Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial

Background

Perioperative fluid restriction in a variety of operations has shown improvement of: complications, recovery of gastrointestinal function and length of stay (LOS). We investigated effects of crystalloid fluid restriction in pancreatic surgery. Our hypothesis: enhanced recovery of gastrointestinal function.

Methods

In this double-blinded randomized trial, patients scheduled to undergo pancreatoduodenectomy (PD) were randomized: standard (S:10ml/kg/hr) or restricted (R:5ml/kg/hr) fluid protocols. Primary endpoint: gastric emptying scintigraphically assessed on postoperative day 7.

Results

In 66 randomized patients, complications and 6-year survival were analyzed. 54 patients were analyzed in intention to treat: 24 S-group and 30 R-group. 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis. The median gastric emptying time (T½) was 104 minutes (S-group, 95% confidence interval: 74–369) versus 159 minutes (R-group, 95% confidence interval: 61–204) (P = 0.893, NS). Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group (45% and 50%, P = 0.779, NS). The primary outcome parameter, gastric emptying time, did not show a statistically significant difference between groups.

Conclusion

A fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying. A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery.

Trial registration

ISRCTN62621488     

Predictors of High Profit and High Deficit Outliers under SwissDRG of a Tertiary Care Center

Principles

Case weights of Diagnosis Related Groups (DRGs) are determined by the average cost of cases from a previous billing period. However, a significant amount of cases are largely over- or underfunded. We therefore decided to analyze earning outliers of our hospital as to search for predictors enabling a better grouping under SwissDRG.

Methods

28,893 inpatient cases without additional private insurance discharged from our hospital in 2012 were included in our analysis. Outliers were defined by the interquartile range method. Predictors for deficit and profit outliers were determined with logistic regressions. Predictors were shortlisted with the LASSO regularized logistic regression method and compared to results of Random forest analysis. 10 of these parameters were selected for quantile regression analysis as to quantify their impact on earnings.

Results

Psychiatric diagnosis and admission as an emergency case were significant predictors for higher deficit with negative regression coefficients for all analyzed quantiles (p<0.001). Admission from an external health care provider was a significant predictor for a higher deficit in all but the 90% quantile (p<0.001 for Q10, Q20, Q50, Q80 and p = 0.0017 for Q90). Burns predicted higher earnings for cases which were favorably remunerated (p<0.001 for the 90% quantile). Osteoporosis predicted a higher deficit in the most underfunded cases, but did not predict differences in earnings for balanced or profitable cases (Q10 and Q20: p<0.00, Q50: p = 0.10, Q80: p = 0.88 and Q90: p = 0.52). ICU stay, mechanical and patient clinical complexity level score (PCCL) predicted higher losses at the 10% quantile but also higher profits at the 90% quantile (p<0.001).

Conclusion

We suggest considering psychiatric diagnosis, admission as an emergencay case and admission from an external health care provider as DRG split criteria as they predict large, consistent and significant losses.     

Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice

Holoprosencephaly (HPE) is a developmental anomaly characterized by inadequate or absent midline division of the embryonic forebrain and midline facial defects. It is believed that interactions between genes and the environment play a role in the widely variable penetrance and expressivity of HPE, although direct investigation of such effects has been limited. The goal of this study was to examine whether mice carrying a mutation in a gene encoding the bone morphogenetic protein (BMP) antagonist twisted gastrulation (Twsg1), which is associated with a low penetrance of HPE, are sensitized to retinoic acid (RA) teratogenesis. Pregnant Twsg1^+/− dams were treated by gavage with a low dose of all-trans RA (3.75 mg/kg of body weight). Embryos were analyzed between embryonic day (E)9.5 and E11.5 by microscopy and geometric morphometric analysis by micro-computed tomography. P19 embryonal carcinoma cells were used to examine potential mechanisms mediating the combined effects of increased BMP and retinoid signaling. Although only 7% of wild-type embryos exposed to RA showed overt HPE or neural tube defects (NTDs), 100% of Twsg1^−/− mutants exposed to RA manifested severe HPE compared to 17% without RA. Remarkably, up to 30% of Twsg1^+/− mutants also showed HPE (23%) or NTDs (7%). The majority of shape variation among Twsg1^+/− mutants was associated with narrowing of the midface. In P19 cells, RA induced the expression of Bmp2, acted in concert with BMP2 to increase p53 expression, caspase activation and oxidative stress. This study provides direct evidence for modifying effects of the environment in a genetic mouse model carrying a predisposing mutation for HPE in the Twsg1 gene. Further study of the mechanisms underlying these gene-environment interactions in vivo will contribute to better understanding of the pathogenesis of birth defects and present an opportunity to explore potential preventive interventions.KEY WORDS: Twisted gastrulation, Twsg1, Bone morphogenetic protein, Holoprosencephaly, Retinoic acid, Apoptosis, Oxidative stress     

Objectively Measured Daily Steps and Subsequent Long Term All-Cause Mortality: The Tasped Prospective Cohort Study

BackgroundSelf–reported physical activity has been inversely associated with mortality but the effect of objectively measured step activity on mortality has never been evaluated. The objective is to determine the prospective association of daily step activity on mortality among free-living adults.ConclusionsHigher daily step count was linearly associated with subsequent long term mortality among free living adults. These data are the first to quantify mortality reductions using an objective measure of physical activity in a free living population. They strongly underscore the importance of physical inactivity as a major public health problem.     

Two birds with one stone: Doing metabolomics with your proteomics kit

Proteomic research facilities and laboratories are facing increasing demands for the integration of biological data from multiple ‘‐OMICS’ approaches. The aim to fully understand biological processes requires the integrated study of genomes, proteomes and metabolomes. While genomic and proteomic workflows are different, the study of the metabolome overlaps significantly with the latter, both in instrumentation and methodology. However, chemical diversity complicates an easy and direct access to the metabolome by mass spectrometry (MS). The present review provides an introduction into metabolomics workflows from the viewpoint of proteomic researchers. We compare the physicochemical properties of proteins and peptides with metabolites/small molecules to establish principle differences between these analyte classes based on human data. We highlight the implications this may have on sample preparation, separation, ionisation, detection and data analysis. We argue that a typical proteomic workflow (nLC‐MS) can be exploited for the detection of a number of aliphatic and aromatic metabolites, including fatty acids, lipids, prostaglandins, di/tripeptides, steroids and vitamins, thereby providing a straightforward entry point for metabolomics‐based studies. Limitations and requirements are discussed as well as extensions to the LC‐MS workflow to expand the range of detectable molecular classes without investing in dedicated instrumentation such as GC‐MS, CE‐MS or NMR.     

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.     

Soil warming increases plant species richness but decreases germination from the alpine soil seed bank

Global warming is occurring more rapidly above the treeline than at lower elevations and alpine areas are predicted to experience above average warming in the future. Temperature is a primary factor in stimulating seed germination and regulating changes in seed dormancy status. Thus, plant regeneration from seed will be crucial to the persistence, migration and post disturbance recruitment of alpine plants in future climates. Here, we present the first assessment of the impact of soil warming on germination from the persistent alpine soil seed bank. Contrary to expectations, soil warming lead to reduced overall germination from the soil seed bank. However, germination response to soil temperature was species specific such that total species richness actually increased by nine with soil warming. We further explored the system by assessing the prevalence of seed dormancy and germination response to soil disturbance, the frequency of which is predicted to increase under climate change. Seeds of a significant proportion of species demonstrated physiological dormancy mechanisms and germination of several species appeared to be intrinsically linked to soil disturbance. In addition, we found no evidence of subalpine species and little evidence of exotic weed species in the soil, suggesting that the soil seed bank will not facilitate their invasion of the alpine zone. In conclusion, changes in recruitment via the alpine soil seed bank can be expected under climate change, as a result of altered dormancy alleviation and germination cues. Furthermore, the alpine soil seed bank, and the species richness therein, has the potential to help maintain local species diversity, support species range shift and moderate species dominance. Implications for alpine management and areas for further study are also discussed.     

Uncertainty analysis of material properties and morphology parameters in numerical models regarding the motion of lumbar vertebral segments

Abstract

The kinematics of a spinal motion segment is determined by the material properties of the soft-tissue and the morphology. The material properties can vary within subjects and between vertebral levels, leading to a wide possible range of motion of a spinal segment independently on its morphology. The goal of this numerical study was to identify the most influential material parameters concerning the kinematics of a spinal motion segment and their plausible ranges. Then, a method was tested to deduce the material properties automatically, based on a given ROM and morphology. A fully parametric finite element model of the morphology and material properties of a lumbar spinal motion segment was developed. The impact of uncertainty of twelve spinal material parameters, as well as the size of the gap between the articular surfaces of the facet joints was examined. The simulation results were compared to our own in vitro data. The flexibility of a lumbar segment was especially influenced by the properties of the anterior annulus region, the facet gap size and the interspinous ligament. The high degree of uncertainty in the material properties and facet gap size published in the literature can lead to a wide scatter in the motion of a spinal segment, with a range of 6°-17° in the intact condition in flexion/extension, from 5°-22° in lateral bending and from 3°-14° in axial rotation. Statistical analysis of the variability might help to estimate the sensitivity and total uncertainty propagated through biomechanical simulations, affecting the reliability of the predictions.     

Influence of morphology and material properties on the range of motion of the costovertebral joint – a probabilistic finite element analysis

Abstract

The motion of the costovertebral joint (CVJ) is governed by the material properties and its morphology. The goal of this numerical study was to identify the material and morphology parameters with the greatest influence on the motion of the CVJ. A fully parametric finite element model of the anatomy and material properties of the CVJ was developed. The impact of five morphology and thirteen material parameters was investigated and compared to in vitro data. The motion was influenced in particular by the rotational stiffness of the articulatio capitis costae and the lateral position of the fovea costalis transveralis.