Effect of total cholesterol level variabilities on cerebrovascular disease.

OBJECTIVE: Hyperlipidemia is a risk factor of cerebrovascular disease (CVD). However, the relationship between CVD and cholesterol variability is less clear. This study assesses the relationship between cholesterol change and CVD risk. PATIENTS AND METHODS: We reviewed 480,830 people from 20 to 99 years with 2 health check-ups from 2002 to 2015 from the Korean National Health Insurance (KNHI) database. People's baseline and follow-up cholesterol levels were classified into low (<180 mg/dL), moderate (≥180 mg/dL and <240 mg/dL), and high (≥240 mg/dL). Participants were divided into 9 groups (low-to-low, low-to-moderate, low-to-high, moderate-to-low, moderate-to-moderate, moderate-to-high, high-to-low, high-to-moderate, high-to-high). RESULTS: Low to high cholesterol level is associated with hemorrhagic stroke (aHR1 = 1.59; 95% CI 1.12-2.28 and aHR2 = 1.56; 95% CI 1.07-2.25). Low to moderate/high cholesterol level is associated with ischemic stroke and occlusion/stenosis (for low to moderate, aHR1 = 1.11; 95% CI 1.04-1.17 and aHR2 = 1.14; 95% CI 1.07-1.21 for ischemic stroke and aHR1 = 1.18; 95% CI 1.07-1.29 and aHR2 = 1.20; 95% CI 1.08-1.32 for occlusion/stenosis, for low to high, aHR1 = 1.42; 95% CI 1.20-1.67 and aHR2 = 1.28; 95% CI 1.08-1.52 for ischemic stroke and aHR1 = 1.86; 95% CI 1.46-2.36 and aHR2= 1.74; 95% CI 1.36-2.23 for occlusion/stenosis). Moderate to high cholesterol level is associated with ischemic stroke and occlusion/stenosis (for ischemic stroke, aHR1 = 1.12; 95% CI 1.05-1.20 and aHR2 = 1.10; 95% CI 1.03-1.17, for occlusion/stenosis, aHR1 = 1.21; 95% CI 1.10-1.33 and aHR2 = 1.19; 95% CI 1.08-1.32). Moderate to low cholesterol level is associated with ischemic and hemorrhagic stroke and occlusion/stenosis (for ischemic, aHR1 = 1.15; 95% CI 1.09-1.21, for hemorrhagic, aHR1 = 1.14; 95% CI 1.01-1.28, for occlusion/stenosis, aHR1 = 1.14; 95% CI 1.05-1.23). High to low cholesterol level is associated with ischemic stroke and occlusion/stenosis (for ischemic stroke, aHR1 = 1.51; 95% CI 1.33-1.71 and aHR2 = 1.20; 95% CI 1.05-1.36, for occlusion/stenosis, aHR1 = 1.50; 95% CI 1.24-1.81). CONCLUSIONS: Our study shows that cholesterol changes, especially larger changes, lead to an increase in CVD, which demonstrates that cholesterol variability may increase CVD.

Hyperattenuating lesions after mechanical thrombectomy in acute ischaemic stroke: factors predicting symptomatic haemorrhage and clinical outcomes.

AIM: To evaluate the clinical significance of hyperattenuating lesions on CT after mechanical thrombectomy for acute ischaemic stroke, and to identify imaging factors that predict symptomatic haemorrhage and unfavourable outcomes. MATERIALS AND METHODS: Seventy-eight patients with acute ischaemic stroke in the anterior circulation who underwent mechanical thrombectomy were evaluated. All patients underwent post-interventional unenhanced computed tomography (CT) within 24 h and follow-up CT or magnetic resonance imaging (MRI) within 7 days. Baseline characteristics and clinical outcomes were compared between patients with and without hyperattenuating lesions. In patients with hyperattenuating lesions, clinical and imaging factors that predict symptomatic haemorrhage and unfavourable outcomes were determined. RESULTS: Fifty-six of 78 patients (71.8%) demonstrated hyperattenuating lesions on post-interventional CT. Patients with hyperattenuating lesions showed lower Alberta Stroke Program Early CT score (ASPECTS), persistent/symptomatic haemorrhage, and unfavourable outcomes than those without. In patients with hyperattenuating lesions, larger hyperattenuating lesion volume (>21.3 ml; OR, 55.60, p<0.001) and perilesional oedema (OR, 46.04, p=0.015) were independent factors predicting symptomatic haemorrhage. Older age (OR, 1.2, p=0.006) and lower ASPECTS (OR, 0.45, p=0.046) were independent factors predicting unfavourable outcomes in patients with hyperattenuating lesions. Adding the volume of the hyperattenuating lesion to age and ASPECTS increased the predictive performance of unfavourable outcomes (area under the curve 0.874 versus 0.934, p=0.043). CONCLUSIONS: Hyperattenuating lesions on post-interventional CT are associated with increased risk of symptomatic haemorrhage and unfavourable outcomes. Larger hyperattenuating lesion volume is an independent factor of symptomatic haemorrhage and it has added predictive value for unfavourable outcomes.

Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice.

Excessive body fat and the related dysmetabolic diseases affect both developed and developing countries. The aim of this study was to investigate the beneficial role of a bacterial culture supernatant (hereafter: BS) of Lactobacillus and Bifidobacterium and their potential mechanisms of action on white-fat browning and lipolysis. For selection of four candidates among 55 Lactic acid producing bacteria (LAB) from human infant faeces, we evaluated by Oil Red O staining and Ucp1 mRNA quantitation in 3T3-L1 preadipocytes. The expression of browning and lipolysis markers was examined along with in vitro assays. The possible mechanism was revealed by molecular and biological experiments including inhibitor and small interfering RNA (siRNA) assays. In a mouse model, physiological, histological, and biochemical parameters and expression of some thermogenesis-related genes were compared among six experimental groups fed a high-fat diet and one normal-diet control group. The results allow us to speculate that BS treatment promotes browning and lipolysis both in vitro and in vivo. Moreover, the BS may activate thermogenic programs via a mechanism involving PKA-CREB signaling in 3T3-L1 cells. According to our data, we can propose that two LAB strains, Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508, may be good candidates for a dietary supplement against obesity and metabolic diseases; however, further research is required for the development as dietary supplements or drugs.

Association between body mass index and stroke severity in acute ischaemic stroke with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log-linear regression with a Poisson distribution and binary logistic regression analysis. RESULTS: A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores [median 5, interquartile range (IQR) 2-14] of normal-weight patients, the NIHSS scores (median 9, IQR 4-19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1-12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09-2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal-weight patients. CONCLUSION: An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short-term outcomes in patients with NVAF.

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Synthesis and characterization of iodovanadinite using PdI2, an iodine source for the immobilisation of radioiodine.

The synthesis of a palladium-containing iodovanadinite derivative, hypothetically "PdPb9(VO4)6I2", was attempted using PdI2 as a source of iodine in searching for a novel waste form for radioiodine. Stoichiometric amounts of Pb3(VO4)2 and PdI2 were batched and reacted at elevated temperatures in sealed vessels. Batched material was also subjected to high-energy ball-milling (HEBM) in order to reduce reaction time and the potential for iodine volatilization during subsequent reaction at 200-500 °C. The resulting products were characterized using X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray analysis, IR spectroscopy, thermal analysis and Pd K XANES. Results showed that PdI2 can function as a sacrificial iodine source for the formation of iodovanadinite, prototypically Pb10(VO4)6I2, however, the incorporation of Pd into this phase was not definitively observed. The sacrificial reaction mechanism involved the decomposition of PdI2 to Pd metal and nascent I2, with the latter incorporated into the iodovanadinite Pb10(VO4)6I2 phase. In comparison to processing using standard solid state reaction techniques, the use of HEBM prior to high temperature reaction generates a more homogeneous end-product with better iodine retention for this system. Overall, the key novelty and importance of this work is in demonstrating a method for direct immobilisation of undissolved PdI2 from nuclear fuel reprocessing, in a composite wasteform in which I-129 is immobilised within a durable iodovandinite ceramic, encapsulating Pd metal.

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.

Rational Design of Low Cost and High Energy Lithium Batteries through Tailored Fluorine-free Electrolyte and Nanostructured S/C Composite.

We report a new Li-S cell concept based on an optimized F-free catholyte solution and a high loading nanostructured C/S composite cathode. The Li2 S8 present in the electrolyte ensures both buffering against active material dissolution and Li+ conduction. The high S loading is obtained by confining elemental S (≈80 %) in the pores of a highly ordered mesopores carbon (CMK3). With this concept we demonstrate stabilization of a high energy density and excellent cycling performance over 500 cycles. This Li-S cell has a specific capacity that reaches over 1000 mA h g-1 , with an overall S loading of 3.6 mg cm-2 and low electrolyte volume (i.e., 10 µL cm-2 ), resulting in a practical energy density of 365 Wh kg-1 . The Li-S system proposed thus meets the requirements for large scale energy storage systems and is expected to be environmentally friendly and have lower cost compared with the commercial Li-ion battery thanks to the removal of both Co and F from the overall formulation.

RAB7A phosphorylation by TBK1 promotes mitophagy via the PINK-PARKIN pathway.

Removal of damaged mitochondria is orchestrated by a pathway involving the PINK1 kinase and the PARKIN ubiquitin ligase. Ubiquitin chains assembled by PARKIN on the mitochondrial outer membrane recruit autophagy cargo receptors in complexes with TBK1 protein kinase. While TBK1 is known to phosphorylate cargo receptors to promote ubiquitin binding, it is unknown whether TBK1 phosphorylates other proteins to promote mitophagy. Using global quantitative proteomics, we identified S72 in RAB7A, a RAB previously linked with mitophagy, as a dynamic target of TBK1 upon mitochondrial depolarization. TBK1 directly phosphorylates RAB7AS72, but not several other RABs known to be phosphorylated on the homologous residue by LRRK2, in vitro, and this modification requires PARKIN activity in vivo. Interaction proteomics using nonphosphorylatable and phosphomimetic RAB7A mutants revealed loss of association of RAB7AS72E with RAB GDP dissociation inhibitor and increased association with the DENN domain-containing heterodimer FLCN-FNIP1. FLCN-FNIP1 is recruited to damaged mitochondria, and this process is inhibited in cells expressing RAB7AS72A. Moreover, nonphosphorylatable RAB7A failed to support efficient mitophagy, as well as recruitment of ATG9A-positive vesicles to damaged mitochondria. These data reveal a novel function for TBK1 in mitophagy, which parallels that of LRRK2-mediated phosphorylation of the homologous site in distinct RABs to control membrane trafficking.

Concurrent hyperthermia and re-irradiation for recurrent high-grade gliomas.

Salvage therapy for recurrent high grade gliomas (HGG) includes surgery, radiotherapy and chemotherapy, however, standard treatment does not exist. We evaluated the tolerability and efficacy of re-irradiation (re-RT) with hyperthermia (HT) for patients with recurrent HGG. From September 2010 to July 2015, 20 patients with recurrent HGG were treated with re-RT and HT. The radiotherapy dose of 30 Gray (Gy) was delivered with 2 Gy per fraction daily, and HT was performed twice weekly. Primary endpoints were treatment compliance and toxicity. Second endpoints were overall survival (OS) and progression free survival (PFS). The median interval between initial RT and re-RT was 11 months. During re-RT with HT, there were no significant acute morbidities over grade 3. Median overall survival (OS) from re-irradiation was 8.4 months and the 6 and 12 months survival rate were 67% and 30%, respectively. The median progression free survival (PFS) from re-irradiation was 4.1 month. Our findings suggested that concurrent re-RT with HT was a safe and well-tolerated. In addition, the combination re-RT and HT could be a valuable salvage treatment option for selected recurrent HGG patients with poor performance status.

Evaluation of sulphur amino acid requirement of male Korean native ducklings from hatch to 21 day of age.

1. A dose-response experiment was conducted with male Korean native ducklings (KND) to evaluate the total sulphur amino acid (TSAA) requirement from hatch to 21 d of age. 2. A completely randomised design with 7 dietary TSAA concentrations (0.62%, 0.65%, 0.68%, 0.71%, 0.74%, 0.77% and 0.80%) were used with 6 replications per treatment. 3. Body weight (BW) and feed intake were measured weekly to calculate average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR). One duckling per pen (n = 6) was killed by cervical dislocation to weigh empty body and drumsticks at the conclusion of experiment. 4. BW was improved significantly with increasing TSAA content, in a non-linear manner. A significant decrease of FCR was shown with increasing TSAA contents. TSAA requirement was determined by taking a mean value after fitting the data to both a linear-plateau and a quadratic-plateau model. Estimated TSAA requirements were 0.70%, 0.70%, 0.66% and 0.70% for the maximum BW, ADG and ADFI and for the minimum FCR, respectively. Increasing TSAA content improved quantity of full body weight (FBW), empty body weight (EBW) and drumstick weight (DSW), but there was no effect on proportion of DSW in relation to EBW and proportion of EBW to FBW. 5. In conclusion, the growth of male KND during 1 to 21 d of age was improved with increasing TSAA content, suggesting optimal TSAA requirements estimated by two analysis models.

Intrahepatic Artery Pseudoaneurysm-induced Hemobilia Caused by a Plastic Biliary Stent After ABO-incompatible Living-donor Liver Transplantation: A Case Report.

Bile leakage after duct-to-duct anastomosis in living-donor liver transplantation (LDLT) can mostly be managed by therapeutic endoscopic retrograde cholangiopancreatography. Following this, various complications such as biliary infection, pancreatitis, perforation, and bleeding can occur, and endoscopic sphincterotomy is primarily associated with post- endoscopic retrograde cholangiopancreatography bleeding; other causes have been published in case reports. In the present case, a plastic biliary stent used for treating liver abscesses and leakage at the bile duct anastomosis site after ABO-incompatible LDLT resulted in an intrahepatic artery pseudoaneurysm and hemobilia, which were managed by angiography and coil embolization. Although the complex postoperative course after LDLT can obscure the prompt diagnosis of an intrahepatic artery pseudoaneurysm and hemobilia, biliary stenting should be considered as a possible cause.

Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder.

Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

BACKGROUND: There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. METHODS: Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. RESULTS: A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF. CONCLUSION: External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).

Prognostic significance of volume-based 18F-FDG PET/CT parameter in patients with surgically resected non-small cell lung cancer. Comparison with immunohistochemical biomarkers.

AIM: We investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) parameters compared with other factors including several immunohistochemical biomarkers in patients with surgically resected non-small cell lung cancer (NSCLC). STUDY PARTICIPANTS: 290 patients with surgically resected and histopathologically confirmed NSCLC. The maxmum standardized uptake value (SUVmax) and metabolic tumour volume (MTV) of the primary tumour were obtained on 18F-FDG PET/ computed tomography (CT) for initial staging and Ki-67 labeling index (LI), p16, CD31 and cyclin E were evaluated in the primary tumours by immunohistochemical staining. Survival analyses for variables including PET parameters, immunohistochemical biomarker and other clinical factors were performed using the Kaplan-Meier method and Cox proportional hazards regression analysis. RESULTS: In univariate analyses, tumour stage, tumour size, and MTV were significant prognostic factors for decreased overall survival (OS) and disease-free survival (DFS). Multivariate analyses showed MTV and tumour stage were significant predictors of poor OS (MTV, hazard ratio (HR) = 1.135, p = 0.015; stage, HR = 0.644, p = 0.025) and DFS (MTV, HR = 1.128, p = 0.043; stage, HR = 0.541, p = 0.009). CONCLUSION: The MTV of primary tumours is a significant prognostic factor for survival along with tumour stage in patients with surgically resected NSCLC. The MTV can predict OS and DFS better than immunohistochemical biomarkers.

A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

The apparent metabolizable energy requirement of male Korean native ducklings from hatch to 21 days of age.

A study was conducted to determine the apparent metabolizable energy (AME) requirement of Korean native ducklings for hatch to 21 d of age. A total of 336 one-day-old male Korean native ducklings were used in a completely randomized design having 8 dietary treatments to provide a range of AME content from 2,600 to 3,300 kcal/kg (i.e., 100 kcal/kg disparity). Eight experimental diets containing varying levels of AME were formulated to meet the NRC (1994) nutrient specifications. Ducklings were randomly allocated to 48 pens (6 replicates per treatment and 7 ducklings per pen) and were offered their respective diets on an ad libitum basis for the period of study. Body weight and feed intake were measured weekly to calculate feed conversion ratio, energy intake, and protein intake. Two ducklings per pen (n = 6) were euthanized via cervical dislocation to weigh empty body and drumsticks at the conclusion of the experiment. Data were fitted to both linear-plateau and quadratic-plateau models for estimation of the AME requirements for Korean native ducklings for hatch to 21 d of age. The estimated AME requirements were 2,953, 3,007, and 2,950 kcal AME/kg diet for maximum daily gain, daily feed intake, and for minimum feed conversion ratio, respectively.

Net energy content of dry extruded-expelled soybean meal fed with or without enzyme supplementation to growing pigs as determined by indirect calorimetry.

Two experiments were conducted to determine the NE content of dry extruded-expelled soybean (DESBM) and the effect of a multienzyme carbohydrase (MC) mixture on the NE content of DESBM and to determine the effect of diet design on NE values in growing pigs using indirect calorimetry (IC). In Exp. 1, 24 barrows (19.6 ± 0.51 kg BW) were allotted in a completely randomized design to 4 dietary treatments: a corn­soybean meal basal diet (Diet A), a diet containing Diet A and DESBM in an 80:20 ratio with a constant CP (Diet B), a diet with an 80:20 ratio of Diet A and DESBM with a constant corn:soybean meal ratio (Diet C), and a diet with simple substitution of Diet A with DESBM in an 80:20 ratio (Diet D). Pigs were fed in metabolism crates for a period of 16 d to determine the DE and ME and thereafter were moved into an indirect calorimeter where O2 consumption and CO2 production were measured to determine heat production and fasting heat production. The NE content of DESBM was calculated (difference method) to be 2,632, 2,548 and 2,540 kcal/kg DM in diets B, C, and D, respectively. Respective values obtained with published prediction equations were 2,624, 2,530 and 2,436 kcal/kg. In Exp. 2, 24 barrows (16.9 ± 0.76 kg BW) were randomly allotted to 1 of 4 treatments. The diets were a corn­soybean meal basal diet and a diet containing the basal diet and DESBM in an 80:20 ratio with a constant corn:soybean meal ratio with or without 2 levels (0.05% and 0.1%) of MC. The experimental procedures were similar to those described in Exp. 1. Enzyme supplementation improved (P < 0.0001) the DE, ME, and NE content of the DESBM. Multienzyme carbohydrase at 0.05% and 0.1% of the diet improved NE values of DESBM by 4.9% and 3.7%, respectively. In conclusion, the NE values of DESBM obtained with the IC method were higher than the values obtained with prediction equations; the disparity was least when diets were formulated with a constant CP level. However, as the difference method was used to determine the NE of ingredient, it is more appropriate to maintain a constant ratio between the ingredients. Also, the NE value of DESBM obtained for diets C and D were not different. Hence, the average NE value of DESBM evaluated was 2,544 kcal/kg DM. Enzyme supplementation improved the NE content of DESBM fed to growing pigs.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.