Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Multifocal papillary thyroid carcinoma (mPTC) comprises about 20-30% of PTC. In mPTC, individual tumor foci can be identical or frequently composed of different histological types including follicular, solid, tall-cell or conventional patterns. We report a case of mPTC consisting of one encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) and three conventional PTCs in a 44-year-old woman. This case genetically demonstrates unique features including the simultaneous presence of the BRAF V600E (T1799A) mutation and the BRAF K601E (A1801G) mutation in conventional PTC and FVPTC, respectively.
Carcinoma ; Carcinoma, Papillary ; Factor IX ; Female ; Humans ; Thyroid Gland ; Thyroid Neoplasms

BACKGROUND/AIMS: The symptoms of inflammatory bowel disease (IBD) fluctuate considerably over time. However, it has not been determined whether these symptoms are affected by the menstrual cycle in female IBD patients. This study analyzed the effects of the menstrual cycle on IBD symptom variation. METHODS: This was a prospective study of 91 study subjects (47 IBD patients and 44 healthy controls) who reported daily symptoms and signs throughout their menstrual cycles. RESULTS: IBD patients had significantly more frequent gastrointestinal symptoms, such as nausea (30% vs 7%, p=0.006), flatulence (53% vs 22%, p=0.003), and abdominal pain as compared to controls (68% vs 38%, p=0.006). The IBD patients also experienced more frequent systemic premenstrual symptoms than the controls (79% vs 50%, p=0.003). More severe abdominal pain (p=0.002) and lower mean general condition scores (p=0.001) were noted during the menstrual phase as compared to the pre- or post-menstrual phase in both groups. IBD patients experienced more frequent premenstrual gastrointestinal symptoms than controls, but their IBD symptoms did not change significantly during the menstrual cycle. CONCLUSIONS: Knowledge of the cyclic alterations in gastrointestinal and systemic symptoms may be helpful in determining the true exacerbation of disease in female IBD patients.
Abdominal Pain ; Female ; Flatulence ; Humans ; Inflammatory Bowel Diseases ; Menstrual Cycle ; Nausea ; Prospective Studies

BACKGROUND: Recently, liquid-based cytology (LBC) has been introduced as an alternative to the conventional smear (CS) technique in thyroid fine needle aspiration, due to its diagnostic convenience. METHODS: We assessed 77 cases of thyroid fine needle aspiration using the SurePath(TM) method (SP) as LBC and CS via split-sample techniques. BRAF mutation tests were carried out via polymerase chain reaction and pyrosequencing immediately after diagnosis or a delay of more than one year. RESULTS: In a comparison between SP and CS, the rate of concordance between SP and CS was as high as 84.4% (kappa value, 0.754). In comparison with histologic diagnosis, the overall sensitivity was 100% for both. The specificity was 62.5% for SP and 56.3% for CS. Relative to CS, papillary carcinomas on SP slides revealed more accentuated nuclear irregularities, nucleoli, and reduced nuclear size. In contrast to CS, the delayed BRAFV600E mutation test using SP slides after 1-2 years failed. The use of new primers amplifying shorter product size could help the delayed test achieve success. CONCLUSIONS: Differences in the diagnostic efficacy of SP and CS were negligible. The failure of the delayed BRAF mutation test on the SP slides might be associated with DNA degradation.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; DNA ; Needles ; Polymerase Chain Reaction ; Sensitivity and Specificity ; Thyroid Gland

BACKGROUND: Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity. METHODS: We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x). RESULTS: Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score. CONCLUSIONS: The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.
B-Lymphocytes ; Humans ; L-Lactate Dehydrogenase ; Lymphocytes, Tumor-Infiltrating ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, Large B-Cell, Diffuse ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer

BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is currently the most promising predictive marker for the outcome and benefit from temozolomide treatment in patients with glioblastoma, but there is no consensus on the analysis method for assessing the methylation status in the molecular diagnostic field. The objective of this study was to evaluate methylation-specific polymerase chain reaction (MSP) and pyrosequencing methods for assessing MGMT gene promotor methylation of glioblastoma as well as assessing the MGMT protein expression by immunohistochemistry. METHODS: Twenty-seven cases of glioblastoma from the archives at the Department of Pathology Konkuk University Hospital were selected. MGMT promoter methylation was evaluated by MSP and the pyrosequencing methods. The MGMT expression was also measured at the protein level by immunohistochemistry. RESULTS: Overall, MGMT hypermethylation was observed in 44.4% (12/27 cases) of the case of glioblastoma using either MSP or pyrosequencing. The concordant rate was 70.3% (19/27 cases) between MSP and pyrosequencing for MGMT methylation. There was no correlation between MGMT methylation and the protein expression. No significant differences in progression free survival and overall survival were seen between the methylated group and the unmethylated group by using either MSP or pyrosequencing. The status of the MGMT protein expression was correlated with progression free survival (p=0.026). CONCLUSIONS: In this study the concordance rate between MSP and the pyrosequencing methods for assessing MGMT gene promotor methylation was relatively low for the cases of glioblastoma. This suggests that more reliable techniques for routine MGMT methylation study of glioblastoma remain to be developed because of quality control and assurance issues.
Consensus ; Dacarbazine ; Disease-Free Survival ; DNA Modification Methylases ; DNA Repair Enzymes ; Glioblastoma ; Humans ; Methylation ; Pathology, Molecular ; Polymerase Chain Reaction ; Quality Control ; Tumor Suppressor Proteins

Sheehan's syndrome has been attributed to ischemic damage of the pituitary gland or hypothalamic-pituitary stalk during the peripartum period. Well-described clinical features of Sheehan`s syndrome include hypothyroidism, growth hormone deficiency, hypogonadism, hypoprolactinemia, adrenal insufficiency, and different sodium and water disturbance. The occurrence of sodium and water disturbances associated with Sheehan`s syndrome depends on the degree of pituitary damage, time of onset since the initial pituitary insult, and concurrent medical conditions that also may play a role in sodium and water balance. Chronic hyponatremia is the most common presentation of altered sodium levels in patients with Sheehan`s syndrome. The chronic nature of the presenting hyponatremia suggests more subtle changes of panhypopituitarism or better adaptive mechanism. Although controversial, another mechanism proposed for hyponatremia in the chronic setting involves alternation in the renin-angiotensin/aldosterone system with resulting sodium wasting. We presented a patient with Sheehan`s syndrome associated with hyporeninemic hypoaldosteronism and hyponatremia 53 years old women, who had 4th baby delivery with severe blood loss about 25 years ago, was admitted to hospital because of general weakness. The patient was diagnosis Sheehan`s syndrome with hyponatremia. In addition, we performed hormonal study to find cause of hyponatremia. The results were hypopituitarism and hyporeninemic hypoaldosteronism. Hyponatremia was corrected by hormonal therapy (glucocorticoid,synthyroid,estrogen). The patient felt well-being sensation and was followed up the out-patient department.
Adrenal Insufficiency ; Diagnosis ; Female ; Growth Hormone ; Humans ; Hypoaldosteronism ; Hypogonadism ; Hyponatremia* ; Hypopituitarism* ; Hypothyroidism ; Middle Aged ; Outpatients ; Peripartum Period ; Pituitary Gland ; Sensation ; Sodium