It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames ...shorter than 24 hours has not been adequately defined.
To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0 to 23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterologic consultation. The primary end point was death from any cause within 30 days after randomization.
A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23 of 258 patients) in the urgent-endoscopy group and 6.6% (17 of 258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval CI, -2.3 to 6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI, -1.9 to 8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group.
In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterologic consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation. (Funded by the Health and Medical Fund of the Food and Health Bureau, Government of Hong Kong Special Administrative Region; ClinicalTrials.gov number, NCT01675856.).
Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and ...molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC. By RRBS, DNA promoter hypermethylation was identified in HCC from TG mice. Induction of promoter hypermethylation was associated with reduced tet methylcytosine dioxygenase 1 (TET1) expression by COX-2. TET1 could catalyze the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC) and prevents DNA hypermethylation. In keeping with this, loss of 5hmC was demonstrated in COX-2-induced HCC. Consistently, COX-2 overexpression in human HCC cell lines could reduce both TET1 expression and 5hmc levels. Integrative analyses of DNA methylation and gene expression profiles further identified significantly downregulated genes including LTBP1, ADCY5 and PRKCZ by promoter methylation in COX-2-induced HCC. Reduced expression of LTBP1, ADCY5 and PRKCZ by promoter hypermethylation was further validated in human HCCs. Bio-functional investigation revealed that LTBP1 inhibited cell proliferation in HCC cell lines, suggesting its potential role as a tumor suppressor in HCC. Gene expression microarrays revealed that signaling cascades (AKT (protein kinase B), STK33 (Serine/Threonine kinase 33) and MTOR (mechanistic target of rapamycin) pathways) were enriched in COX-2-induced HCC. In conclusion, this study demonstrated for the first time that enhanced COX-2 expression in hepatocytes is sufficient to induce HCC through inducing promoter hypermethylation by reducing TET1, silencing tumor-suppressive genes and activating key oncogenic pathways. Inhibition of COX-2 represents a mechanism-based target for HCC prevention.
Summary
Background
Tong‐Xie‐Yao‐Fang (TXYF) is a Chinese herbal formula for treating chronic diarrhoea accompanied by abdominal pain. The results were inconsistent in previous trials examining its ...effect.
Aim
To study the efficacy of TXYF granules for treating diarrhoea‐predominant irritable bowel syndrome (IBS‐D).
Methods
We performed a double‐blind, placebo‐controlled randomised trial and enrolled 160 participants with IBS‐D. The participants had VAS scores ≥3 cm in IBS‐D global symptoms and ≥2 days in a week with abdominal pain and loose stools (Bristol score 5, 6 or 7). They were randomly assigned to received TXYF or placebo during a treatment period of 4 weeks, and they were followed up for 8 weeks after treatment. The primary outcome was adequate relief of IBS‐D global symptoms for at least 2 of 4 weeks during weeks 1‐4. Secondary outcomes included mean weekly VAS scores of IBS‐D major symptoms, mean weekly stool frequency, mean weekly Bristol score, and adverse events.
Results
155 of 160 patients completed the trial. We found a significantly higher rate of adequate relief of global symptoms in TXFY group during weeks 1 to 4 (57.5% vs 37.5%, χ2 = 5.6391, P = 0.017); logistic regression analysis showed a similar result (OR 2.2, 95% CI 1.2‐4.4, P = 0.016). Most of the secondary outcomes showed superiority of TXYF over placebo in weekly assessment from week 3 to week 7. The adverse event rate was low in both groups (3.8% vs 3.8%, P = 1.000).
Conclusion
During a 4 week trial, TXFY granules were superior to placebo in controlling symptoms of IBS‐D.
Linked ContentThis article is linked to Vitta and Sayuk and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14902 and https://doi.org/10.1111/apt.14906.
Summary
Background
Bullous pemphigoid (BP) is the most common autoimmune‐mediated subepidermal blistering skin disease and is associated with significant morbidity and mortality.
Objectives
To ...determine the 3‐year mortality rate, risk factors and causes of death in patients with BP in Singapore, compared with the general population.
Methods
We conducted a retrospective cohort study of all newly diagnosed patients with BP seen at the National Skin Centre from 1 April 2004 to 31 December 2009. Demographic and clinical data on comorbidities and treatment were recorded. Mortality information was obtained from the National Registry of Diseases.
Results
In total 359 patients were included in our study. The 1‐, 2‐, 3‐year mortality rates were 26·7%, 38·4% and 45·7%, respectively. The 3‐year standardized mortality risk for patients with BP was 2·74 (95% confidence interval 2·34–3·19) times higher than for the age‐ and sex‐matched general population. Parkinson disease, heart failure and chronic renal disease were associated with increased mortality, while combination treatment with low‐to‐moderate‐dose corticoste‐roids and immunomodulatory agents such as doxycycline and/or nicotinamide was associated with lower mortality. Overall, infections were the most common cause of death (59·8%), with the main causes of death being pneumonia (42·7%), cardiovascular disease (14·6%) and stroke (11·6%).
Conclusions
This study confirms an increased 3‐year mortality rate for patients with BP in Singapore. Risk factors for increased mortality include medical comorbidities, especially neurological, cardiac and renal diseases. Treatment with combination therapy, including the use of low‐to‐moderate‐dose corticosteroid, appeared to decrease mortality risk in patients with BP.
What's already known about this topic?
Bullous pemphigoid (BP) is the most common subepidermal blistering skin disease and is associated with significant morbidity.
Patients with BP have an increased mortality rate compared with the general population in Western cohorts.
What does this study add?
This is the first comprehensive study to demonstrate increased mortality risk in Asian patients with BP.
Mortality risk factors include Parkinson disease, heart failure and chronic renal disease.
Combination treatment with low‐to‐moderate‐dose corticosteroids and immunomodulatory agents, such as doxycycline and/or nicotinamide, was associated with lower mortality.
Since the efficacy of mycophenolate mofetil (MMF) to treat immunoglobulin A (IgA) nephropathy is controversial, we extended our original study by following 40 Chinese patients with established IgA ...nephropathy for 6 years. All patients were maintained on their angiotensin blockade medication and half were randomized to receive MMF for 6 months. After 6 years, 11 patients required dialysis (2 from the MMF and 9 from the control group). Significantly, only 3 treated (as compared to 10 control) patients reached the composite end point of serum creatinine doubling or end-stage renal disease. Linear regression showed the annualized decline in the estimated glomerular filtration rate was significantly less in the MMF-treated group. Urinary protein excretion and the albumin-to-creatinine ratio were lower with MMF treatment during the first 24 months, beyond which there was no difference between groups. Multivariable Cox regression analysis showed that the baseline estimated glomerular filtration rate and proteinuria, and change in the urine albumin-to-creatinine ratio at 1 year to be important predictors of progression to end-stage renal disease. We found that among Chinese patients with IgA nephropathy who had mild histologic lesions and persistent proteinuria despite maximal angiotensin blockade, MMF treatment may result in transient and partial remission of proteinuria in the short-term and renoprotection in the long-term.
Laser scribing is an attractive reduced graphene oxide (rGO) growth and patterning technology because the process is low-cost, time-efficient, transfer-free, and flexible. Various laser-scribed rGO ...(LSG) components such as capacitors, gas sensors, and strain sensors have been demonstrated. However, obstacles remain toward practical application of the technology where all the components of a system are fabricated using laser scribing. Memory components, if developed, will substantially broaden the application space of low-cost, flexible electronic systems. For the first time, a low-cost approach to fabricate resistive random access memory (ReRAM) using laser-scribed rGO as the bottom electrode is experimentally demonstrated. The one-step laser scribing technology allows transfer-free rGO synthesis directly on flexible substrates or non-flat substrates. Using this time-efficient laser-scribing technology, the patterning of a memory-array area up to 100 cm(2) can be completed in 25 min. Without requiring the photoresist coating for lithography, the surface of patterned rGO remains as clean as its pristine state. Ag/HfOx/LSG ReRAM using laser-scribing technology is fabricated in this work. Comprehensive electrical characteristics are presented including forming-free behavior, stable switching, reasonable reliability performance and potential for 2-bit storage per memory cell. The results suggest that laser-scribing technology can potentially produce more cost-effective and time-effective rGO-based circuits and systems for practical applications.
State-of-the-art methods in the image-to-image translation are capable of learning a mapping from a source domain to a target domain with unpaired image data. Though the existing methods have ...achieved promising results, they still produce visual artifacts, being able to translate low-level information but not high-level semantics of input images. One possible reason is that generators do not have the ability to perceive the most discriminative parts between the source and target domains, thus making the generated images low quality. In this article, we propose a new Attention-Guided Generative Adversarial Networks (AttentionGAN) for the unpaired image-to-image translation task. AttentionGAN can identify the most discriminative foreground objects and minimize the change of the background. The attention-guided generators in AttentionGAN are able to produce attention masks, and then fuse the generation output with the attention masks to obtain high-quality target images. Accordingly, we also design a novel attention-guided discriminator which only considers attended regions. Extensive experiments are conducted on several generative tasks with eight public datasets, demonstrating that the proposed method is effective to generate sharper and more realistic images compared with existing competitive models. The code is available at https://github.com/Ha0Tang/AttentionGAN .
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