatment at her primary care hospital 2 days previously, her flank pain and fever had improved. Initial laboratory test results at our hospital showed a white blood cell count of 8700 cells/ mm, a C-reactive protein (CRP) level of 13.28 mg/dL, and a urinary white blood cell count of 0–1 per high power field. Her CT image showed right kidney enlargement (Fig. 1b). We compared CT images with her previous CT scan (Fig. 1a). On her past CT scan, the right kidney was nearly parallel to the right psoas muscle. On recent CT scan, however, the right kidney was rotated around its short axis, with the long axis laying more toward the horizontal plane (Fig. 2a). After recovery from pyelonephritis, we performed follow-up abdominopelvic CT, which showed that her right kidney had returned to its original position (Fig. 2b). Acquired rotation of the kidney is incidentally detected on imaging studies performed due to other diseases. It can be caused by the enlargement of organs around the kidney or space-occupying lesions in the abdominal cavity. In previously reported similar case [1], transient kidney rotation was thought to be due to transient hepatomegaly and passive renal congestion secondary to pulmonary embolism. However, the patient in our case did not have hepatomegaly or other space-occupying lesions around the kidney. We thought that the mild enlargement associated with acute pyelonephritis may have caused her kidney rotation.