Background
Whether continued oral feeding may have a negative impact on healing of postoperative pancreatic fistula (POPF) is unclear. The aim was to test the hypothesis that oral feeding is ...non‐inferior to enteral feeding in closure of POPF after pancreatoduodenectomy, and to clarify the effects of oral feeding on the duration and grade of POPF.
Methods
This multicentre, non‐inferiority randomized trial of oral or enteral feeding of patients with POPF after pancreatoduodenectomy recruited patients between August 2013 and September 2016. The primary efficacy outcome was the 30‐day fistula closure rate. The prespecified non‐inferiority margin was 15 per cent. Other efficacy outcomes included grade of fistula, and hospital stay and costs.
Results
A total of 114 patients were included, and received oral (57) or enteral (57) feeding. The two groups were balanced in baseline characteristics and no patient was lost to follow‐up. In intention‐to‐treat analysis, oral feeding was non‐inferior to enteral feeding in terms of 30‐day fistula closure rate (88 versus 89 per cent respectively; difference –1·8 per cent, lower limit of 95 per cent c.i. –14·4 per cent; P = 0·020 for non‐inferiority). Compared with enteral feeding, oral feeding significantly reduced hospital costs and duration of stay. No significant differences were noted in the number of patients whose POPF evolved into grade B/C, or other outcomes.
Conclusion
Oral feeding in patients with POPF after pancreatoduodenectomy did not increase the duration or grade of POPF, and was associated with reduced duration of stay and hospital costs. Registration number: NCT01755260 (http://www.clinicaltrials.gov).
Both routes equivalent
Summary
Background
The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be ...determined.
Aim
To derive and validate a combined ELF‐liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients.
Methods
Using the data of a previously reported cohort of 238 CHB patients, an ALT‐based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF‐LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported.
Results
In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve AUROC 0.83, 95% confidence interval CI 0.76–0.91 than ELF (AUROC 0.69, 95% CI 0.63–0.75). The optimal cut‐off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%).
Conclusions
An Enhanced Liver Fibrosis ‐ liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.
Introduction
Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a ...high‐performance, blood‐based test for AD.
Methods
We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high‐throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.
Results
We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage‐dependent dysregulation, which can delineate AD stages.
Discussion
This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high‐performance, blood‐based test for clinical AD screening and staging.
Background: Hemoclips, injection therapy and thermocoagulation (heater probe or electrocoagulation) are the most commonly used types of endoscopic hemostasis for the control of non-variceal ...gastrointestinal bleeding. Aim: To compare the efficacy of hemoclips versus injection or thermocoagulation in endoscopic hemostasis by pooling data from the literature. Method: Publications in the English literature (MEDLINE, EMBASE and Cochrane Library) as well as abstracts in major international conferences were searched using the keywords “hemoclips” and “bleeding”, and 15 trials fulfilling the search criteria were found. Outcome measures included: initial hemostasis (after endoscopic intervention); recurrent bleeding; definitive hemostasis (no recurrent bleeding until the end of follow-up); the requirement for surgical intervention; and all-cause mortality. The heterogeneity of trials was examined and the effects were pooled by meta-analysis. Results: Of 1156 patients recruited in the 15 studies, 390 were randomly assigned to receive clips alone, 242 received clips combined with injection, 359 received injection alone, and 165 received thermocoagulation with or without injection. Definitive hemostasis was higher with hemoclips (86.5%) than injection (75.4%; RR 1.14, 95% CI 1.00–1.30), or endoscopic clips with injection (88.5%) compared with injections alone (78.1%; RR 1.13, 95% CI 1.03–1.23), leading to a reduced requirement for surgery but no difference in mortality. Compared with thermocoagulation, there was no improvement in definitive hemostasis with clips (81.5% versus 81.2%; RR 1.00, 95% CI 0.77–1.31). These estimates were robust in sensitivity analyses. There was also no difference between clips and thermocoagulation in rebleeding, the need for surgery and mortality. The reported locations of failed hemoclip applications included posterior wall of duodenal bulb, posterior wall of gastric body and lesser curve of the stomach. Conclusion: Successful application of hemoclips is superior to injection alone but comparable to thermocoagulation in producing definitive hemostasis. There was no difference in all-cause mortality irrespective of the modalities of endoscopic treatment.
Context.
Molecular filaments and hubs have received special attention recently thanks to new studies showing their key role in star formation. While the (column) density and velocity structures of ...both filaments and hubs have been carefully studied, their magnetic field (B-field) properties have yet to be characterized. Consequently, the role of B-fields in the formation and evolution of hub-filament systems is not well constrained.
Aims.
We aim to understand the role of the B-field and its interplay with turbulence and gravity in the dynamical evolution of the NGC 6334 filament network that harbours cluster-forming hubs and high-mass star formation.
Methods.
We present new observations of the dust polarized emission at 850
μ
m toward the 2 pc × 10 pc map of NGC 6334 at a spatial resolution of 0.09 pc obtained with the
James Clerk Maxwell
Telescope (JCMT) as part of the B-field In STar-forming Region Observations (BISTRO) survey. We study the distribution and dispersion of the polarized intensity (
PI
), the polarization fraction (
PF
), and the plane-of-the-sky B-field angle (
χ
B_POS
) toward the whole region, along the 10 pc-long ridge and along the sub-filaments connected to the ridge and the hubs. We derived the power spectra of the intensity and
χ
B
POS
along the ridge crest and compared them with the results obtained from simulated filaments.
Results.
The observations span ~3 orders of magnitude in Stokes
I
and
PI
and ~2 orders of magnitude in
PF
(from ~0.2 to ~ 20%). A large scatter in
PI
and
PF
is observed for a given value of
I
. Our analyses show a complex B-field structure when observed over the whole region (~ 10 pc); however, at smaller scales (~1 pc),
χ
B
POS
varies coherently along the crests of the filament network. The observed power spectrum of
χ
B
POS
can be well represented with a power law function with a slope of − 1.33 ± 0.23, which is ~20% shallower than that of
I
. We find that this result is compatible with the properties of simulated filaments and may indicate the physical processes at play in the formation and evolution of star-forming filaments. Along the sub-filaments,
χ
B
POS
rotates frombeing mostly perpendicular or randomly oriented with respect to the crests to mostly parallel as the sub-filaments merge with the ridge and hubs. This variation of the B-field structure along the sub-filaments may be tracing local velocity flows of infalling matter in the ridge and hubs. Our analysis also suggests a variation in the energy balance along the crests of these sub-filaments, from magnetically critical or supercritical at their far ends to magnetically subcritical near the ridge and hubs. We also detect an increase in
PF
toward the high-column density (
N
H
2
≳ 10
23
cm
−2
) star cluster-forming hubs. These latter large
PF
values may be explained by the increase in grain alignment efficiency due to stellar radiation from the newborn stars, combined with an ordered B-field structure.
Conclusions.
These observational results reveal for the first time the characteristics of the small-scale (down to ~ 0.1 pc) B-field structure of a 10 pc-long hub-filament system. Our analyses show variations in the polarization properties along the sub-filaments that may be tracing the evolution of their physical properties during their interaction with the ridge and hubs. We also detect an impact of feedback from young high-mass stars on the local B-field structure and the polarization properties, which could put constraints on possible models for dust grain alignment and provide important hints as to the interplay between the star formation activity and interstellar B-fields.
The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza.
A prospective, observational cohort study was conducted over 24 ...months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates.
754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70+/-18 years; co-morbidities and serious complications were common (61-77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation.
Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.
Summary
Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. ...First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs).
Introduction
The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures.
Methods
Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis.
Results
The search yielded 19 observational studies (
n
= 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45–1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11–1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43–2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95–1.83).
Conclusions
FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.
•A stress-path dependent axial stress-strain model of FRP-confined concrete is proposed.•The model considers stress-path history of confinement by using an adjusted active confined concrete ...stress.•The model was verified by 321 test results obtained by other researchers.
High-strength concrete (HSC) has higher strength-to-weight ratio and stiffness than normal-strength concrete (NSC). Therefore, the use of HSC can decrease the construction and demolition waste and embodied carbon content of structural members that enhances the urban sustainability. However, HSC is more brittle than NSC. To further push up the maximum concrete strength limit in practical construction, confining concrete by fibre-reinforced polymer (FRP) has been advocated to restore ductility. Compared with using hollow-steel tube as confinement, FRP has lighter weight, higher tensile strength, better corrosion resistance, and is more durable and flexible. Nevertheless, it is up to now a difficult task to predict accurately the uni-axial stress-strain behaviour of FRP-confined concrete since the effect of confining stress, concrete strength, hoop and axial strains are inter-related and need to be determined simultaneously. Herein, to better understand and simulate the behaviour of FRP-confined concrete, a stress-strain model has been developed, which consists of the following three main components: (1) A hoop strain equation elaborated from the authors’ previous study on steel-confined concrete columns for application to FRP-confined concrete; (2) A modified confined concrete model considering stress-path of confining stress (or history of hoop strain); (3) Interaction between FRP and concrete. The model was verified based on 321 test results obtained from the literature, the design application of the which to a broad range of FRP-confined concrete structures is thus ensured.
Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor ...suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, suggesting an oncogenic function in advanced-stage disease. To further delineate Cav1 function in breast cancer progression, we evaluated its expression levels among a panel of cell lines representing a spectrum of breast cancer phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells, Cav1 was consistently upregulated, and positively correlated with increased cell proliferation, anchorage-independent growth, and migration and invasion. To identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described regions that flank CGIs with less CG-density. Integration of genome-wide DNA methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell lines showed that differential methylation of CGI shores, but not CGIs, significantly regulated Cav1 expression. In breast cancer cell lines having low Cav1 expression (despite promoter CGI hypomethylation), we found that treatment with a DNA methyltransferase inhibitor induced Cav1 expression via CGI shore demethylation. In addition, further methylome assessments revealed that breast cancer aggressiveness associated with Cav1 CGI shore methylation levels, with shore hypermethylation in minimally aggressive, luminal breast cancer cells and shore hypomethylation in highly aggressive, basal-like cells. Cav1 CGI shore methylation was also observed in human breast tumors, and overall survival rates of breast cancer patients lacking estrogen receptor α (ERα) negatively correlated with Cav1 expression. Based on this first study of Cav1 (a potential oncogene) CGI shore methylation, we suggest this phenomenon may represent a new prognostic marker for ERα-negative, basal-like breast cancer.
We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS).
We followed up 75 patients for 3 ...weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods.
Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days.
The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.
Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf
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