This manuscript represents an appraisal of the evidence in support of
l
-ornithine-
l
-aspartate (LOLA) for the management and treatment of hepatic encephalopathy (HE) in cirrhosis. Meta-analyses of ...randomized controlled trials (RCTs) conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations. This included improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics. Emerging evidence from single RCTs show efficacy of LOLA for the treatment of post-transjugular intrahepatic portosystemic shunt (TIPSS) HE as well as for secondary HE prophylaxis. These findings provide support for the use of LOLA in the treatment of HE and future trials should focus on the use of LOLA for prophylaxis.
Purpose
The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, ...surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients.
Methods
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO).
Conclusion
The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.
The presence and severity of a systemic inflammatory response is a major predictor of brain edema and encephalopathy in acute liver failure (ALF) and polymorphisms of the gene coding for the ...proinflammatory cytokine TNF-alpha are known to influence the clinical outcome in ALF. Recent reports provide robust evidence for a role of neuroinflammation(inflammation of the brain
per se
) in ALF with the cardinal features of neuroinflammation including activation of microglial cells and increased production
in situ
of pro-inflammatory cytokines such as TNF-alpha and interleukins IL-1beta and IL-6. Multiple liver-brain signalling pathways have been proposed to explain the phenomenon of neuroinflammation in liver failure and these include direct effects of systemically-derived cytokines, recruitment of monocytes relating to microglial activation as well as effects of liver failure-derived toxins and altered permeability of the blood-brain barrier. Synergistic mechanisms involving ammonia and cytokines have been proposed. Currently-available strategies aimed at lowering of blood ammonia such as lactulose, probiotics and rifaximin have the potential to dampen systemic inflammation as does the anti-oxidant N-acetyl cysteine, mild hypothermia and albumin dialysis. Experimental studies demonstrate that deletion of genes coding for TNF-alpha or IL-1 leads to attenuation of the CNS consequences of ALF and administration of the TNF-alpha receptor antagonist etanercept has comparable beneficial effects in experimental ALF. Together, these findings confirm a major role for central neuroinflammatory mechanisms in general and mechanisms involving TNF-alpha in particular in the pathogenesis of the cerebral consequences of ALF and open the door to novel therapeutic interventions in this often fatal disorder.
Growing demands for temporally specific information on land surface change are fueling a new generation of maps and statistics that can contribute to understanding geographic and temporal patterns of ...change across large regions, provide input into a wide range of environmental modeling studies, clarify the drivers of change, and provide more timely information for land managers. To meet these needs, the U.S. Geological Survey has implemented a capability to monitor land surface change called the Land Change Monitoring, Assessment, and Projection (LCMAP) initiative. This paper describes the methodological foundations and lessons learned during development and testing of the LCMAP approach. Testing and evaluation of a suite of 10 annual land cover and land surface change data sets over six diverse study areas across the United States revealed good agreement with other published maps (overall agreement ranged from 73% to 87%) as well as several challenges that needed to be addressed to meet the goals of robust, repeatable, and geographically consistent monitoring results from the Continuous Change Detection and Classification (CCDC) algorithm. First, the high spatial and temporal variability of observational frequency led to differences in the number of changes identified, so CCDC was modified such that change detection is dependent on observational frequency. Second, the CCDC classification methodology was modified to improve its ability to characterize gradual land surface changes. Third, modifications were made to the classification element of CCDC to improve the representativeness of training data, which necessitated replacing the random forest algorithm with a boosted decision tree. Following these modifications, assessment of prototype Version 1 LCMAP results showed improvements in overall agreement (ranging from 85% to 90%).
•We developed a robust capability for operational monitoring of land surface change.•Landsat ARD and Continuous Change Detection and Classification are foundational.•Landsat's rich time series has substantial variability in observation frequency.•The algorithm was modified reducing variability in results between scene centers and overlap zones.•Classification was modified to improve training data representativeness and reduce artifacts.
In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the ...past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth. BPD is now recognized as the result of an aberrant reparative response to both antenatal injury and repetitive postnatal injury to the developing lungs. Consequently, lung development is markedly impaired, which leads to persistent airway and pulmonary vascular disease that can affect adult lung function. Greater insights into the pathobiology of BPD will provide a better understanding of disease mechanisms and lung repair and regeneration, which will enable the discovery of novel therapeutic targets. In parallel, clinical and translational studies that improve the classification of disease phenotypes and enable early identification of at-risk preterm infants should improve trial design and individualized care to enhance outcomes in preterm infants.
Bio-ethanol has the potential to be used as an alternative to petroleum gasoline for the purpose of reducing the total CO
2 emissions from internal combustion engines and this paper is devoted to the ...investigation of using different blending-ratios of bio-ethanol/gasoline with respect to spark timing and injection strategies. The experimental work has been carried out on a direct injection spark ignition engine at a part load and speed condition. It is shown that the benefits of adding ethanol into gasoline are reduced engine-out emissions and increased efficiency, and the impact changes with the blend ratio following a certain pattern. These benefits are attributed to the fact that the addition of ethanol modifies the evaporation properties of the fuel blend which increases the vapour pressure for low blends and reduces the heavy fractions for high blends. This is furthermore coupled with the presence of oxygen within the ethanol fuel molecule and the contribution of its faster flame speed, leading to enhanced combustion initiation and stability and improved engine efficiency.
A highly sensitive and selective nitroreductase probe, showing a rapid and strong bioluminescence enhancement (>100-fold in 5 minutes), and its initial application in the real time detection of both ...Gram positive and Gram negative live bacteria and monitoring of their growth has been reported.
Acute liver failure (ALF) due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE), a serious ...neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α) in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM) hepatotoxicity.
Mice were administered saline or etanercept (10 mg/kg; i.p.) 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001) and CD40L levels (3.7-fold; p<0.001) compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05), attenuated microglial activation (assessed by OX-42 immunoreactivity), and increased brain glutathione concentrations.
These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting liver transplantation.
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