Summary
Background
Interventional treatment for overt hepatic encephalopathy (OHE), includes non‐absorbable disaccharides, neomycin, rifaximin, L‐ornithine‐L‐aspartate and branched chain amino acids ...(BCAA). However, the optimum regimen remains inconclusive.
Aim
To compare interventions in terms of patients’ adverse events and major clinical outcomes.
Methods
Literature search of PubMed, Embase, Scopus, and Cochrane Library studies published up to July 31 2014. RCTs of above interventions in OHE patients were included. Network meta‐analysis combined direct and indirect evidence to estimate odds ratios (ORs) and mean difference (MD) between treatments and the probabilities of ranking for treatment based on clinical outcomes.
Results
Twenty eligible RCTs were included. When compared with observation, only L‐ornithine‐L‐aspartate (OR 3.71, P < 0.001) and BCAA (OR 3.37, P < 0.001) improved clinical efficacy significantly. However, when L‐ornithine‐L‐aspartate was compared with BCAA, non‐absorbable disaccharides and neomycin, there was a trend suggesting that L‐ornithine‐L‐aspartate may be the most effective intervention with respect to clinical improvement (OR 1.10), rifaximin (OR 1.31), non‐absorbable disaccharides (OR 2.75), neomycin (OR 2.22). In addition, L‐ornithine‐L‐aspartate (MD −20.18, 95% CI −40.12 to −0.27) provided a significant reduction in blood ammonia concentration compared with observation. Neomycin appeared to be associated with more adverse events in comparison with non‐absorbable disaccharides (OR 10.15), rifaximin (OR 17.31), L‐ornithine‐L‐aspartate (OR 3.16) or BCAA (OR 7.69).
Conclusions
L‐ornithine‐L‐aspartate treatment may show a trend in superiority for clinical efficacy among standard interventions for OHE. Rifaximin shows the greatest reduction in blood ammonia concentration, and treatment with neomycin demonstrates a higher probability in causing adverse effects among the five compared interventions.
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
We report the experimental generation of highly energetic carbon ions up to 48 MeV per nucleon by shooting double-layer targets composed of well-controlled slightly underdense plasma and ultrathin ...foils with ultraintense femtosecond laser pulses. Particle-in-cell simulations reveal that carbon ions are ejected from the ultrathin foils due to radiation pressure and then accelerated in an enhanced sheath field established by the superponderomotive electron flow. Such a cascaded acceleration is especially suited for heavy ion acceleration with femtosecond laser pulses. The breakthrough of heavy ion energy up to many tens of MeV/u at a high repetition rate would be able to trigger significant advances in nuclear physics, high energy density physics, and medical physics.
Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients ...remain largely unknown.
In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death.
A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010).
Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.
•We retrospectively studied clinical features of 28 severe Coronavirus Disease 2019 (COVID-19)-infected cancer patients from three hospitals in Wuhan, China.•We analysed risk factors associated with occurrence of admission to an intensive care unit, usage of mechanical ventilation, or death.•COVID-19-infected cancer patients presented poor outcomes with high occurrence of clinically severe event and mortality.•Antitumour treatment within 14 days of COVID-19 diagnosis increased the risk of developing severe events.
Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) ...aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas.
A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world.
MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance.
In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.
•MCDBT-1 had a sensitivity of 69.1% and a specificity of 98.9% in detecting six cancers.•In the real world, MCDBT-1 decreased late-stage incidence by 38.7%-46.4% and increased 5-year survival rate by 33.1%-40.4%.•In parallel, MCDBT-2 was set at a lower specificity but a higher sensitivity than MCDBT-1 and had an ideal performance.
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of ...the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
Persistent excessive sympathetic activation greatly contributes to the pathogenesis of chronic heart failure (CHF) and hypertension. Cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory ...reflex with positive feedback characteristics. Humoral factors such as bradykinin, adenosine and reactive oxygen species produced in myocardium due to myocardial ischaemia stimulate cardiac sympathetic afferents and thereby reflexly increase sympathetic activity and blood pressure. The CSAR is enhanced in myocardial ischaemia, CHF and hypertension. The enhanced CSAR at least partially contributes to the sympathetic activation and pathogenesis of these diseases. Nucleus of the solitary tract (NTS), hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla are the most important central sites involved in the modulation and integration of the CSAR. Angiotensin II, AT1 receptors and NAD(P)H oxidase‐derived superoxide anions pathway in the PVN are mainly responsible for the enhanced CSAR in CHF and hypertension. Central angiotensin‐(1‐7), nitric oxide, endothelin, intermedin, hydrogen peroxide and several other signal molecules are involved in regulating CSAR. Blockade of the CSAR shows beneficial effects in CHF and hypertension. This review focuses on the anatomical and physiological basis of the CSAR, the interaction of CSAR with baroreflex and chemoreflex, and the role of enhanced CSAR in the pathogenesis of CHF and hypertension.
The CDEX-1 experiment conducted a search of low-mass (< 10GeV/c super(2)) weakly interacting massive particles dark matter at the China Jinping Underground Laboratory using a p-type point-contact ...germanium detector with a fiducial mass of 915 g at a physics analysis threshold of 475 eVee. We report the hardware setup, detector characterization, data acquisition, and analysis procedures of this experiment. No excess of unidentified events is observed after the subtraction of the known background. Using 335.6 kg-days of data, exclusion constraints on the weakly interacting massive particle-nucleon spin-independent and spin-dependent couplings are derived.
Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho‐excitatory reflex that the ...afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension.
The aim of this study was to develop a widely accepted prognostic nomogram for extranodal NK/T-cell lymphoma, nasal-type (NKTCL). The clinical data from 1383 patients with NKTCL treated at 10 ...participating institutions between 2000 and 2011 were reviewed. A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. To contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort: stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range, 0.56-0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts. The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL.
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