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.).
It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin.
To test that continuing ...aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases.
A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725)
A tertiary endoscopy center.
Low-dose aspirin recipients with peptic ulcer bleeding.
78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up.
The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks.
156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points 95% CI, -3.6 to 13.4 percentage points). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points CI, 3.7 to 19.5 percentage points). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points CI, 1.7 to 16.3 percentage points).
The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy.
Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.
The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody ...responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT
) and 50% (PRNT
) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT
titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT
antibody titres to decrease by half (T
) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT
and PRNT
antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.
Background
This study aimed to compare sequential treatment by transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (RFA) with partial hepatectomy for ...hepatocellular carcinoma (HCC) within the Milan criteria.
Methods
In a randomized clinical trial, patients with HCC within the Milan criteria were included and randomized 1 : 1 to the partial hepatectomy group or the TACE + RFA group. The primary outcome was overall survival and the secondary outcome was recurrence‐free survival.
Results
Two hundred patients were enrolled. The 1‐, 3‐ and 5‐year overall survival rates were 97·0, 83·7 and 61·9 per cent for the partial hepatectomy group, and 96·0, 67·2 and 45·7 per cent for the TACE + RFA group (P = 0·007). The 1‐, 3‐ and 5‐year recurrence‐free survival rates were 94·0, 68·2 and 48·4 per cent, and 83·0, 44·9 and 35·5 per cent respectively (P = 0·026). On Cox proportional hazard regression analysis, HBV‐DNA (hazard ratio (HR) 1·76; P = 0·006), platelet count (HR 1·00; P = 0·017) and tumour size (HR 1·90; P < 0·001) were independent prognostic factors for recurrence‐free survival, and HBV‐DNA (HR 1·61; P = 0·036) was a risk factor for overall survival. The incidence of complications in the partial hepatectomy group was higher than in the TACE + RFA group (23·0 versus 11·0 per cent respectively; P = 0·024).
Conclusion
For patients with HCC within the Milan criteria, partial hepatectomy was associated with better overall and recurrence‐free survival than sequential treatment with TACE and RFA. Registration number: ACTRN12611000770965 (http://www.anzctr.org.au/).
Partial hepatectomy better
The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
Summary Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding peptic ulcers. Endoscopic treatment and acid suppression with proton-pump ...inhibitors are cornerstones in the management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use antiplatelet agents, non-steroidal anti-inflammatory drugs, and anticoagulants. The management of such patients, especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise the published scientific literature about the management of patients with bleeding peptic ulcers, identify directions for future clinical research, and suggest how mortality can be reduced.
Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, ...treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.
Abstract
SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults are unclear. Here, we report SARS-CoV-2 specific T cell responses in infected adults ...and children and find that the acute and memory CD4
+
T cell responses to structural SARS-CoV-2 proteins increase with age, whereas CD8
+
T cell responses increase with time post-infection. Infected children have lower CD4
+
and CD8
+
T cell responses to SARS-CoV-2 structural and ORF1ab proteins when compared with infected adults, comparable T cell polyfunctionality and reduced CD4
+
T cell effector memory. Compared with adults, children have lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses are increased, whilst monocyte numbers are reduced, indicating rapid adaptive co-ordination of the T and B cell responses and differing levels of inflammation. Therefore, reduced prior β-coronavirus immunity and reduced T cell activation in children might drive milder COVID-19 pathogenesis.
•From 1200 telephone interviews, the COVID-19 vaccine acceptance rate was 37.2%.•Acceptance rate was the highest in adults aged 18–24 years then increased with age.•Government recommendation was the ...strongest predictive factor of vaccine acceptance.•A key obstacle of acceptance included lack of confidence on vaccine manufacturers.•These predictors provide evidence-based formulation of vaccination strategies.
Vaccines for COVID-19 are anticipated to be available by 2021. Vaccine uptake rate is a crucial determinant for herd immunity. We examined factors associated with acceptance of vaccine based on (1). constructs of the Health Belief Model (HBM), (2). trust in the healthcare system, new vaccine platforms and manufacturers, and (3). self-reported health outcomes.
A population-based, random telephone survey was performed during the peak of the third wave of COVID-19 outbreak (27/07/2020 to 27/08/2020) in Hong Kong. All adults aged ≥ 18 years were eligible. The survey included sociodemographic details; self-report health conditions; trust scales; and self-reported health outcomes. Multivariable regression analyses were applied to examine independent associations. The primary outcome is the acceptance of the COVID-19 vaccine.
We conducted 1200 successful telephone interviews (response rate 55%). The overall vaccine acceptance rate after adjustment for population distribution was 37.2% (95% C.I. 34.5–39.9%). The projected acceptance rates exhibited a “J-shaped” pattern with age, with higher rates among young adults (18–24 years), then increased linearly with age. Multivariable regression analyses revealed that perceived severity, perceived benefits of the vaccine, cues to action, self-reported health outcomes, and trust in healthcare system or vaccine manufacturers were positive correlates of acceptance; whilst perceived access barriers and harm were negative correlates. Remarkably, perceived susceptibility to infection carried no significant association, whereas recommendation from Government (aOR = 10.2, 95% C.I. 6.54 to 15.9, p < 0.001) was as the strongest driving factor for acceptance. Other key obstacles of acceptance included lack of confidence on newer vaccine platforms (43.4%) and manufacturers without track record (52.2%), which are of particular relevance to the current context.
Governmental recommendation is an important driver, whereas perceived susceptibility is not associated with acceptance of COVID-19 vaccine. These HBM constructs and independent predictors inform evidence-based formulation and implementation of vaccination strategies.
The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the ...efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis.
This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis.
A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups.
High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.
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