Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia

OBJECTIVES: We compared vascular and metabolic responses (and adverse responses) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia. BACKGROUND: The mechanisms of action for statins and fibrates are distinct. METHODS: Fifty-six patients were given atorvastatin 10 mg and placebo, atorvastatin 10 mg and fenofibrate 200 mg, or fenofibrate 200 mg and placebo daily during each two-month treatment period of a randomized, double-blind, placebo-controlled crossover trial with two washout periods of two months' each. RESULTS: Lipoproteins were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone. Flow-mediated dilator response to hyperemia and plasma high-sensitivity C-reactive protein and fibrinogen levels were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone (p < 0.001, p = 0.182, and p = 0.015 by analysis of variance [ANOVA], respectively). The effects of combined therapy or fenofibrate alone on plasma adiponectin levels and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) were significantly greater than those of atorvastatin alone (p = 0.022 for adiponectin and p = 0.049 for QUICKI by ANOVA). No patients were withdrawn from the study as the result of serious adverse effects. CONCLUSIONS: Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia.     

Fibrinogen Seoul (FGG Ala341Asp): a novel mutation associated with hypodysfibrinogenemia.

Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in fibrinogen function. The molecular basis of hypodysfibrinogenemia was investigated in a 66-year-old woman with peripheral artery obstructive disease and in her family members. Plasma level of functional fibrinogen determined using the Clauss method was lower (75 mg/dL; normal, 140-460 mg/dL) than that measured with immunologic nephelometric assay (137 mg/dL; normal, 180-400 mg/dL). Similar results were also observed in two family members through two generations. DNA was extracted from whole blood, and the coding regions and intron/exon boundaries of gamma chain gene (FGG) were amplified. A novel (Fibrinogen Seoul) heterozygous FGG mutation (GCT->GAT, Ala341Asp) was identified in all three affected family members. Thrombin-catalyzed polymerization was found to be defective on the analysis of purified fibinogen from the propositus. Molecular modeling also showed a conformational change of fibrinogen structure.     

Profiles of IgE Sensitization to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f 20 in Korean House Dust Mite Allergy Patients

Purpose

Measurement of IgE specific to purified house dust mite (HDM) allergens may improve allergy diagnosis. This study aimed to investigate the sensitization profiles of Korean HDM allergic subjects suffering from respiratory allergy and atopic dermatitis (AD) to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f 20.

Methods

Recombinant HDM allergens were produced in Pichia pastoris (Der f 1) or Escherichia coli (5 allergens). IgE reactivity to the individual recombinant allergens and total extract of mite was assessed by ELISA.

Results

Der f 1 was recognized by 79.1%, Der f 2 by 79.1%, Der f 6 by 9.3%, Der f 8 by 6.2%, Der f 10 by 6.2%, and Der f 20 by 6.6% of the patients'' sera tested, while the prevalence of IgE reactivity to total mite extract was 94.7%. Combination of Der f 1 and Der f 2 had a sensitivity of 87.6%. Specific IgE to Der f 2 alone was detected from 89.4% of HDM-sensitized respiratory allergy subjects and 92.3% to the combination of the 2 major allergens Der f 1 and Der f 2. However, sera from fewer patients with AD, namely 72.4% and 71.0%, recognized Der f 1 and Der f 2, respectively. The combination of 2 major allergens allowed diagnosis of 84.5% of the AD patients. No correlation between sensitization to specific allergens and HDM allergy entity was found.

Conclusions

Der f 2 was the most frequently sensitized allergen among the HDM-sensitized respiratory and AD patients in Korea, and the combination of the group 1 and 2 major allergens increased the diagnostic sensitivity. Minor allergens did not significantly improve diagnostic sensitivity. However, further studies are needed to analyze the relationship between sensitization to other HDM allergens and the disease entity of the HDM allergy.     

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.     

Management of choledocholithiasis in an emergency cohort undergoing laparoscopic cholecystectomy: a single-centre experience

Introduction

Minimally-invasive options for the management of choledocholithiasis in patients undergoing laparoscopic cholecystectomy include laparoscopic and endoscopic approaches. This study reviews the effectiveness of both approaches in an emergency setting.

Methods

A retrospective chart review was performed for a cohort of patients who underwent laparoscopic cholecystectomy. Outcomes assessed were duct clearance, the number of procedures performed (NPP), length of stay (LOS) and complication rate.

Results

A total of 182 patients who underwent emergency laparoscopic cholecystectomies received intervention for choledocholithiasis. The duct clearance rate was lower in the laparoscopic group, 63% versus 86% (P = 0.001). However, the median NPP was also lesser in the laparoscopic group, 1 (interquartile range (IQR) 1–2) versus 2 (IQR 2–2) (P < 0.001), as was the median LOS, 5 days (IQR 3–8) versus 7 days (IQR 6–10) (P = 0.009). Forty-eight laparoscopic endobiliary stents were attempted; stent deployment was successful in 37 patients. A larger proportion of patients with laparoscopic endobiliary stents had duct clearance by endoscopic retrograde cholangiopancreatography (ERCP) compared with those without, although this was not statistically significant (P = 0.208).

Conclusion

Laparoscopic clearance is not as effective as post-operative ERCP in an emergency cohort, but is associated with fewer procedures required and a shorter inpatient stay. Thus, laparoscopic clearance may still be an attractive option for surgeons especially where conditions are favourable during an emergency laparoscopic cholecystectomy.     

Long‐term hepatitis B surface antigen (HBsAg) kinetics during entecavir treatment in Korean patients—Functional cure unlikely

The aim of this study was to investigate the on‐treatment kinetics of quantitative HBsAg during entecavir therapy to predict the treatment period needed to achieve functional cure. From a cohort of 1009 CHB treatment‐naïve patients who were started on entecavir, the kinetics of quantitative HBsAg decline was assessed in 410 patients by a linear mixed model. The difference in the kinetics of quantitative HBsAg was determined based on the HBeAg positivity, HBeAg seroclearance and presence of baseline liver cirrhosis. Among the 410 patients, 213 patients (52.0%) were HBeAg‐positive and 217 patients (66.1%) were male with a median age of 48 years. During a median follow‐up of 53.5 months, the quantitative HBsAg level showed a slow but consistent decrease. The expected log qHBsAg levels as a function of time during entecavir treatment in HBeAg(+) and HBeAg(?) patients were 3.4773‐0.0039 × Months and 3.1853‐0.0036 × Months, respectively. The estimated time to clearance of quantitative HBsAg in our study was greater than 74.1 years in HBeAg‐positive patients and 73.5 years in HBeAg‐negative patients. The calculated time to achieve functional cure is lifelong without regard to HBeAg seroclearance or presence of liver cirrhosis. The mathematical modelling from a long‐term follow‐up of chronic hepatitis B patients on entecavir shows that HBsAg clearance requires decades of treatment. Thus, lifelong therapy is inevitable in entecavir‐treated patients to achieve functional cure.