Long-Term Expansion of Functional Human Pluripotent Stem Cell-Derived Hepatic Organoids

A human cell-based liver model capable of long-term expansion and mature hepatic function is a fundamental requirement for pre-clinical drug development. We previously established self-renewing and functionally mature human pluripotent stem cell-derived liver organoids as an alternate to primary human hepatocytes. In this study, we tested long-term prolonged culture of organoids to increase their maturity. Organoid growing at the edge of Matrigel started to deteriorate two weeks after culturing, and the expression levels of the functional mature hepatocyte marker ALB were decreased at four weeks of culture. Replating the organoids weekly at a 1：2 ratio in fresh Matrigel, resulted in healthier morphology with a thicker layer compared to organoids maintained on the same Matrigel and significantly increased ALB expression until three weeks, although, it decreased sharply at four weeks. The levels of the fetal hepatocyte marker AFP were considerably increased in long-term cultures of organoids. Therefore, we performed serial passaging of organoids, whereby they were mechanically split weekly at a 1：3∼1：5 ratio in fresh Matrigel. The organoids expanded so far over passage 55, or 1 year, without growth retardation and maintained a normal karyotype after long-term cryopreservation. Differentiation potentials were maintained or increased after long-term passaging, while AFP expression considerably decreased after passaging. Therefore, these data demonstrate that organoids can be exponentially expanded by serial passaging, while maintaining long-term functional maturation potential. Thus, hepatic organoids can be a practical and renewable cell source for human cell-based and personalized 3D liver models.

Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Severe Sinus Bradycardia Requiring Cardiac Pacing in a Lupus Patient Who Was Successfully Treated Using Methylprednisolone Pulse Therapy / 대한내과학회지

Symptomatic sinus bradycardia in adults with systemic lupus erythematosus (SLE) is rare. Here, we report a case of severe sinus bradycardia requiring temporary cardiac pacing in a SLE patient successfully treated using methylprednisolone pulse therapy.

Severe Sinus Bradycardia Requiring Cardiac Pacing in a Lupus Patient Who Was Successfully Treated Using Methylprednisolone Pulse Therapy / 대한내과학회지

Symptomatic sinus bradycardia in adults with systemic lupus erythematosus (SLE) is rare. Here, we report a case of severe sinus bradycardia requiring temporary cardiac pacing in a SLE patient successfully treated using methylprednisolone pulse therapy.

Glomerular filtration rate affects interpretation of pulmonary function test in a Korean general population: results from the Korea National Health and Nutrition Examination Survey 2010 to 2012

BACKGROUND/AIMS: The pulmonary abnormalities (principally restrictive abnormalities) are characteristic of renal transplant recipients or those with end-stage renal disease. Our aim was to explore whether the prevalence of spirometric abnormalities was influenced by the estimated glomerular filtration rates (GFRs) in a Korean general population. METHODS: We used data obtained during the 2010 to 2012 Korean National Health and Nutrition Examination Survey, a national cross-sectional survey. We analyzed data from subjects for whom spirometric assays and estimated GFRs were of acceptable quality. RESULTS: A total of 8,809 subjects (3,868 male and 4,941 female) was included. In both males and females with GFR values < 60 mL/min/1.73 m², the linear trends toward the presence of obstructive and restrictive patterns were significant. However, the percent predicted forced vital capacity (FVC) decreased with a decline in the estimated GFR, but only in males (p for trend < 0.0031). Multivariate linear regression analysis showed a decline in the estimated GFR was independently associated with falls in the percent predicted FVC and the forced expiratory volume in 1 second/FVC ratio in both males and females. However, the percent predicted FVC was independently predictive only in males (p = 0.002). CONCLUSIONS: Impaired pulmonary function was associated with a decline in the estimated GFR. The percent predicted FVC decrease paralleled the decline in estimated GFR in male only. Careful interpretation of pulmonary function test data is required in patients with decreased GFRs or impaired renal function, especially males.

Prevalence and risk factors of periodontitis among adults with or without diabetes mellitus

BACKGROUND/AIMS: This study examined prevalence and risk factors of periodontitis in representative samples of Korean adults, with and without diabetes mellitus (DM). METHODS: Data from the 2012 Korean National Health and Nutritional Examination Survey were analyzed. A total of 4,477 adults (≥ 30 years old) were selected from 8,057 individuals who completed a nutrition survey, a self-reported general health behavior questionnaire, an oral examination, an oral hygiene behaviors survey, and laboratory tests. DM was defined as a fasting plasma glucose ≥ 126 mg/dL, or self-reported diagnosed diabetes, or current use of oral hypoglycemic agents and/or insulin. The community periodontal index was used to assess periodontitis status and comparisons between the periodontitis and the non-periodontitis group, were performed, according to the presence of DM. Risk factors for periodontitis in adults with DM and without DM were evaluated by multiple logistic regression analysis. RESULTS: The prevalence of periodontitis was significantly higher in adults with DM (43.7%) than in those without DM (25%, p < 0.001). In adults without DM, risk factors for periodontitis were older age, male, urban habitation, waist circumference, smoking, oral pain, and less frequent tooth brushing. Significant risk factors for periodontitis in adults with DM were the smoking, oral pain, and not-using an oral hygiene product. CONCLUSIONS: Adults with DM have an increased risk of periodontitis than those without DM. Current smoking and oral pain increase this risk. Using an oral hygiene product can reduce risk of periodontal disease in adults with DM.

Disability of Hearing Impairment Is Positively Associated With Urine Albumin/Creatinine Ratio in Korean Adults: The 2011–2012 Korea National Health and Nutrition Examination Survey

OBJECTIVES: The aim of this study was to determine whether chronic kidney disease (CKD) is associated with hearing thresholds in the nationwide, large-scaled Korean population. METHODS: This study analyzed the data of 9,798 subjects of 19 years and older (4,387 males and 5,411 females). Urine albumin-to-creatinine ratio (ACR) was measured from first-voided spot urine samples. The air-conduction hearing threshold was measured at 0.5, 1, 2, 3, 4, and 6 kHz and pure tone audiogram (PTA) average was calculated as the four-frequency average of 0.5, 1, 2, and 4 kHz. RESULTS: Urine ACR was significantly correlated with the PTA average of better ear in both genders, especially at 3 and 6 kHz in males and at 1, 3, 4, and 6 kHz in females. After adjusting, urine ACR also increased the risk of hearing loss in female, especially if urine ACR was 30 mg/g and more (odds ratio, 1.636–2.229. This study showed that the degree of hearing loss was significantly different according to categories of urine ACR in both genders. Hearing loss without disability was found less but that with bilateral hearing disability was found more as urine ACR increased. In generally, prevalence of hearing loss with disability was higher in males than females. CONCLUSION: This study demonstrated that urine ACR was significantly correlated with the PTA average of better ear in Korean adults of both genders. This study suggests that clinicians should carefully monitor the hearing level for subjects with elevated urine ACR, even though high urine ACR within the normal range.

Isolated, Broad-Based Apical Diverticulum: Cardiac Magnetic Resonance Is a "Terminator" of Cardiac Imaging Modality for the Evaluation of Cardiac Apex

In spite of the frequent involvement of many cardiac diseases, it is difficult to evaluate the left ventricular apex in detail with transthoracic echocardiography, a first-line imaging modality in cardiovascular diseases, because the apex is very closely located at the echocardiographic probe. Cardiac magnetic resonance enables us to evaluate the cardiac apex without any limitation to the image acquisition. We here present a case regarding a broad-based apical diverticulum, which was initially confused with apical aneurysm.

A Case of Spontaneous Duodenoileal Fistula in Behcet's Disease / 대한소화기내시경학회지

For intestinal Behcet's disease, the common complications are intestinal perforation, bleeding and fistula formation. Among these, fistula formation is mostly associated with previously performed surgeries and it is rare that fistulas form spontaneously. We experienced a case of Behcet's disease with duodenoileal fistula, and the patient does not have any previous surgery. A 57-year-old male patient was admitted due to persistent diarrhea and weight loss. He was diagnosed with intestinal Behcet's disease 6 years ago. On the 2nd portion of the duodenum, an opening to the colon was found on gastroduodenoscopy. As we rechecked the lesion with performing a gastrograffin upper GI series, there was a fistula between the 2nd portion of the duodenum and ileum. So we performed right hemicolectomy and duodenojejunostomy and we confirmed the duodenoileal fistula. Overall, we would like to suggest that this case was a case of Behcet's disease with spontaneous duodenoileal fistula.

The Difference of Left Ventricular Hypertrophy and the Diastolic Function between Prehypertensives and Normotensives

BACKGROUND AND OBJECTIVES: We investigated whether prehypertensives (PHs) exhibit more prevalent electrocardiographic and echocardiographic left ventricular hypertrophy (ECG LVH) and if they are are more associated with impaired left ventricular (LV) diastolic function than are normotensives (NTs). SUBJECTS AND METHODS: A total of 608 subjects> or = 40 years of age with normal BP (SBP<120 mmHg and DBP<80 mmHg, n=335) and PH (n=273) and who were without a history of hypertension, diabetes and any other known cardiovascular diseases underwent blood sampling for obtaining the lipid profile, and they also underwent 12-lead electrocardiography and echocardiography. RESULTS: Compared with the NTs, the PHs had significantly higher Sokolow-Lyon and Cornell voltage for ECG LVH, and they ahd a higher prevalence of ECG LVH (men: 16.9% vs 5.9%, women: 2.0% vs 1.0%, respectively). The PHs had a more increased left ventricular mass index (LVMI, Men: 118.1+/-24.4 g/m2 vs 102.0+/-19.1 g/m2, p=0.02; Women: 117.5+/-26.4 g/m2 vs 101.9+/-30.7 g/m2, p=0.02) and a more decreased LV diastolic function (E/A, Men: 1.14+/-0.6 vs 1.30+/-0.4, p=0.03; Wemen: 1.11+/-0.6 vs 1.25+/-0.5, p=0.03) on echocardiography than the NTs. CONCLUSION: The PHs were associated with a higher prevalence of ECG LVH and a more increased LVMI on echocardiography than that of the NTs. Therefore, we should pay earlier attention to diagnose and screen the pre-hypertensive group.

Risk of Postoperative Infection in Patients with Inflammatory Bowel Disease / 대한소화기학회지

BACKGROUND/AIMS: The clinical course of patients with inflammatory bowel disease (IBD) frequently leads to the use of immunosuppressants and immunomodulators. We investigated the risk of postoperative infection in patients with IBD undergoing elective bowel surgery and whether the use of corticosteroid (CS) and/or 6-mercaptopurine/ azathioprine (6-MP/AZA) before surgery was associated with the increased risk of postoperative infection. METHODS: Patients who were diagnosed as Crohn's disease (n=25) or ulcerative colitis (n=19) and underwent elective bowel surgery between 1986 and 2005 were identified. Medical records were retrospectively analyzed including age, sex, duration of disease, indication for surgery, duration of surgery, type of surgery, type of postoperative infection, admission period, usage of CS and 6-MP/AZA, and preoperative laboratory values. There were 27 patients receiving CS alone, 6 patients receiving 6-MP/AZA alone or with CS, and 16 patients receiving neither CS nor 6-MP/AZA. RESULTS: There were 17 postoperative infections (38.6%) among IBD patients who had undergone surgery and wound infection was the most common type of infection (76.5%). In IBD patients, patients receiving CS had higher postoperative infection rate than those patients receiving neither CS nor 6-MP/AZA (p=0.039). Patients receiving CS in conjunction with 6-MP/AZA did not have significantly higher postoperative infection rate than those with CS only (p=0.415). CONCLUSIONS: Preoperative use of CS in patients with IBD is associated with the increased risk of postoperative infections. Addition of 6-MP/AZA in patients receiving CS does not increase the risk of postoperative infections.