Phase 1b/2a randomized study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with chronic hepatitis B.

BACKGROUND AND AIM: The induction of effective CD8+ T cells is thought to play a critical role in the functional cure of chronic hepatitis B (CHB). Additionally, the use of checkpoint inhibitors is being evaluated to overcome T cell dysfunction during CHB. APPROACH AND RESULTS: A chimpanzee adenoviral vector (ChAdOx1-HBV) and a Modified vaccinia Ankara boost (MVA-HBV) encoding the inactivated polymerase, core, and S region from a consensus genotype C HBV were studied. The trial enrolled 55 patients with virally-suppressed CHB virus infection and HBsAg <4,000 IU/mL Group 1 received MVA-HBV intramuscularly (IM) on Day 0 and 28, Group 2 received ChAdOx1-HBV on Day 0/MVA-HBV on Day 28 (VTP-300), Group 3 received VTP-300 + low-dose nivolumab (LDN) on Day 28, and Group 4 received VTP-300 plus LDN with both injections. VTP-300 alone and in combination with LDN was well tolerated with no treatment-related serious adverse events. Reductions of HBsAg were demonstrated in the VTP-300 group 2: 3 of 18 patients with starting HBsAg < 50 IU/ml had durable log10 declines > 0.7 log10 2 months post last-dose. Group 3 (N=18) had reductions in HBsAg of 0.76 log10 and 0.80 log10 3 (p<0.001) at 2 and 7 months post last dose. Two developed persistent non-detectable HBsAg levels. CD4+ and CD8+ antigen-specific T cell responses were generated and there was a correlation between IFN-y ELISpot response and HBsAg decline in Group 2. CONCLUSIONS: VTP-300 induced CD4+ and CD8+ T cells and lowered HBsAg in a subset of patients with baseline values below 100 IU/ml. The addition of LDN resulted in significant reduction in surface antigen. VTP-300 is a promising immunotherapeutic to move forward alone or in combination therapies. IMPACT AND IMPLICATIONS: The induction of potent, durable CD8+ T cells may be critical to achieving a functional cure in chronic hepatitis B virus infection. A prime-boost immunotherapeutic consisting of an adenoviral-vector encoding hepatitis B antigens followed by a pox virus boost was shown to induce CD8+ T cells and to lower HBsAg in CHB patients, either alone or more impactfully when administered in conjunction with a checkpoint inhibitor. The use of immunotherapeutics CLINTRIALS: NCT047789.

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.

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.

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.

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.

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.

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).

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.

Evaluation of phosphorus adsorption capacity of sesame straw biochar on aqueous solution: influence of activation methods and pyrolysis temperatures.

The phosphorus (P) adsorption characteristic of sesame straw biochar prepared with different activation agents and pyrolysis temperatures was evaluated. Between 0.109 and 0.300 mg L(-1) in the form of inorganic phosphate was released from raw sesame straw biochar in the first 1 h. The release of phosphate was significantly enhanced from 62.6 to 168.2 mg g(-1) as the pyrolysis temperature increased. Therefore, sesame straw biochar cannot be used as an adsorbent for P removal without change in the physicochemical characteristics. To increase the P adsorption of biochar in aqueous solution, various activation agents and pyrolysis temperatures were applied. The amount of P adsorbed from aqueous solution by biochar activated using different activation agents appeared in the order ZnCl2 (9.675 mg g(-1)) > MgO (8.669 mg g(-1)) ⋙ 0.1N-HCl > 0.1N-H2SO4 > K2SO4 ≥ KOH ≥ 0.1N-H3PO4, showing ZnCl2 to be the optimum activation agent. Higher P was adsorbed by the biochar activated using ZnCl2 under different pyrolysis temperatures in the order 600 °C > 500 °C > 400 °C > 300 °C. Finally, the amount of adsorbed P by activated biochar at different ratios of biochar to ZnCl2 appeared in the order 1:3 ≒ 1:1 > 3:1. As a result, the optimum ratio of biochar to ZnCl2 and pyrolysis temperature were found to be 1:1 and 600 °C for P adsorption, respectively. The maximum P adsorption capacity by activated biochar using ZnCl2 (15,460 mg kg(-1)) was higher than that of typical biochar, as determined by the Langmuir adsorption isotherm. Therefore, the ZnCl2 activation of sesame straw biochar was suitable for the preparation of activated biochar for P adsorption.

Surgical treatment of solid pseudopapillary neoplasms of the pancreas and risk factors for malignancy.

BACKGROUND: The aim of this study was to identify clinical predictors of malignancy and surgical strategies for pancreatic solid pseudopapillary neoplasm (SPN) by analysis of surgical outcomes at a single institution. METHODS: All patients who underwent surgery for SPN between 1995 and 2010 were identified. Histopathology slides of all patients were reviewed by a specialized pathologist and the neoplasms were classified according to the criteria of the World Health Organization 2010. RESULTS: Of the 106 patients identified, 85 (80·2 per cent) were female, and the median age was 36 (range 10-65) years. Median tumour size was 4·5 (range 1·0-15·0) cm. Some 17 patients (16·0 per cent) were classified as having a high-grade malignant SPN. Tumour size of at least 5 cm was associated with high-grade malignant potential (P = 0·022). Although lymph nodes were removed from 40 patients (37·7 per cent), there were no nodal metastases. A total of five patients underwent en bloc resection of adjacent structures, including two with portal vein involvement. After a median follow-up of 56·9 months, two patients with high-grade malignant SPN had evidence of tumour recurrence in the lymph nodes and liver. CONCLUSION: SPN with a diameter of 5 cm or more is associated with a high-grade malignant phenotype. Complete surgical removal is associated with low recurrence rates.

Comparison of stent retriever and intra-arterial fibrinolysis in patients with acute ischaemic stroke.

BACKGROUND AND PURPOSE: Although the stent retriever (SR) has shown a better reperfusion rate and clinical outcome than the older generation mechanical clot retrieval device, it is uncertain whether the SR is superior to intra-arterial fibrinolysis (IAF). METHODS: Ischaemic stroke patients who were treated with SR or IAF as initial endovascular treatment modality for unilateral arterial occlusion in the anterior circulation were included. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction grade ≥2b. A favourable clinical outcome was defined as a modified Rankin Score ≤2 at 3 months. RESULTS: Between January 2009 and May 2012, 55 patients were treated with SR and 50 patients were treated with IAF. The baseline characteristics were similar between the two groups except for the occlusion site and rescue treatment. In binary logistic regression analysis adjusted for the occlusion site and rescue treatment, SR was independently associated with increased successful reperfusion [82.0% vs. 47.3%; odds ratio (OR) 5.21; 95% confidence interval (CI) 1.92-14.14) and a more favourable clinical outcome at 3 months (54.0% vs. 43.6%; OR 3.40; 95% CI 1.31-8.84). The frequency of symptomatic intracranial haemorrhage and mortality at 3 months was not different between the two groups. CONCLUSIONS: Stent retriever was as safe as and more effective than IAF. Our findings suggest that SR may be considered as an initial modality rather than IAF in acute stroke patients who undergo endovascular treatment.

The distribution of cerebral microbleeds determines their association with arterial stiffness in non-cardioembolic acute stroke patients.

BACKGROUND AND PURPOSE: Increased arterial stiffness causes vessel damage in the end-organs. Therefore small vessels in the brain may be susceptible to increased arterial stiffness. Cerebral microbleeds (CMBs) are topographically or pathophysiologically categorized as deep or infratentorial type and strictly lobar type. Whether the presence and location of CMBs are associated with brachial-ankle pulse wave velocity (baPWV) which represents a measure of arterial stiffness was investigated. METHODS: Between June 2006 and January 2012, 1137 consecutive patients diagnosed with non-cardioembolic acute ischaemic stroke and who underwent baPWV measurement and brain gradient-echo imaging were enrolled. CMBs were classified as deep or infratentorial or strictly lobar according to their location. Severity of leukoaraiosis was determined using the Fazekas scoring system. RESULTS: CMBs were found in 30.7% of the included patients. These patients were older than those without CMBs. Mean baPWV was higher in patients with CMBs than in those without (20 ± 5 m/s vs. 19 ± 5 m/s; P = 0.001). When comparing baPWV according to the location of the CMB, it was higher in the deep or infratentorial CMB group than in the strictly lobar CMB group (22 ± 5 m/s vs. 20 ± 5 m/s; P = 0.001). In univariate and multivariate multinomial logistic regression analyses, baPWV was found to be independently associated with deep or infratentorial CMBs. CONCLUSIONS: Arterial stiffness was independently associated with deep or infratentorial CMBs but not lobar CMBs. These findings suggest a pathophysiological association between arterial stiffness and CMBs in the deep or infratentorial region.

Viral load dynamics in adult patients with A(H1N1)pdm09 influenza.

SUMMARY The dynamics of influenza A viral load in respiratory samples collected from adult A(H1N1)pdm09 influenza patients were investigated. Three respiratory specimens were obtained every 2-4 days and clinical findings were recorded at the time each specimen was collected. A total of 105 serial specimens were collected from 35 patients. Viral clearance was more rapid in patients aged 15-29 years than patients aged 30-49 years (P < 0.01) or ≥ 50 years (P < 0.01). Hospitalized patients showed slow viral clearance compared to outpatients (P < 0.01). Resolution of cough and headache was correlated with viral load reduction in respiratory specimens. Viral shedding was found in 17 patients (48.6%) 5 days after symptom onset. Time to hospital visit after symptom onset was significantly correlated with prolonged viral shedding (odds ratio 9.0, 95% confidence interval 1.56-51.87, P = 0.01). These findings will contribute to infection control aspects with respect to managing patients with influenza virus infections.

High temperature stable PbS quantum dots.

For the fabrication of nanoparticle containing optical fibers by melt and draw technique, nanoparticle stability at high temperatures is a requirement. We report the synthesis of quantum dots at temperatures as high as 1000 °C, compatible with fiber drawing, stabilized for the first time by a prior low temperature heating step. It is observed that quantum dots formed by this two step heating leads to a better emission stability at high powers associated with a reversible phenomenon, making these nanomaterials suitable for further technological applications.

The association between asymptomatic coronary artery disease and CHADS2 and CHA2 DS2 -VASc scores in patients with stroke.

BACKGROUND AND PURPOSE: CHADS2 and CHA2 DS2 -VASc scores are measurement tools that stratify thromboembolic risk in patients with non-valvular atrial fibrillation, and are predictive of cerebral atherosclerosis, fatal stroke and ischaemic heart disease. Patients with higher CHADS2 and CHA2 DS2 -VASc scores are more likely to have had an akinetic/hypokinetic left ventricular segment or a recent myocardial infarction, all of which are associated with coronary artery disease (CAD). Most of the CHADS2 score components are also risk factors for atherosclerosis. Thus, CHADS2 and CHA2 DS2 -VASc scores may be predictive of CAD. METHODS: In all, 1733 consecutive patients with acute ischaemic stroke who underwent multi-slice computed tomography coronary angiography were enrolled. The association of CHADS2 and CHA2 DS2 -VASc scores with the presence and severity of CAD was investigated. RESULTS: Of the 1733 patients, 1220 patients (70.4%) had any degree of CAD and 576 (33.3%) had significant CAD (≥ 50% stenosis in at least one coronary artery). As the CHADS2 and CHA2 DS2 -VASc scores increased, the presence of CAD also increased (P < 0.001). The severity of CAD was correlated with CHADS2 score (Spearman coefficient 0.229, P < 0.001) and CHA2 DS2 -VASc score (Spearman coefficient 0.261, P < 0.001). In multivariate analysis, after adjusting for confounding factors, CHADS2 and CHA2 DS2 -VASc scores ≥2 were independently associated with CAD. The CHA2 DS2 -VASc score was a better predictor of the presence of CAD than the CHADS2 score on area under the curve analysis. CONCLUSION: CHADS2 and CHA2 DS2 -VASc scores were predictive of the presence and severity of CAD in patients with stroke. When a patient has high CHADS2 or CHA2 DS2 -VASc scores, physicians should consider coronary artery evaluation.

The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are extravasations of blood from lipohyalinized or amyloid angiopathic cerebral arterioles, and the presence and numbers of CMBs are significantly associated with the development of oral anticoagulation (OA)-related intracranial haemorrhage (ICH). The aim of this study was to investigate whether there is a difference in CMBs burden according to CHADS(2) scores or CHA(2) DS(2) -VASc scores in non-valvular atrial fibrillation (NVAF) patients. METHODS: We included 550 ischaemic stroke patients who had NVAF and who had undergone brain magnetic resonance imaging (MRI) with gradient-recalled echo (GRE) T2 sequences from our prospective stroke registry between January 2005 and November 2011. We calculated CHADS(2) scores and CHA(2) DS(2) -VASc scores for all patients based on their underlying cardiovascular diseases. The presence, location and number of CMBs were assessed in each patient. We also investigated whether the CMBs were actually associated with the development of ICH during follow-up. RESULTS: The mean patient age was 70.4 ± 10.5 years, and 324 (58.9%) patients were men. One-hundred and seventy-three patients (31.5%) had CMBs detected on GRE MRI. Higher CHADS(2) scores or CHA(2) DS(2) -VASc scores were strongly associated with the presence and number of CMBs. During follow-up of median 3.1 ± 1.6 years, the presence of CMBs was independently associated with the development of ICH, whilst the CHADS(2) scores or CHA(2) DS(2) -VASc scores were not. CONCLUSIONS: Considering the positive association between the presence of CMBs and OA-related ICH, our results suggest that the increase in ICH in high-risk groups during OA may be related to an increased burden of CMBs.

Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds.

For the last several decades, antimicrobial compounds have been used to promote piglet growth at weaning through the prevention of subclinical and clinical disease. There are, however, increasing concerns in relation to the development of antibiotic-resistant bacterial strains and the potential of these and associated resistance genes to impact on human health. As a consequence, European Union (EU) banned the use of antibiotics as growth promoters in swine and livestock production on 1 January 2006. Furthermore, minerals such as zinc (Zn) and copper (Cu) are not feasible alternatives/replacements to antibiotics because their excretion is a possible threat to the environment. Consequently, there is a need to develop feeding programs to serve as a means for controlling problems associated with the weaning transition without using antimicrobial compounds. This review, therefore, is focused on some of nutritional strategies that are known to improve structure and function of gastrointestinal tract and (or) promote post-weaning growth with special emphasis on probiotics, prebiotics, organic acids, trace minerals and dietary protein source and level.

Surgical strategies for non-functioning pancreatic neuroendocrine tumours.

BACKGROUND: The purpose of this study was to identify management strategies for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) by analysis of surgical outcomes at a single institution. METHODS: Archived records of patients with NF-PNETs who underwent surgery between 1994 and 2010 were reviewed. RESULTS: Among 125 patients, the median tumour size was 2·5 (range 0·15-20·5) cm. Of the 51 NF-PNETs with a diameter of no more than 2 cm, 12 (24 per cent) were diagnosed as carcinoma. Overall 20 patients (16·0 per cent) had metastases to the lymph nodes. The minimum size of the tumour with lymph node metastasis was 1·2 cm. Having a NF-PNET of 2 cm or larger significantly increased the probability of a poorly differentiated carcinoma (P = 0·006), and having a NF-PNET of at least 2·5 cm significantly increased the probability of lymph node metastasis (P = 0·048). The 5-year cumulative survival rate after curative resection was 89·7 per cent. During a median follow-up of 31·5 months, there were 27 recurrences (23·1 per cent) and 13 disease-specific deaths (11·1 per cent) among the 117 patients who had an R0 resection. All patients who underwent repeat operations were alive without additional recurrence after a mean(s.d.) follow-up of 27·1(18·0) months. CONCLUSION: Curative surgery should be performed for control of primary NF-PNETs. Lymph node dissection for NF-PNETs of 2·5 cm or larger and at least node sampling for tumours with a diameter of 1 cm or more are recommended. Debulking surgery should be considered for advanced tumours.