Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

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.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) is dominating coronavirus disease 2019 (COVID-19) worldwide. The waning protective effect of available vaccines against the Omicron variant is a critical public health issue. This study aimed to assess the impact of the third COVID-19 vaccination on immunity against the SARS-CoV-2 Omicron BA.1 strain in older individuals. Materials and Methods: Adults aged ≥60 years who had completed two doses of the homologous COVID-19 vaccine with either BNT162b2 (Pfizer/BioNTech, New York, NY, USA, BNT) or ChAdOx1 nCoV (SK bioscience, Andong-si, Gyeongsangbuk-do, Korea, ChAd) were registered to receive the third vaccination. Participants chose either BNT or mRNA-1273 (Moderna, Norwood, MA, USA, m1273) mRNA vaccine for the third dose and were categorized into four groups: ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273. Four serum specimens were obtained from each participant at 0, 4, 12, and 24 weeks after the third dose (V1, V2, V3, and V4, respectively).Serum-neutralizing antibody (NAb) activity against BetaCoV/Korea/KCDC03/2020 (NCCP43326, ancestral strain) and B.1.1.529 (NCCP43411, Omicron BA.1 variant) was measured using plaque reduction neutralization tests. A 50% neutralizing dilution (ND 50 ) >10 was considered indicative of protective NAb titers. Results: In total, 186 participants were enrolled between November 24, 2021, and June 30, 2022. The respective groups received the third dose at a median (interquartile range [IQR]) of 132 (125 - 191), 123 (122 - 126), 186 (166 -193), and 182 (175 - 198) days after the second dose. Overall, ND 50 was lower at V1 against Omicron BA.1 than against the ancestral strain. NAb titers against the ancestral strain and Omicron BA.1 variant at V2 were increased at least 30-fold (median [IQR], 1235.35 [1021.45 - 2374.65)] and 129.8 [65.3 - 250.7], respectively). ND 50 titers against the ancestral strain and Omicron variant did not differ significantly among the four groups (P= 0.57). NAb titers were significantly lower against the Omicron variant than against the ancestral strain at V3 (median [IQR], 36.4 (17.55 - 75.09) vs. 325.9 [276.07 - 686.97]; P = 0.012). NAb titers against Omicron at V4 were 16 times lower than that at V3. Most sera exhibited a protective level (ND 50 >10) at V4 (75.0% [24/32], 73.0% [27/37], 73.3% [22/30], and 70.6% [12/17] in the ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273 groups, respectively), with no significant differences among groups (P = 0.99). Conclusion A third COVID-19 mRNA vaccine dose restored waning NAb titers against Omicron BA.1. Our findings support a third-dose vaccination program to prevent the waning of humoral immunity to SARS-CoV-2.

Agranulocytosis is a rare but the most serious life-threatening complication of antithyroid drug therapy. Most cases of agranulocytosis occur within the first 3 months of antithyroid drug therapy, but some cases happen several years after starting treatment. However, there is a paucity of data on the delayed onset of agranulocytosis. We report a case of methimazole-induced agranulocytosis with suppurative pharyngotonsillitis occurring during the long-term treatment. A 48-year-old woman with Graves' disease visited our hospital with sore throat and high fever (39.2degrees C). She had continuously been treated with methimazole for the preceding 7 years-15 to 40 mg daily from Jul 2007 until Apr 2014 and 50 mg daily from May 2014 until September 2014. A month ago, the dose of methimazole had been reduced to 10 mg daily due to transient neutropenia. Her initial blood tests showed an absolute neutrophil count of 40/microL. Moreover, physical examination showed right neck enlargement. We stopped methimazole, and she was empirically treated with broad-spectrum antibiotics and granulocyte colony stimulating factor. Neck CT scan detected enlarged right tonsils and lymph node. Cervical lymph node biopsy only showed acute and chronic inflammation. About 3 weeks after she recovered, 10 mCi of radioiodine ablation therapy was performed. This case suggests that the sign of agranulocytosis should be carefully monitored in patients with Graves' disease, throughout the course of treatment with methimazole, even under the long-term therapy.
Agranulocytosis* ; Anti-Bacterial Agents ; Biopsy ; Colony-Stimulating Factors ; Drug Therapy ; Female ; Fever ; Granulocytes ; Graves Disease* ; Hematologic Tests ; Humans ; Inflammation ; Lymph Nodes ; Methimazole ; Middle Aged ; Neck ; Neutropenia ; Neutrophils ; Palatine Tonsil ; Pharyngitis ; Physical Examination ; Tomography, X-Ray Computed

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the CB1 receptor (JWH-073, 081, and 210) and Delta9-tetrahydrocannabinol (Delta9-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. Ki values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed CB1 protein membranes to compare dependence potential with CB1 receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except Delta9-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the CB1 receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.
Animals ; Appointments and Schedules ; Cannabinoids* ; Controlled Substances ; Jurisprudence ; Korea ; Mass Screening ; Membranes ; Mice ; Receptor, Cannabinoid, CB1 ; Rodentia ; Social Problems

BACKGROUND/AIMS: Stomach cancer can be easily diagnosed via endoscopy, but also possible to be missed. The aim of this study was to investigate the clinical and endoscopic characteristics of advanced gastric cancers that were not diagnosed based on endoscopic examination. METHODS: We evaluated patients who had newly diagnosed advanced gastric cancer that was undetected via endoscopy within the last six months. RESULTS: Sixteen patients were included in this study. The locations of the cancers were the cardia in six cases, the greater curvature side of the body in eight cases and the antrum in two cases. The histological findings were tubular type adenocarcinoma in 11 cases, with ten cases of moderately to poorly differentiated adenocarcinoma and five cases of signet ring cell type adenocarcinoma. CONCLUSIONS: Even advanced gastric cancer lesions may not be detected during endoscopy. If a patient continues to complain of upper gastrointestinal symptoms, even though endoscopy does not find abnormal findings, repeated endoscopy and/or additional diagnostic studies should be considered.
Adenocarcinoma/*diagnosis/pathology ; Adult ; Aged ; Cardia/pathology ; Diagnostic Errors ; Female ; Gastroscopy ; Humans ; Male ; Middle Aged ; Prognosis ; Pyloric Antrum/pathology ; Stomach Neoplasms/*diagnosis/pathology

The piriformis syndrome is a condition allegedly attributable to compression of the sciatic nerve by the piriformis muscle. Recently, magnetic resonance neurography and electrophysiologic study have helped to diagnose piriformis syndrome. High dose radiotherapy could induce acute and delayed muscle damage. We had experienced piriformis syndrome with fatty atrophy of piriformis muscle after radiotherapy for recurrent cervical cancer.
Atrophy ; Magnetic Resonance Spectroscopy ; Muscles ; Piriformis Muscle Syndrome ; Sciatic Nerve ; Sciatic Neuropathy ; Uterine Cervical Neoplasms

BACKGROUND/AIMS: Alcoholic hepatitis is an acute or acute-on-chronic inflammatory syndrome associated with significant morbidity and mortality. Traditionally, Maddrey discriminant function (DF) score and Child-Turcott- Pugh (CTP) score have been used for stratifying the prognosis of alcoholic hepatitis. Recently, the model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator for severe alcoholic hepatitis. Therefore, this analysis was aimed to compare MELD score with DF and CTP scores for predicting the short-term mortality in Korean patients with alcoholic hepatitis. METHODS: The medical records of patients hospitalized with alcoholic hepatitis between January 1, 1999 and December 31, 2004 at Hanyang University Guri-Hospital were analyzed retrospectively. RESULTS: Of the 138 medical records reviewed, 74 cases fulfilled the inclusion criteria (61 males and 13 females; mean age 47.1 years). Twelve patients (16.2%) died within 90 days after admission. Univariate analysis demonstrated that variables such as ascites, hepatic encephalopathy, splenomegaly, international normalized ratio, CTP, and DF scores were significantly correlated with increased 90-day mortality while MELD score was not. According to the multivariate analysis, only CTP score was statistically significant (p=0.012) while DF and MELD scores were not significant for predicting 90-day mortality. The survival analysis with Cox regression test showed higher DF and CTP scores, but not MELD score, significantly increased the risk of in-hospital mortality. CONCLUSIONS: This study demonstrates that DF and CTP scores are independent predictors of short-term mortality in patients with alcoholic hepatitis.
Adult ; Female ; Follow-Up Studies ; Hepatitis, Alcoholic/diagnosis/*mortality ; Humans ; Korea ; Liver Diseases/diagnosis/mortality ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; ROC Curve ; *Severity of Illness Index ; Survival Analysis ; Time Factors

In Crohn's disease, neurologic complications such as cerebrovascular accident, headache, peripheral neuropathy have been reported sporadically. The pathogenesis of these neurologic complications is still unknown and controversial. We experienced a 22-year-old man, with Crohn's disease accompanied by optic neuritis. Loss of visual acuity was developed during the worsening course of enterocutaneous fistula. After high dose steroid treatment, his visual acuity and neurologic symptoms improved immediately.
Adult ; Crohn Disease/*complications/drug therapy/pathology ; Humans ; Intestinal Fistula/complications ; Male ; Optic Neuritis/*complications/diagnosis

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is known to be a potent growth inhibitor of many cell types, including most epithelial cells. However, the mechanism of TGF-beta1 action on cell growth in lymphomas and leukemia still remains to be elucidated. c-myc is a central regulator of cell proliferation and apoptosis, and telomerase is believed to play an important role in carcinogenesis. The aim of the study was to determine the effects of cell growth, c-myc gene expression and telomerase activity due to TGF-beta1 and examine its mechanism of action in lymphomas and leukemia. METHODS: The cell growths of Jiyoye (Burkitt lymphoma), H9 (T cell lymphoma), and CCRF-CEM (acute lymphocytic leukemia, T cell) cell lines due to TGF-beta1 were measured using the MTT assay. RT-PCR was also performed to monitor the expression of the c-myc gene in these cells with the telomerase activity measured using a TRAP assay. RESULTS: There was significant inhibition of cell growth in TGF-beta1 (5ng/mL) treated Jiyoye cells. When treated with TGF-beta1, the Jiyoye cells exhibited marked decreases in the levels of c-myc RNA and telomerase activity. However, TGF-beta1 treated H9 and CCRF-CEM cells showed no cell growth inhibition or reductions in the levels of c-myc mRNA and telomerase activity. The effect of TGF-beta1 on cell growth was noted to closely correlate with c-myc mRNA expression and telomerase activity. CONCLUSION: These results suggest that TGF-beta1 may inhibit cell growth in Jiyoye cells by a mechanism involving down-regulation of the c-myc gene, which in turn, reduces the telomerase activity.
Apoptosis ; Carcinogenesis ; Cell Line* ; Cell Proliferation ; Down-Regulation ; Epithelial Cells ; Genes, myc ; Leukemia* ; Leukemia, T-Cell ; Lymphoma* ; RNA ; RNA, Messenger* ; Telomerase* ; Transforming Growth Factor beta1