Hydroxyethyl starch (HES) corrected is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.
In ...this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.
Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval CI, 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.
Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).
In this study, patients with severe sepsis were assigned to fluid resuscitation with starch (HES 130/0.4) or Ringer's acetate. The starch group had an increased risk of death at day 90 and increased ...use of renal-replacement therapy, as compared with the Ringer's acetate group.
Intravenous fluids are the mainstay of treatment for patients with hypovolemia due to severe sepsis. Colloid solutions are used to obtain rapid and lasting circulatory stabilization, but there are limited data to support this practice.
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The Surviving Sepsis Campaign guidelines recommend the use of either colloids or crystalloids,
2
but high-molecular-weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis, as observed in two randomized trials.
3
,
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Those trials had substantial limitations, and participants received HES solutions with a molecular weight of 200 kD and a substitution ratio (the number of hydroxyethyl groups per glucose molecule) of . . .
Evidence-based standards in proficiency are needed for ultrasound-guided peripheral intravenous access. In this study, we explored the validity of the Peripheral Ultrasound-Guided Vascular Access ...(P-UGVA) Rating Scale.We recruited 3 groups of physicians (5 novices, 5 intermediates, and 5 experts) of increasing proficiency in peripheral ultrasound-guided intravenous access. All participants performed 3 peripheral ultrasound-guided intravenous accesses on three different patients. Performance was video-recorded by 3 cameras and the ultrasound image. Synchronized and anonymized split-screen film clips were rated using the P-UGVA rating scale by 2 assessors, which also assessed overall performance on a 1-5 Likert-scale. Evidence of validity was explored using the contemporary validity framework by Messick (content, response process, internal structure, relations to other variables, and consequences).Content and response process was ensured in the development of the rating scale and validity study. Internal consistency of the P-UGVA rating scale was excellent and sufficient high for certification purposes (Cronbach's alpha = 0.91). Proficiency groups were successfully discriminated by the UPGIVA rating scale (P = .029, one-way ANOVA), and the P-UGVA rating scale scores also correlated strongly with the overall performance evaluations (rho = 0.87, P < .001, Pearson correlation). We calculated a pass/fail score of 29, which lead to a theoretical false positive rate of 26.5% and false negative rate of 8.5%.We present validity evidence for the P-UGVA rating scale and an evidence-based standard in proficiency for ultrasound-guided peripheral intravenous access.
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•Fungal CE15 GEs were found to improve the enzymatic saccharification of corn fiber.•GEs degrade ester LCCs between lignin alcohols and glucuronic acids in xylans.•A preference for ...bulky arylalkyl substrates mimicking LCCs was observed.•GEs may act as auxiliary enzymes in enzymatic saccharification of lignocellulosics.•Hereby GEs improve access of cellulases and hemicellulases to plant poysaccharides.
Lignin-carbohydrate complexes (LCCs) are in part responsible for the recalcitrance of lignocellulosics in relation to industrial utilization of biomass for biofuels. Glucuronoyl esterases (GEs) belonging to the carbohydrate esterase family 15 have been proposed to be able to degrade ester LCCs between glucuronic acids in xylans and lignin alcohols. By means of synthesized complex LCC model substrates we provide kinetic data suggesting a preference of fungal GEs for esters of bulky arylalkyl alcohols such as ester LCCs. Furthermore, using natural corn fiber substrate we report the first examples of improved degradation of lignocellulosic biomass by the use of GEs. Improved C5 sugar, glucose and glucuronic acid release was observed when heat pretreated corn fiber was incubated in the presence of GEs from Cerrena unicolor and Trichoderma reesei on top of different commercial cellulase/hemicellulase preparations. These results emphasize the potential of GEs for delignification of biomass thereby improving the overall yield of fermentable sugars for biofuel production.
Purpose
This paper aims to explore how maintenance tasks can be planned and executed in a smarter way and, consequently, how the operations and maintenance of offshore wind power installations can be ...improved through modularisation.
Design/methodology/approach
This is a case study of one of Europe’s leading offshore wind power operators with more than 1,000 wind turbine generators in operation. By focusing on this company, in-depth insights into its operations and maintenance processes are investigated.
Findings
Lean is identified to constitute an important first step before the modularisation of maintenance tasks. The modularisation of the maintenance of offshore wind farms is identified to reduce preventive maintenance times.
Practical implications
The paper develops a process to identify the resources needed for maintenance before the modularisation of maintenance tasks and resources can take place. The authors also establish a foundation for the development of a software tool to support the development of the modularisation of maintenance tasks.
Originality/value
The present study contributes to the rather immature field of research on the operations and maintenance of offshore wind power. Furthermore, it adds to the emerging research area of service modularity.
By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with ...severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis.
The 6S trial will randomize 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%.
The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed.
ClinicalTrials.gov: NCT00962156.
The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer's Disease is commonly ...preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer's Disease-like brain pathology as observed by
C-PiB PET and
F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis.
Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being ...explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development.
We blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell intrinsic effects were further investigated
and in autoreactive mixed bone marrow chimeras.
GC block failed to curb autoimmune progression in the R848 model based on anti-dsDNA and plasma cell output, superoligomeric DNA complexes, and immune complex deposition in glomeruli. The 564Igi model confirmed this based on anti-dsDNA and plasma cell output.
, loss of Bcl-6 prevented GC B cell expansion and accelerated plasma cell differentiation. In a competitive scenario
, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output.
We identified the extrafollicular pathway as a key contributor to autoimmune progression. We propose that therapeutic targeting of low quality and poorly controlled extrafollicular responses could be a desirable strategy to curb autoreactivity, as it would leave intact the more stringently controlled and high-quality GC responses providing durable protection against infection.
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