Association between aortic calcification and stable obstructive coronary artery disease

Aims

Atrial fibrillation and flutter remain an important cause of morbidity in adults with atrial septal defect (ASD). This study aimed at investigating predictors for late (≥ 1 month after repair) atrial arrhythmia.

Methods

Patients who underwent ASD closure after the age of 18 years, were selected through the databases of three medical centres in Belgium. Preprocedural, periprocedural and follow-up data were extracted. Univariate and multivariate Cox-regression analysis was performed. Kaplan-Meier analysis was performed for any independent predictor of late atrial arrhythmia.

Results

A total of 155 patients (38 men and 117 women) was included. Twenty-four patients (median age 48.3 years, range 19.9-79.8) underwent surgical and 131 (median age 57.6 years, range 18.2-86.9) underwent transcatheter closure. Thirty-nine patients (25.2%) presented with late atrial arrhythmia. Male gender (P = 0.008), creatinine (P = 0.002), atrial arrhythmia before (P < 0.0001) and within 1 month after repair (P = 0.001) and a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg (P < 0.0001) correlated with late atrial arrhythmia in univariate Cox-regression analysis. Multivariate analysis showed that mPAP ≥ 25 mm Hg (HR 3.72; 95%CI 1.82-7.59; P < 0.0001) and the presence of atrial arrhythmia before (HR 3.22; 95%CI 1.56-6.66; P = 0.002) and within 1 month after repair (HR 2.08; 95%CI 2.08-15.92; P = 0.001) were predictive of late atrial arrhythmia. Kaplan-Meier analysis showed that patients with a mPAP ≥ 25 mm Hg had a higher risk at developing late atrial arrhythmia (P < 0.0001).

Conclusion

In patients with ASD type secundum, a mPAP ≥ 25 mm Hg is an independent predictor of late atrial arrhythmia. The presence of pulmonary hypertension before repair should raise awareness for atrial arrhythmias and may be used to guide therapy.     

Formation of unconventional standing waves at graphene edges by valley mixing and pseudospin rotation

We investigate the roles of the pseudospin and the valley degeneracy in electron scattering at graphene edges. It is found that they are strongly correlated with charge density modulations of short-wavelength oscillations and slowly decaying beat patterns in the electronic density profile. Theoretical analyses using nearest-neighbor tight-binding methods and first-principles density-functional theory calculations agree well with our experimental data from scanning tunneling microscopy. The armchair edge shows almost perfect intervalley scattering with pseudospin invariance regardless of the presence of the hydrogen atom at the edge, whereas the zigzag edge only allows for intravalley scattering with the change in the pseudospin orientation. The effect of structural defects at the graphene edges is also discussed.     

Structural and functional analysis of an essential nucleoporin heterotrimer on the cytoplasmic face of the nuclear pore complex

So far, only a few of the interactions between the ≈30 nucleoporins comprising the modular structure of the nuclear pore complex have been defined at atomic resolution. Here we report the crystal structure, at 2.6 Å resolution, of a heterotrimeric complex, composed of fragments of three cytoplasmically oriented nucleoporins of yeast: Nup82, Nup116, and Nup159. Our data show that the Nup82 fragment, representing more than the N-terminal half of the molecule, folds into an extensively decorated, seven-bladed β-propeller that forms the centerpiece of this heterotrimeric complex and anchors both a C-terminal fragment of Nup116 and the C-terminal tail of Nup159. Binding between Nup116 and Nup82 is mutually reinforced via two loops, one emanating from the Nup82 β-propeller and the other one from the β-sandwich fold of Nup116, each contacting binding pockets in their counterparts. The Nup82-Nup159 interaction occurs through an amphipathic α-helix of Nup159, which is cradled in a large hydrophobic groove that is generated from several large surface decorations of the Nup82 β-propeller. Although Nup159 and Nup116 fragments bind to the Nup82 β-propeller in close vicinity, there are no direct contacts between them, consistent with the noncooperative binding that was detected biochemically. Extensive mutagenesis delineated hot-spot residues for these interactions. We also showed that the Nup82 β-propeller binds to other yeast Nup116 family members, Nup145N, Nup100 and to the mammalian homolog, Nup98. Notably, each of the three nucleoporins contains additional nuclear pore complex binding sites, distinct from those that were defined here in the heterotrimeric Nup82•Nup159•Nup116 complex.     

Successful neoadjuvant treatment with radiochemotherapy and systemic chemotherapy for the locally advanced pancreatic head cancer: report of a case

A 49-year-old man was admitted to the hospital for the upper abdominal pain and was diagnosed as unresectable pancreatic head cancer because of the invasion around the superior mesenteric artery. He was treated with radiochemotherapy, followed by systemic gemcitabine alone for 3 courses. He was further treated with systemic gemcitabine plus S?1 combination therapy for 5 courses. CT examination after these treatments showed a dramatic reduction of the tumor at the head of the pancreas and a pancreatoduodenectomy was performed. Pathologically, there was no residual malignant tumor. He has had no recurrent tumor up until now. Several studies of gemcitabine plus S-1 combination therapy show higher response rates for unresectable tumors. The current case indicates the effectiveness of the radiochemotherapy and gemcitabine plus S?1 combination therapy for locally advanced pancreatic head cancer as a neoadjuvant setting. We consider that multidisciplinary treatment including gemcitabine plus S?1 therapy may prolong the survival time by curative operation.     

The prognostic factors of pancreatic cancer can be different according to clinical stages]

BACKGROUND/AIMS: The prognosis of patients with pancreatic cancer remains very poor. Although many studies have evaluated the prognostic factors of pancreatic cancer, their results are inconclusive because of different inclusion criteria, tumor stages, and treatment modalities. This large scale retrospective analysis was performed to assess whether active treatment of pancreatic cancer, even in its advanced stage, could improve patients' survival. In addition, we sought to identify factors associated with favorable prognosis of pancreatic cancer. METHODS: Between 1994 and 2004, a total of 971 patients with pancreatic cancer were treated at Asan Medical Center. The patients were classified into three groups according to clinical stages: resectable (RE, n=226), locally advanced (LA, n=409), and far advanced (FA, n=336). Treatment response and prognostic factors for survival were analyzed in each group. RESULTS: Compared to supportive care, active treatment significantly increased the median survival time in all groups (RE: 18.0 vs. 9.0 months; LA: 10.0 vs. 7.0 months; FA: 5.0 vs. 3.0 months). Multivariate analysis showed that prognostic factors for survival differed according to clinical stages. In the RE group, unfavorable prognostic factors were high CA 19-9, poor histologic differentiation, large tumor size, and regional lymph node involvement. In the FA group, however, poor outcomes were associated with old age, poor performance status, and hypoalbuminemia. CONCLUSIONS: More active treatment of pancreatic cancer, even in advanced stage, can make a significant difference in terms of patient's survival. The prognosis of resectable pancreatic cancer is dependent on tumor-related factors, while the prognosis of patients with far advanced pancreatic cancer is dependent on patient-related factors.     

Virologic and biochemical responses to clevudine in patients with chronic HBV infection‐ associated cirrhosis: data at week 48

Summary. Clevudine shows high rates of virologic and biochemical responses in patients with chronic hepatitis B. However, the efficacy and safety of clevudine in patients with cirrhosis are unknown. The aims of this study were to evaluate the safety and to assess the virologic and the biochemical responses to clevudine in patients with cirrhosis with chronic hepatitis B virus (HBV) infection. We reviewed data from treatment‐naïve patients with chronic hepatitis B with and without cirrhosis who started clevudine between April 2007 and March 2008 (n = 52, hepatitis B without cirrhosis n = 21 and chronic hepatitis B with cirrhosis n = 31) at Korea University Ansan/Guro Hospital. All of the patients were treated for more than 48 weeks. The mean age was older in the patients with cirrhosis. Baseline HBV DNA levels were 6.9 and 7.78 log copies/mL (P = 0.042), and alanine aminotransferase (ALT) levels were 104.9 and 147.4 IU/L (P = 0.204), for those with and without cirrhosis, respectively. Virologic response (HBV DNA <1000 copies/mL) (87.1%vs 71.4%, P = 0.24) and biochemical response (83.9%vs 80.9%, P = 0.99) at week 48 were not significantly different between the two groups. Early virologic response at week 12 was even higher in the patients with cirrhosis (61.3%vs 28.6%, P = 0.026). Neither ALT flare nor newly onset hepatic decompensation was found in the patients with cirrhosis, whereas ALT flare was transiently observed in 14.3% of the chronic hepatitis group. In conclusion, although clevudine may produce a transient elevation of ALT during the early treatment period, such findings were not observed in patients with cirrhosis and the virologic and biochemical responses of the groups were comparable.     

Radiotherapy for 65 patients with advanced unresectable hepatocellular carcinoma

AIM： To evaluate the efficacy of radiotherapy （RT） in patients with advanced unresectable hepatocellular carcinoma （HCC）. METHODS： A total of 65 patients were treated with RT in the Korea University Medical Center. The median age of the patients was 60 years, and 86.2% were men. 18.5% and 81.5% of the patients were diagnosed as TNM stage Ⅲ and Ⅳ-A, respectively. Treatment response was assessed 4 mo after initiation of RT. Tumor regression rate 1 mo after initiation of RT （TRR1m） was also assessed. Duration of survival was calculated from the initiation of RT. RESULTS： The objective treatment response was 56.9%. The 12 mo survival rate was 34.7%. Predictive factors for survival were Child-Pugh grade, α-fetoprotein level and treatment response. An objective response was achieved more frequently in patients with TRR1m ≥ 20% than in those with TRR1m 〈 20% （P 〈 0.001）. CONCLUSION： RT is effective in treating advanced HCC with a tumor response rate of 56.9%.     

PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes

Background and Aims: In a previous study, the authors found that reduced expression of peroxisome proliferator‐activated receptor (PPAR)‐α might play an important role in developing nonalcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the effects of PPAR‐α and ‐γ agonists on NAFLD and verify the mechanisms underlying the PPAR‐α and ‐γ agonist‐induced improvements by evaluating the hepatic gene expression profile involved in fatty‐acid metabolism, using the Otsuka–Long Evans–Tokushima fatty (OLETF) rat. Methods: Rats were assigned to a control group (group I), fatty liver group (group II), PPAR‐α agonist treatment group (group III), or PPAR‐γ agonist treatment group (group IV). Fasting blood glucose, total cholesterol, and triglycerides were measured. Liver tissues from each group were processed for histological and gene expression analysis. mRNAs of enzymes involved in fatty‐acid metabolism and tumor necrosis factor (TNF)‐α were measured. Results: After 28 weeks treatment with PPAR‐α or ‐γ agonist, steatosis of the liver was improved in groups III and IV compared with group II. Fasting blood glucose levels were significantly lower in groups III and IV than in group II. In group III, mRNA expression of fatty‐acid β‐oxidation enzymes, such as fatty‐acid transport protein (FATP), fatty‐acid binding protein, carnitine palmitoyltransferase II, medium‐chain acyl‐CoA dehydrogenase (MCAD), long‐chain acyl‐CoA dehydrogenase, and acyl‐CoA oxidase, was significantly increased. However, the treatment‐induced modulation of fatty‐acid β‐oxidation enzymes was confined to FATP and MCAD in group IV. TNF‐α tended to be reduced in groups III and IV compared with group II. Conclusions: Treatment with PPAR agonists, especially a PPAR‐α agonist, improved the histological and biochemical parameters in the OLETF rat model by inducing fatty‐acid metabolic enzymes.     

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.