Αρχειοθήκη ιστολογίου

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Πέμπτη 23 Νοεμβρίου 2017

Table of Contents



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Author Index to Volume 54 (2017)

Aass N, See Grotmol KS, 889

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Editorial Board



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Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg−1h−1) in pregnant Sprague–Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages. Also, hippocampal CA1-CA3 morphology was assessed in adult animals through a Nissl stain. Results showed a disinhibition and hyperactive behavior in pubertal animals exposed to ketamine, followed in adulthood with cognitive impairments, social withdrawal, anxiety, depression, and aggressive-like behaviors. In the hippocampus, a reduction of the CA3 layer thickness was observed, without changes in cell density. These results strongly suggest a robust link between prenatal pharmacologic manipulation of NMDA receptors and schizophrenia.



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Children's anxiety symptoms and salivary immunoglobulin A: A mutual regulatory system?

Abstract

Anxiety can impact the immune system resulting in negative health outcomes. Salivary immunoglobulin A (sIgA) is a first line of defense against foreign antigens, with lowered levels indicative of weakened mucosal immunity. Little is known about how anxiety symptoms affect the diurnal rhythm of sIgA secretion, or the longitudinal transactional sequence between the two in children and adolescents. The goals of the two studies were to: (i) explore the concurrent associations between self-reported anxiety symptoms and diurnal variations of sIgA across the day using repeated daily samples of sIgA; and (ii) examine transactional relations between children's anxiety and aggregated total amount of sIgA levels across successive periods from middle childhood (Wave 1; ages 9–12) to early adolescence (Wave 2; ages 12–15), and from early to mid- adolescence (Wave 3; ages 15–18). Concurrent results showed a steeper (positive) rise in diurnal slope of sIgA from awakening to 5 hr post-awakening in children with higher anxiety. Longitudinally, higher levels of total anxiety, and specifically, worries at Wave 1 significantly predicted lower cumulative daily levels of sIgA 3 years later at Wave 2. Lowered sIgA levels at Wave 2 in turn predicted higher anxiety at Wave 3, illustrating a "vicious cycle" feedback loop. These findings broaden our understanding of the developmental links between anxiety symptoms, the immune system, and health.



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Cortisol profiles differentiated in adolescents and young adult males with fragile X syndrome versus autism spectrum disorder

Background

Fragile X syndrome (FXS) and non-syndromic autism spectrum disorder (ASD) are distinct disorders with overlapping behavioral features. Both disorders are also highly associated with anxiety with abnormal physiological regulation implied mechanistically. Some reports suggest atypical hypothalamus-pituitary-adrenal (HPA) axis function, indexed via aberrant cortisol reactivity, in both FXS and non-syndromic ASD. However, no study has compared cortisol reactivity across these two disorders, or its relationship to ASD symptom severity.

Methods

Cortisol reactivity (prior to and following a day of assessments) was measured in 54 adolescent/young adult males with FXS contrasted to 15 males with non-syndromic ASD who had low cognitive abilities.

Results

Greater ASD symptom severity was related to increased cortisol reactivity and higher levels at the end of the day, but only in the non-syndromic ASD group. Elevated anxiety was associated with increased HPA activation in the group with FXS alone.

Conclusions

Taken together, findings suggest a unique neuroendocrine profile that distinguishes adolescent/young adult males with FXS from those with non-syndromic ASD. Severity of ASD symptoms appears to be related to cortisol reactivity in the non-syndromic ASD sample, but not in FXS; while anxiety symptoms are associated with HPA activation in the FXS sample, but not in ASD despite a high prevalence of ASD, anxiety and physiological dysregulation characteristic in both populations.



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Structural malformations of the brain, eye, and pituitary gland in PHACE syndrome

PHACE syndrome is the association of segmental facial hemangiomas with congenital arterial, brain, cardiac, and ocular anomalies. Structural brain malformations affect 41–52% of PHACE patients and can be associated with focal neurologic deficits, developmental delays, and/or intellectual disability. To better characterize the spectrum of structural brain and other intracranial anomalies in PHACE syndrome, MRI scans of the head/neck were retrospectively reviewed in 55 patients from the PHACE Syndrome International Clinical Registry and Genetic Repository. All registry patients with a diagnosis of definite PHACE syndrome who had MRI scans of satisfactory quality were included. Of 55 patients, 34 (62%) demonstrated ≥1 non-vascular intracranial anomaly; structural brain malformations were present in 19 (35%). There was no difference in the prevalence of brain anomalies between genders. Brain anomalies were more likely in patients with S1 and/or S2 distribution of facial hemangioma. The most common structural brain defects were cerebellar hypoplasia (25%) and fourth ventricle abnormalities (13%). Dandy–Walker complex and malformations of cortical development were present in 9% and 7%, respectively. Extra-axial findings such as pituitary anomalies (18%) and intracranial hemangiomas (18%) were also observed. Six patients (11%) had anomalies of the globes or optic nerve/chiasm detectable on MRI. Brain malformations comprise a diverse group of structural developmental anomalies that are common in patients with PHACE syndrome. Along with brain malformations, numerous abnormalities of the pituitary, meninges, and globes were observed, highlighting the need for careful radiologic assessment of these structures in the neuroimaging workup for PHACE syndrome.



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Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45

Summary

Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta-propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female. Six presented with DEE and 1 with early onset focal seizures and profound regression. Median seizure onset was 12 months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients had magnetic resonance susceptibility-weighted imaging; blooming was noted in the globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years, consistent with iron accumulation. We show that de novo pathogenic variants are associated with a range of developmental and epileptic encephalopathies with profound developmental consequences.



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Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet

Summary

Objective

Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Inhibiting of monoacylglycerol lipase modulates synaptic activity and neuroinflammation, 2 mediators of excessive neuronal activation underlying seizures. We studied the effect of a potent and selective irreversible MAGL inhibitor, CPD-4645, on SE that was refractory to diazepam, its neuropathologic sequelae, and the mechanism underlying the drug's effects.

Methods

Diazepam-resistant SE was induced in adult mice fed with standard or ketogenic diet or in cannabinoid receptor type 1 (CB1) receptor knock-out mice. CPD-4645 (10 mg/kg, subcutaneously) or vehicle was dosed 1 and 7 h after status epilepticus onset in video–electroencephalography (EEG) recorded mice. At the end of SE, mice were examined in the novel object recognition test followed by neuronal cellloss analysis.

Results

CPD-4645 maximal plasma and brain concentrations were attained 0.5 h postinjection (half-life = 3.7 h) and elevated brain 2-AG levels by approximately 4-fold. CPD-4645 administered to standard diet–fed mice progressively reduced spike frequency during 3 h postinjection, thereby shortening SE duration by 47%. The drug immediately abrogated SE in ketogenic diet–fed mice. CPD-4645 rescued neuronal cell loss and cognitive deficit and reduced interleukin (IL)-1β and cyclooxygenase 2 (COX-2) brain expression resulting from SE. The CPD-4645 effect on SE was similar in mice lacking CB1 receptors.

Significance

MAGL represents a novel therapeutic target for treating status epilepticus and improving its sequelae. CPD-4645 therapeutic effects appear to be predominantly mediated by modulation of neuroinflammation.



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Oral keratinocytes synthesize CTACK: a new insight into the pathophysiology of the oral mucosa

Abstract

The skin-associated chemokine CTACK plays a key role in many inflammatory conditions and could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus (OLP). In the present study, we investigated by RT-PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting (FACS) the production of CTACK in oral keratinocytes, its expression in tissues from normal and OLP patients, and its role in T cell recruitment. CTACK was produced by the oral epithelium and it affects chemotaxis of memory CLA+ cells to the oral epithelium. CTACK mRNA was expressed constitutively in primary oral epithelium and was increased during pro-inflammatory IFN-γ treatment. We found a constitutive production of CTACK at a protein level in oral primary cells that increased after IFN-γ treatment. Moreover, we confirmed that CTACK attracts memory T cells and those T cells that express CLA above the level of basal migration.

This article is protected by copyright. All rights reserved.



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Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women

Abstract

Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC).

We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥ 0.8mm or Clark's level of IV and V according to history of NMSC.

We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)).

Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of subsequent melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from subsequent melanoma. This article is protected by copyright. All rights reserved.



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Bevacizumab in Combination with Different Platinum-based Doublets in the First-line Treatment for Advanced Nonsquamous Non-small-cell Lung Cancer: A Network Meta-Analysis

Abstract

Platinum-based doublet chemotherapy with or without bevacizumab is the standard treatment for untreated advanced nonsquamous non-small-cell lung cancer (NS-NSCLC). However, adding bevacizumab to chemotherapies other than paclitaxel-carboplatin is, though widely applied clinically, largely unjustified due to the lack of head-to-head data. We performed a Bayesian network meta-analysis (NMA) to address this important issue. Data of 8548 patients from 18 randomized controlled trials (RCTs) receiving six treatments including taxane-platinum (Taxane-Pt), gemcitabine-platinum (Gem-Pt), pemetrexed-platinum (Pem-Pt), taxane-platinum + bevacizumab (Taxane-Pt+B), gemcitabine-platinum + bevacizumab (Gem-Pt+B) and pemetrexed-platinum + bevacizumab (Pem-Pt+B) were incorporated into the analyses. Direct and indirect evidence of overall survival (OS) and progression-free survival (PFS) were synthesized at the hazard ratio (HR) scale and evidence of objective response rate (ORR) and serious adverse events (SAE) were synthesized at the odds ratio (OR) scale. Taxane-Pt+B showed significant advantages in OS (HR=0.79, P<0.001), PFS (HR=0.54, P<0.001) and ORR (OR=2.7, P<0.001) over Taxane-Pt with comparable tolerability (OR=3.1, P=0.08). Gem-Pt+B showed no OS benefit compared to any other treatment. No significant differences were detected between Pem-Pt+B and Pem-Pt in four outcomes. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B were ranked the first and second respectively. In conclusion, in the first-line treatment for advanced NS-NSCLC, Taxane-Pt and Gem-Pt are the most and least preferable regimens to be used with bevacizumab, respectively. Adding bevacizumab to Pem-Pt remains unjustified because it fails to improve efficacy or tolerability. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B are the best and second-best treatment for this population. This article is protected by copyright. All rights reserved.



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Cause-specific mortality in HPV+ and HPV− oropharyngeal cancer patients: insights from a population-based cohort

Abstract

Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow-up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients.

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Identifying cause of death in oropharyngeal cancer patients may aid in optimizing follow-up and therapeutic strategies, but studies stratified on HPV status is lacking. We report cause-specific mortality in a population-based cohort of oropharyngeal cancer patients from 2000 to 2014.



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Stochastic phenotype switching leads to intratumor heterogeneity in human liver cancer

Abstract

Intratumor heterogeneity is increasingly recognized as a major factor impacting diagnosis and personalized treatment of cancer. We characterized stochastic phenotype switching as a novel mechanism contributing to intratumor heterogeneity and malignant potential of liver cancer. Clonal analysis of primary tumor cell cultures of a human sarcomatoid cholangiocarcinoma identified different types of self-propagating sub-clones characterized by stable (keratin-7 positive or keratin-7 negative) phenotypes and an unstable phenotype consisting of mixtures of keratin-7 positive and negative cells, which lack stem cell features but may reversibly switch their phenotypes. Transcriptome sequencing and immunohistochemical studies with the markers Zeb1 and CD146/MCAM demonstrated that switching between phenotypes is linked to changes in gene expression related but not identical to epithelial-mesenchymal transition. Stochastic phenotype switching occurred during mitosis and did not correlate with changes in DNA methylation. Xenotransplantation assays with different cellular sub-clones demonstrated increased tumorigenicity of cells showing phenotype switching, resulting in tumors morphologically resembling invasive component of primary tumor and metastasis. Conclusion. Our data demonstrate that stochastic phenotype switching contributes to intratumor heterogeneity and that cells with a switching phenotype have increased malignant potential. This article is protected by copyright. All rights reserved.



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Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for hepatoma invasion and metastasis

Abstract

High invasiveness is a hallmark of human hepatocellular carcinoma (HCC). Large tumors predict invasion and metastasis. Epithelial-mesenchymal transition (EMT) is crucial for cancer invasion and metastasis. However, the mechanisms whereby large tumors tend to undergo EMT remain unclear. We conducted a subgenome-wide screen and identified KLHL23 as an HCC invasion suppressor via inhibiting EMT. KLHL23 binds to actin and suppresses actin polymerization. KLHL23 silencing induced filopodium and lamellipodium formation. Moreover, EMT suppressed by KLHL23 through its action on actin dynamics. Traditionally, actin cytoskeleton remodeling is downstream of EMT reprogramming. It is, therefore, intriguing to ask why and how KLHL23 inversely regulates EMT. Activation of actin cytoskeleton remodeling by either KLHL23 silencing or treatment with actin cytoskeleton modulators augmented cellular hypoxic responses in a cell density-dependent manner resulting in HIF and Notch signals and subsequent EMT. Environmental hypoxia did not induce EMT unless actin cytoskeleton remodeling was simultaneously activated and only when cells were at high density. The resulted EMT was reversed by either adenosine 5'-triphosphate supplementation or actin polymerization inhibitors. Downregulation of KLHL23 was associated with invasion, metastasis, and poor prognosis of HCC and pancreatic cancer. Correlations of tumor size with EMT and inverse association of the expression of KLHL23 with HIF-/Notch-signals were further validated in patient-derived xenograft HCCs in mice. Conclusion: Simultaneously activation of actin cytoskeleton remodeling by intrinsic (such as KLHL23 downregulation) or microenvironment cues is crucial for cell density-dependent and hypoxia-mediated EMT, providing a mechanistic link between large tumor size and invasion/metastasis. Our findings open a new door to develop the prevention and treatment strategies for tumor invasion and metastasis. This article is protected by copyright. All rights reserved.



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HIF-1α/IL-1β signaling enhances hepatoma epithelial-mesenchymal transition via macrophages in a hypoxic-inflammatory microenvironment

ABSTRACT

The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood. We found that tumor-associated macrophages (TAMs), the primary pro-inflammatory cells within tumors, secreted more interleukin (IL)-1β under moderate hypoxic conditions due to increased stability of hypoxia inducible factor (HIF)-1α. Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by TAMs with an M2 phenotype. We further confirmed that the necrotic debris-induced IL-1β secretion was mediated via the TLR4/TRIF/NF-κB signaling in a similar but not identical fashion as lipopolysaccharide-induced inflammation. Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion. Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells via cyclooxygenase-2. The epithelial-mesenchymal transition (EMT) of HCC cells was enhanced by overexpression of HIF-1α. We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients. Conclusion: Our findings revealed a HIF-1α/IL-1β signaling loop between cancer cells and TAMs in a hypoxic microenvironment, resulting in cancer cell EMT and metastasis. More importantly, our results suggest a potential role of anti-inflammatory strategy in HCC treatment. This article is protected by copyright. All rights reserved.



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Peptic ulcer bleeding in cirrhotic patients: Is as bad as variceal bleeding?

Abstract

Peptic ulcer bleeding (PUB) is among the most common causes of hospitalization worldwide, however, advances in endoscopic and pharmacological therapies have reduced the case fatality rate to 2.1% (1). In contrast, 6-week mortality of acute variceal bleeding (AVB) remained as high as 20% (2-3). Despite the considerable incidence of peptic ulcers with 6-33% and high recurrence rate of PUB in patients with cirrhosis (4), the specific mechanisms responsible for peptic ulcers remain largely unknown in the setting of cirrhosis (4). This article is protected by copyright. All rights reserved.



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Comparison of the gut microbiota composition between wild and captive sika deer (Cervus nippon hortulorum) from feces by high-throughput sequencing

The gut microbiota is characterized as a complex ecosystem that has effects on health and diseases of host with the interactions of many other factors together. Sika deer is the national level for the protecti...

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Stroke-like migraine attacks after radiation therapy: A misnomer?

Summary

Objective

To understand the frequency of electrographic and clinical seizures in patients with stroke-like migraine attacks after radiation therapy (SMART), and determine whether SMART warrants comprehensive electroencephalographic (EEG) monitoring and aggressive seizure management.

Methods

We searched our magnetic resonance brain imaging report database for all patients between January 2013 and December 2015 for suspected SMART syndrome. Clinical inclusion criteria were further applied as follows: inpatient adults (>18 years of age) with history of cranial radiation presenting with acute neurologic deficits as primary admission reason who lacked evidence of recurrent or new brain malignancy, stroke, or infectious agents in cerebrospinal fluid. Six patients were identified. All 6 patients underwent prolonged video EEG monitoring as part of our standard protocol.

Results

All patients but 1 were found to have multiple or prolonged electrographic seizures consistent with status epilepticus during video EEG monitoring. Their neurological deficit and/or mental status change improved in parallel with resolution of the seizure activity.

Significance

SMART is likely a misnomer that underestimates the significance of seizures and status epilepticus in the pathophysiology and clinical presentation of the syndrome. Systematic continuous EEG monitoring and appropriate seizure management is warranted to reduce symptom duration and optimize clinical outcome.



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Management of Acute Hip Fracture

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Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage. A 65-year-old…

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Genome sequencing and analysis of the first spontaneous Nanosilver resistant bacterium Proteus mirabilis strain SCDR1

P. mirabilis is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In add...

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Computational predictions of damage propagation preceding dissection of ascending thoracic aortic aneurysms

Summary

Dissections of ascending thoracic aortic aneurysms (ATAA) cause significant morbidity and mortality worldwide. They occur when a tear in the intima-media of the aorta permits the penetration of the blood and the subsequent delamination and separation of the wall in two layers, forming a false channel. In order to predict computationally the risk of tear formation, stress analyses should be performed layer-specifically and they should consider internal or residual stresses which exist in the tissue. In the present paper, we propose a novel layer–specific damage model based on the constrained mixture theory (CMT) which intrinsically takes into account these internal stresses and which can predict appropriately the tear formation. The model is implemented in finite-element commercial software Abaqus coupled with user material subroutine (UMAT). Its capability is tested by applying it to the simulation of different exemplary situations, going from in vitro bulge-inflation experiments on aortic samples to in vivo over-pressurizing of patient-specific ATAAs. The simulations reveal that damage correctly starts from the intimal layer (luminal side) and propagates across the media as a tear, but never hits the adventitia. This scenario is typically the first stage of development of an acute dissection, which is predicted for pressures of about 2.5 times the diastolic pressure by the model after calibrating the parameters against experimental data carried out on collected ATAA samples. Further validations on a larger cohort of patients should hopefully confirm the potential of the model in predicting patient-specific damage evolution and possible risk of dissection during aneurysm growth for clinical applications.



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Anticholinesterase and antioxidant potentials of Nonea micrantha Bioss. & Reut along with GC-MS analysis

Nonea micrantha Boiss. & Reut . being an unexplored member of Boraginaceae was investigated for GC/MS analysis, acetylcholinesterase (AChE), butyrylcholinest...

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In vivo screening and evaluation of four herbs against MRSA infections

Recently, we reported high in vitro antibacterial efficacy of Althaea officinalis, Ziziphus jujuba, Cordia latifolia and Thymus vulgaris out of a total 21 plants against wide range of bacteria including MRSA. Thi...

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Aster koraiensis extract prevents diabetes-induced retinal vascular dysfunction in spontaneously diabetic Torii rats

Aster koraiensis extract (AKE) is a standard dietary herbal supplement. The aim of this study is to investigate the inhibitory effects of AKE on diabetes-induced retinal vascular dysfu...

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Predictors of a follicular nodule (Thy3) outcome of thyroid fine needle aspiration cytology among Saudi patients

A retrospective study was performed to evaluate predictors of thyroid fine needle aspiration cytology (FNAC) outcomes among Saudis with a thyroid nodule. Socio-demographic data, thyroid function status, thyroi...

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Exponential distribution of total depressive symptom scores in relation to exponential latent trait and item threshold distributions: a simulation study

Total depressive symptom scores in the general population have been reported to follow an exponential distribution except at the lowest end of the range of scores. To verify the hypothesis that total depressiv...

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The mediating factors in the relationship between lower urinary tract symptoms and health-related quality of life

An earlier study found that mental health partially mediates the relationship between lower urinary tract symptoms (LUTS) severity and health-related quality of life (HRQOL). In other words, LUTS adversely aff...

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Extracellular cathepsin L stimulates axonal growth in neurons

Cathepsin L, a lysosomal endopeptidase expressed in most eukaryotic cells, is a member of the papain-like family of cysteine proteases. Although commonly recognized as a lysosomal protease, cathepsin L is also...

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Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study



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MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer



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HER2 expression patterns in paired primary and metastatic endometrial cancer lesions



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Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy



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Is It Necessary to Heat and Humidify Respiratory Gases for Resuscitation in Preterm Infants?

In this volume of The Journal, McGrory et al report the results of a well-designed multicenter randomized controlled trial designed to determine whether the use of heated and humidified gases for respiratory support during the stabilization and transport of infants <30 weeks of gestational age in the delivery room reduces the rate of hypothermia on admission to the neonatal intensive care unit.1 Fewer infants in the heated and humidified respiratory gases group were hypothermic on admission to the neonatal intensive care unit (36 of 132 or 27%) compared with controls (61 of 141 or 43%, P < .01).

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Infants Born with Down Syndrome: Burden of Disease in the Early Neonatal Period

To evaluate the incidence of direct admission of infants with Down syndrome to the postnatal ward (well newborn nursery) vs the neonatal intensive care unit (NICU), and to describe the incidence of congenital heart disease (CHD) and pulmonary hypertension (PH).

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Prescription of secondary preventive drugs after ischemic stroke: results from the Malaysian National Stroke Registry

Evaluation of secondary stroke prevention in low and middle-income countries remains limited. This study assessed the prescription of secondary preventive drugs among ischemic stroke patients upon hospital dis...

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Brainstem Injury in Pediatric Patients with Posterior Fossa Tumors Treated with Proton Beam Therapy and Associated Dosimetric Factors

Controversy exists as to whether proton radiotherapy has been associated with higher rates of symptomatic brainstem injury in pediatric patients with CNS tumors. This study includes the highest risk patients with posterior fossa tumors treated with tri-modality therapy. The 5-year cumulative incidence of injury is 2%, comparable to patients treated in the photon setting. Symptomatic brainstem injury is rare when the Dmax and V55 are kept below 55.8 GyRBE and 6%, respectively

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Radiation Dose to the Thoracic Vertebral Bodies is Associated with Acute Hematologic toxicities in Patients Receiving Concurrent Chemoradiation for Lung Cancer: Results of a Single Center Retrospective Analysis

Hematologic toxicities are a common acute side effect of concurrent chemoradiation therapy in patients with lung cancer. In this study, we demonstrate an association between radiation dose to the thoracic vertebral bodies and the development of acute hematologic toxicities, which suggests that bone marrow sparing radiation methods may be used to reduce the incidence of hematologic toxicities in these patients.

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Excellent Outcomes of Liver Transplantation Following Down Staging of Hepatocellular Carcinoma to Within Milan Criteria—a Multi-Center Study

Single-center studies have reported excellent outcomes of patients who underwent liver transplantation for hepatocellular carcinoma (HCC) after successful down-staging (reduction of tumor burden with local-regional therapy), but multi-center studies are lacking. We performed a multi-center study, applying a uniform down-staging protocol, to assess outcomes of liver transplantation and performed an intention to treat analysis. We analyzed factors associated with treatment failure, defined as dropout from the liver transplant waitlist due to tumor progression, liver-related death without transplant, or recurrence of HCC after transplant.

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Factors That Contribute to Indeterminate Results from the QuantiFERON-TB Gold in-tube Test in Patients With Inflammatory Bowel Disease

The QuantiFERON-tuberculosis gold in-tube (QFT-GIT) test is widely used to screen for latent Mycobacterium tuberculosis infection in patients with inflammatory bowel diseases (IBD) before treatment with a tumor necrosis factor antagonist. The test frequently produces indeterminate results, prompting additional testing. We evaluated factors associated with indeterminate results from the QTF-GIT test among patients with IBD.

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Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy, Published online: 23 November 2017; doi:10.1038/bjc.2017.414

Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy

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MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer, Published online: 23 November 2017; doi:10.1038/bjc.2017.387

MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer

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HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

HER2 expression patterns in paired primary and metastatic endometrial cancer lesions, Published online: 23 November 2017; doi:10.1038/bjc.2017.422

HER2 expression patterns in paired primary and metastatic endometrial cancer lesions

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Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study, Published online: 23 November 2017; doi:10.1038/bjc.2017.413

Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

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Conditional Knockdown of Gene Expression in Cancer Cell Lines to Study the Recruitment of Monocytes/Macrophages to the Tumor Microenvironment

This protocol serves as a scheme for setting up a functional Tet-ON system in cancer cell lines and its subsequent use, in particular for studying the role of tumor cell-derived proteins in recruitment of monocytes/macrophages to the tumor microenvironment.

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Hypothermia indices among severely injured trauma patients undergoing urgent surgery: A single-centred retrospective quality review and analysis

Publication date: Available online 23 November 2017
Source:Injury
Author(s): A. Alam, Rafael Olarte, Jeannie Callum, Arsham Fatahi, B. Nascimento, Claude Laflamme, Robert Cohen, Avery B. Nathens, Homer Tien
BackgroundHypothermia (<36°C) exacerbates trauma-induced coagulopathy and worsens morbidity and mortality among severely injured trauma patients; there is a paucity of published data describing how well trauma centres adhere to standards regarding measurement of temperature, and best practices for preventing and treating hypothermia.MethodsWe completed a retrospective quality audit of all severely injured trauma patients (ISS≥20) who had urgent surgery at Sunnybrook Health Sciences Centre (SHSC) between 2010-2014. Information regarding temperature monitoring was evaluated over the course of the initial resuscitation and admission. Independent risk factors for in-hospital mortality were elucidated through a multivariable regression analysis.ResultsOut of a total of 4492 trauma patients, 495 were severely-injured and went to the operating room (OPR) after being treated in the trauma bay (TB) at SHSC between 2010-2014. The majority of the patients were male (n=384, 77.6%) and had a blunt mechanism of injury (n=391, 79.0%). The median ISS score was 29 (interquartile range (IQR) 26, 35). Eighty-nine (17.9%) patients died; 26 (5.2%) of these patients died intra-operatively. Less than one fifth of patients (n=82,16.6%) received a temperature measurement during pre-hospital transport phase. Upon arrival to the TB, almost two-thirds (n=301, 60.8%) of patients had their temperature recorded and a similar proportion (n=175, 58.1%) of those patients were hypothermic (<36°C). In the OPR, close to 80% (n=389, 78.6%) of patients had their temperature measured on both arrival; almost 60% (n=223, 57.3%) were hypothermic on arrival. Almost all patients had their temperature measured upon arrival to the ICU or specialized ward (n=450, 98.3%). Warming initiatives were documented in only 36 (7.3%) patients in the TB, yet documented in almost all patients in OR (n=464, 93.7%). An increased risk of in-hospital mortality was correlated with not taking a temperature measurement in the TB (Odds Ratio (OR) 2.86 (95% Confidence Interval (CI) [1.64-4.99]) or OPR (OR 4.66 (95% CI [2.50-8.69]).ConclusionsA majority of severely injured trauma patients are hypothermic well into the perioperative period after initial admission. An absence of having temperature measurement during initial hospitalization is associated with increased in-hospital mortality amongst this patient group. Quality improvement initiatives should aim to strive for ongoing temperature measurement as a key performance indicator and early prevention and treatment of hypothermia during initial resuscitation.



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The Development and Implementation of a Layperson Trauma First Responder Course in La Paz, Bolivia: A Pilot Study

Publication date: Available online 22 November 2017
Source:Injury
Author(s): Marissa A. Boeck, Tyler E. Callese, Sarah K. Nelson, Steven J. Schuetz, Christian Fuentes Bazan, Juan Mauricio P. Saavedra Laguna, Michael B. Shapiro, Nabil M. Issa, Mamta Swaroop
BackgroundNinety percent of nearly five million annual global injury deaths occur in low- and middle-income countries (LMICs), where prehospital care systems are frequently rudimentary or nonexistent. The World Health Organization considers layperson first-responders as essential for emergency medical services in low-resource settings lacking more formalized systems. This study sought to develop and implement a layperson trauma first responder course (TFRC) in Bolivia.Materials and methodsIn March and April 2013 nine sessions of the eight-hour TFRC were held in La Paz, Bolivia. The course charged a nominal fee, and was led by an American surgeon and medical student. The TFRC built upon existing models with local stakeholder input, and included both didactic and practical components. Participants completed a baseline survey, and pre and posttests. The primary outcome was test performance, with secondary outcomes including demographic sub-group test score analyses and exam question validation. Data were assessed using nonparametric and psychometric methodsResultsOne hundred fifty-nine individuals met study inclusion criteria. Participant median age was 28 (IQR 24, 36), 49.1% were male, 59.1% worked in a medical field, most had secondary (35.2%) or university (56.0%) level educations, and 67.3% had prior first aid training. Median test scores improved after course completion (48% vs. 76%, p <0.001), along with skill confidence (4 vs. 4.5, p <0.001). Most questions had appropriate item difficulty indices, point bi-serial correlation coefficients, and positive Pretest Posttest Difference Indices. Cronbach alpha coefficients for pre and posttest scores were 0.72 and 0.78, respectively.ConclusionsThis study presents data from the first offering of an original TFRC for laypeople in Bolivia. Increased participant knowledge and skill confidence after course completion, and acceptable overall psychometric test properties, indicate this model is valid and effective. Future aims include TFRC revision, and enrollment of more layperson first responders to increase population-level impacts.



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CaP Cement is equivalent to Iliac Bone Graft in Filling of Large Metaphyseal Defects: 2 Year Prospective Randomised Study on Distal Radius Osteotomies

Publication date: Available online 22 November 2017
Source:Injury
Author(s): Mona I. Winge, Magne Røkkum
The purpose of this prospective randomised study was to compare the clinical and radiological outcomes of injectable CaP bone cement with corticocancellous bone graft used to fill voids after corrective opening wedge osteotomies in the distal radius. 17 women/3 men, median age 56 (51.3; 61.0), underwent an open-wedge osteotomy of a dorsal malunion in the distal radius randomised to filling the defect either with bone graft (10) or CaP bone cement (10). Dorsal titanium locking plates were used and the wrist was plastered for 8 weeks. Follow-ups for 24 months included X-rays, CT scans, VAS on wrist and iliac crest, grip strength, ROM, Quick-DASH and Gartland & Werley scores. No difference was found between the 2 groups as to clinical outcome or radiological results with no loss of reduction. One bone graft patient developed a pseudarthrosis and one CaP patient suffered a plate fracture 6 months post-operatively. CaP bone cement is a good alternative to bone graft as a void filler in open-wedge osteotomies of the distal radius. The procedure is shorter, easier with the post-operative advantage of no donor site pain.Level of Evidence Randomised controlled trial. Level I evidence.



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Intraoperative lateral wall fractures during Dynamic Hip Screw fixation for intertrochanteric fractures-Incidence, causative factors and clinical outcome

Publication date: Available online 21 November 2017
Source:Injury
Author(s): Annur R. Pradeep, Addala KiranKumar, Jayaramaraju Dheenadhayalan, Shanmuganathan Rajasekaran
IntroductionThe intact lateral wall plays a key role in stabilization of trochanteric fracture. Hence extreme precaution should be taken to prevent lateral wall damage during DHS fixation. Present study is aimed at evaluating the determinants of lateral wall fracture and its effect on outcome in intertrochanteric fracture femur treated with DHS.Material and methodsThis is a prospective study involving intertrochanteric fractures treated with DHS fixation from July 2013 to June 2014. Out of 135 patients 49(36.3%) had stable fractures and 86(63.7%) unstable fractures. Cortical thickness index (CTI) was measured to evaluate osteoporosis. Lateral wall thickness in anteroposterior radiograph was also measured.All patients underwent 135° DHS fixation.Postoperative x-rays are assessed for implant position, intactness of the lateral wall, tip apex distance (TAD) and medialization. Functional outcome was measured at the end of fracture union by modified Harris hip score and Parkers mobility score. Clinical information including age, gender, fracture classification, TAD, lateral wall thickness and functional outcome of the patients were subjected to statistical analysis.Results34 (19.5%) patients had lateral wall fractures. Medialization was found in 22 out of these 34 (64.7%) patients. The mean preoperative lateral wall thickness of these patients is 19.2mm, compared with 26.8mm in patients with intact lateral wall (p<0.001). The mean values of CTI and TAD are comparable in both the groups. In patients with intact lateral wall, mean Harris hip score is 73.1 compared to 65.5 in lateral wall fracture group (p<0.001). Preinjury mobility status was achieved in 70.2% of intact lateral wall patients, whereas only 32.3% (11) achieved that in lateral wall fracture group. Threshold for lateral wall thickness that could predict lateral wall fracture was found to be 21mm with 95% sensitivity and 88.2% specificity.ConclusionLateral wall fractures during DHS fixation are not uncommon and osteoporosis has no bearing on its occurrence. It alone can lead to poor radiological and functional outcome independent of TAD. Lateral wall thickness is a reliable predictor of intra operative lateral wall fracture during DHS fixation and nailing is a good option especially when lateral wall thickness is <21mm.



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The value of ‘binder-off’ imaging to identify occult and unexpected pelvic ring injuries

Publication date: Available online 21 November 2017
Source:Injury
Author(s): James Anthony Charles Fagg, Mehool R. Acharya, Tim J.S. Chesser, Anthony J. Ward
AimsTo determine the effectiveness of 'binder-off' plain pelvic radiographs in the assessment of pelvic ring injuries.Patients and MethodsAll patients requiring operative intervention at our tertiary referral pelvic unit/major trauma centre for high-energy pelvic injuries between April 2012 and December 2014 were retrospectively identified. Pre-operative pelvic imaging with and without pelvic binder was reviewed with respect to fracture pattern and pelvic stability. The frequency with which the imaging without pelvic binder changed the opinion of the pelvic stability and need for operative intervention, when compared with the computed tomography (CT) scans and anteroposterior (AP) radiographs with the binder on, was assessed.ResultsSeventy-three percent (71 of 97) of patients had initial imaging with a pelvic binder in situ. Of these, 76% (54 of 71) went on to have 'binder-off' imaging. Seven percent (4 of 54) of patients had unexpected unstable pelvic ring injuries identified on 'binder-off' imaging that were not identified on CT imaging in binder.ConclusionsTrauma CT imaging of the pelvis with a pelvic binder in place is inadequate at excluding unstable pelvic ring injuries, and, based on the original findings in this paper, we recommend additional plain film 'binder-off' radiographs, when there is any clinical concern.



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Early transfusion on battlefield before admission to role 2: A preliminary observational study during “Barkhane” operation in Sahel

Publication date: Available online 23 November 2017
Source:Injury
Author(s): V. Vitalis, C. Carfantan, A. Montcriol, S. Peyreffite, A. Luft, T Pouget, A. Sailliol, S. Ausset, E. Meaudre, J. Bordes
IntroductionHaemorrage is the leading cause of death after combat related injuries and bleeding management is the cornerstone of management of these casualties. French armed forces are deployed in Barkhane operation in the Sahel-Saharan Strip who represents an immense area. Since this constraint implies evacuation times beyond doctrinal timelines, an institutional decision has been made to deploy blood products on the battlefield and transfuse casualties before role 2 admission if indicated. The purpose of this study was to evaluate the transfusion practices on battlefield during the first year following the implementation of this policy.Materials and methodsprospective collection of data about combat related casualties categorized alpha evacuated to a role 2. Battlefield transfusion was defined as any transfusion of blood product (red blood cells, plasma, whole blood) performed by role 1 or Medevac team before admission at a role 2. Patients' characteristics, battlefield transfusions' characteristics and complications were analysed.ResultsDuring the one year study, a total of 29 alpha casualties were included during the period study. Twenty-eight could be analysed, 7/28 (25%) being transfused on battlefield, representing a total of 22 transfusion episodes. The most frequently blood product transfused was French lyophilized plasma (FLYP). Most of transfusion episodes occurred during medevac. Compared to non-battlefield transfused casualties, battlefield transfused casualties suffered more wounded anatomical regions (median number of 3 versus 2, p=0.04), had a higher injury severity score (median ISS of 45 versus 25, p=0,01) and were more often transfused at role 2, received more plasma units and whole blood units. There was no difference in evacuation time to role 2 between patients transfused on battlefield and non-transfused patients. There was no complication related to battlefield transfusions. Blood products transfusion onset on battlefield ranged from 75min to 192min after injury.ConclusionBattlefield transfusion for combat-related casualties is a logistical challenge. Our study showed that such a program is feasible even in an extended area as Sahel-Saharan Strip operation theatre and reduces time to first blood product transfusion for alpha casualties. FLYP is the first line blood product on the battlefield.



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Complications and patient-injury after ankle fracture surgery. −A closed claim analysis with data from the Patient Compensation Association in Denmark

Publication date: Available online 21 November 2017
Source:Injury
Author(s): Naja Bjørslev, Lars Bo Ebskov, Camilla Mersø, Christian Wong
BackgroundThe Patient Compensation Association (PCA) receives claims for financial compensation from patients who believe they have sustained damage from their treatment in the Danish health care system. In this study, we have analysed closed claims in which patients suffered injuries due to the surgical treatment of their ankle fracture. We identified causalities contributing to these injuries and malpractices, as well as the economic consequences of these damages.MethodsFifty-one approved closed claims from the PCA database from the years 2004–2009 were analysed in a retrospective systematic review. All patients were adults with an iatrogenic injury, and received compensation. A root cause analysis was performed to identify whether the patient suffered the damage preoperatively, during surgery or postoperatively, and to determine the level of education of the injurious doctor. Economic compensation, co-morbidities and end-result complications were registered.ResultsIn 9 of the cases the injuries happened preoperatively, but the majority of the injuries, namely 34 occurred during surgery. In 21 of the cases the damage happened postoperatively. Thirty percentages of the patients were mistreated in more than one phase. Level of competence was medical specialists in 2/3 and junior doctors in 1/3 of the cases. In the preoperative phase both groups were equally responsible for the inflicted damage. In the perioperative- and postoperative group, medical specialists inflicted the majority of damages. General recommendations regarding ORIF were not followed in 21/49 of the perioperative damages. The pronation fracture was the most common. The patients received a total average compensation of 17.561 USD each.ConclusionManaging the complex ankle fracture, requires considerable experience. This study indicates that extra attention should be paid to the most technically demanding fractures as the pronation-external-rotation-, diabetic- and fragility fractures. Surgeons should follow the recommendations for ORIF. Emphasis should also focus on adequate postoperative plans. This study finds a high readmission-burden, re-operation rate and great expenses in form of compensation.



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Outcomes after resection versus non-resection management of penetrating grade III and IV pancreatic injury: A trauma quality improvement (TQIP) databank analysis

Publication date: Available online 21 November 2017
Source:Injury
Author(s): Shahin Mohseni, Jeremy Holzmacher, Gabriel Sjolin, Rebecka Ahl, Babak Sarani
BackgroundHigh-grade traumatic pancreatic injuries are associated with significant morbidity and mortality. Non-resection management is associated with fewer complications in pediatric patients. The present study evaluates outcomes following resection versus non-resection management of severe pancreatic injury caused by penetrating trauma.MethodsA retrospective study of the Trauma Quality Improvement Program (TQIP) database was performed from 1/2010 to 12/2014. Patients with AAST Organ Injury Scale pancreatic grade III and IV injuries caused by penetrating trauma were included in the study. Demographics, vital signs on admission, Abbreviated Injury Scale per body region, Injury Severity Score, transfusion and therapeutic modality were obtained. Mortality, length of stay (LOS), pseudocyst, pancreatitis, sepsis, thromboembolism, renal failure, ARDS and unplanned ICU admission or re-operation were stratified according to injury grade and treatment modality. Patients were stratified into those who did/did not undergo pancreatic resection.ResultsA total of 4,098 patients had a pancreatic injury of which 15.9% (n=653) had a grade III and 6.7% (n=274) a grade IV pancreatic injury. There were no differences in patient demographics or overall injury severity between the resected and non-resected cohorts within each pancreatic injury grade. Forty-two percent of grade III and 38.0% of grade IV injuries underwent pancreatic resection. The total LOS was longer in the resection arm irrespective of pancreatic injury severity. There was no significant difference in morbidity between cohorts. Similarly, mortality was not significantly different between the two management approaches for grade III: 15.1% (95% CI 11.0–19.9) vs. 18.4% (95% CI 14.6–22.6), p=0.32 and grade IV: 24.0% (95% CI: 16.2–33.4) vs. 27.1% (95% CI: 20.5–34.4), p=0.68.ConclusionResection for treatment of grade III and IV pancreatic injury is not associated with a significant decrease in mortality but is associated with an increase in hospital LOS.



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Optimizing intraoperative imaging during proximal femoral fracture fixation – a performance improvement program for surgeons

Publication date: Available online 21 November 2017
Source:Injury
Author(s): Daniel Rikli, Sabine Goldhahn, Michael Blauth, Samir Mehta, Michael Cunningham, Alexander Joeris
IntroductionFormal training for surgeons regarding intraoperative imaging is lacking. This project investigated the effect of an educational intervention focusing on obtaining and assessing a standardized lateral view of the proximal femur during intramedullary nailing of a pertrochanteric fracture.Materials and MethodsAnatomical landmarks of the proximal femur that can be identified using intraoperative fluoroscopy and criteria for image quality, i.e. quality of projection were defined in a consensus process, followed by the development of educational materials and a 7-item checklist. Five surgeons from 5 Trauma Centers in 4 countries participated. Each surgeon a) assessed 5 of their own retrospective cases and 5 retrospective cases from 4 colleagues from their clinic, b) viewed an educational video and poster and re-assessed the same cases, and c) assessed the intraoperative images of 5 prospectively collected consecutive cases of their own and of colleagues afterwards.ResultsThe percentage of positive ratings for image quality increased from 72% prior to educational intervention to 88% after intervention (p<0.001), and number of "not assessable" images decreased significantly. Percentage agreement between surgeons on the assessments increased from 75% to 87%. The proportion of best possible ratings for fracture reduction and implant position increased from 58% to 72% and from 49% to 66%, respectively. Percentage agreement between surgeons on assessment of reduction and implant position increased.Discussion and ConclusionsA focused educational intervention can improve surgeons' ability to obtain and assess lateral view intraoperative images of the proximal femur and can improve the quality of reduction and implant positioning.



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The impact of antegrade intramedullary nailing start site using the SIGN nail in proximal femoral fractures: A prospective cohort study

Publication date: Available online 16 November 2017
Source:Injury
Author(s): Mohamed Mustafa Diab, Hao-Hua Wu, Edmund Eliezer, Billy Haonga, Saam Morshed, David W. Shearer
IntroductionIn many low and middle-income countries (LMICs) SIGN nail is commonly used for antegrade femoral intramedullary (IM) nailing, using a start site either at the tip of the greater trochanter or piriformis fossa. While a correct start site is considered an essential technical step; few studies have evaluated the impact of using an erroneous start site. This is particularly relevant in settings with limited access to fluoroscopy to aid in creating a nail entry point. The purpose of this study was to evaluate the impact of antegrade SIGN IM nailing start site on radiographic alignment and health-related quality of life.MethodsIn this prospective cohort study, adult patients with proximal femur fractures (OTA 32, subtrochanteric zone) treated with antegrade IM SIGN nail at Muhimbili Orthopaedic Institute (MOI), Dar es Salaam, Tanzania were enrolled. Start site was determined on the immediate postoperative X-ray and was graded on a continuous scale based on distance of the IM nail center from the greater trochanteric tip. The primary outcome measurement was coronal alignment on the post-operative x-ray. The secondary outcomes were reoperation rates, RUST scores and EQ5D scores at one year follow-up.ResultsSeventy-nine patients were enrolled. 50 of them (63.3%) had complete data at 1year and were included in the final data analysis. Of the fifty patients, nine (18%) had IM nails placed laterally, 26 (52%) medially and 15 (30%) directly over the tip of the greater trochanter. Compared to a start site at the tip or medial to the greater trochanter, a lateral start site was 9 times more likely to result in a varus malalignment (95% CI: 1.42–57.70, p=0.021).ConclusionsLateral start site was associated with varus malalignment. Although lateral start site was not significantly associated with reoperation, varus deformity was associated with higher reoperation rates. Surgeons should consider avoiding a start site lateral to the tip of the greater trochanter or allow the nail to rotate to avoid malalignment when using the SIGN nail for proximal femur fractures.



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Trans-articular Kirschner wire fixation in treating complex tibial plateau fractures complicated by multiple ligaments injuries: A case report and literature review

Publication date: Available online 16 November 2017
Source:Injury
Author(s): Jianbin Wu, Yiyang Wang, Feiya Zhou, Lei Yang, Jun Tang
There is no guideline and consensus about when and how to treat accompanying multi-ligaments injuries, especially anterior and/or posterior cruciate ligaments, in tibial plateau fractures. We report one case of fracture and dislocation of tibial plateau, treated by open reduction and internal plates fixation, augmented by trans-articular Kirschner wire fixation to overcome instability and malrotation of the knee joints discovered intraoperatively. The Kirschner wire was removed about four weeks after the index operation, and the patient begun functional exercise from then on. The fracture united uneventfully, the knee joint regained full range of motion without malalignment. The patient reported excellent knee function and satisfied with the operations. We suppose that trans-articular Kirschner wires fixation combined with open reduction internal plates fixation maybe is a treatment solution in treating complex tibial plateau fractures complicated by multiple ligamentous injuries.



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Femoral intertrochanteric nail (fitn): a new short version design with an anterior curvature and a geometric match study using post-operative radiographs

Publication date: Available online 16 November 2017
Source:Injury
Author(s): Shi-Min Chang, Sun-Jun Hu, Zhuo Ma, Shou-Chao Du, Ying-Qi Zhang
ObjectiveFemoral intertrochanteric fractures are usually fixed with short, straight cephalomedullary nails. However, mismatches between the nail and the femur frequently occur, such as tip impingement and tail protrusion. The authors designed a new type of short femoral intertrochanteric nail (fitn) with an anterior curvature (length=19.5cm, r=120cm) and herein report the geometric match study for the first of 50 cases.MethodsA prospective case series of 50 geriatric patients suffering from unstable intertrochanteric fractures (AO/OTA 31 A2/3) were treated. There were 15 males and 35 females, with an average age of 82.3 years. Post-operatively, the nail entry point position in the sagittal greater trochanter (in three categories, anterior, central and posterior), the nail-tip position in the medullary canal (in 5-grade scale) and the nail-tail level to the greater trochanter (in 3-grade scale) were measured using X-ray films.ResultsFor the nail entry point measurement, 5 cases were anterior (10%), 38 cases were central (76%), and 7 cases were posterior (14%). For the distal nail-tip position, 32 cases (64%) were located along the central canal axis, 13 cases (26%) were located anteriorly but did not contact the anterior inner cortex, 2 cases (4%) showed less than one-third anterior cortex thickness contact, and 3 cases (6%) were located posteriorly with no contact. For the proximal nail-tail level, there were no protrusions over the greater trochanter in 15 cases (30%), protrusion of less than 5mm in 29 cases (58%), and protrusion of more than 5mm in 6 cases (12%). The fitness was very high, as 96% cases showed no tip-cortex contact, and 88% cases showed less than 5mm proximal tail protrusion.ConclusionThe newly designed femoral intertrochanteric nail has a good geometric match with the femur medullary canal and the proximal length in the Chinese population.



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Acute Kidney Injury: It's not just the ‘big’ burns

Publication date: Available online 16 November 2017
Source:Injury
Author(s): L.A. Kimmel, S. Wilson, R.G. Walker, Y. Singer, H. Cleland
BackgroundAcute Kidney Injury (AKI) complicates the management of at least 25% of patients with severe burns and is associated with long term complications. Most research focuses on the patients with more severe burns, and whether the same factors are associated with the development of AKI in patients with burns between 10 and 19% total body surface area (TBSA) is unknown. The aims of this study were to examine the incidence of, and factors associated with, the development of AKI in patients with%TBSA≥10, as well as the relationship with hospital metrics such as length of stay (LOS).MethodsRetrospective medical record review of consecutive burns patients admitted to XXXX, the major adult burns centre in XXXX, Australia. Demographic and injury details were recorded. Factors associated with AKI were determined using multiple logistic regression.ResultsBetween 2010 and June 2014, 300 patients were admitted with burn injury and data on 267 patients was available for analysis. Median age was 54.5 years with 78% being male. Median%TBSA was 15 (IQR 12, 20). The AKI incidence, as measured by the RIFLE criteria, was 22.5%, including 15% (27/184) in patients with%TBSA 10–19. Factors associated with AKI included increasing age and%TBSA (OR 1.05 p<0.001) as well as increased surgeries (p<0.041) and a cardiac comorbidity (p<0.01). All patients with renal comorbidity developed AKI. In the%TBSA 10–19 cohort, only increasing age (OR 1.05 p<0.001) was associated with AKI. After accounting for confounding factors, the probability of discharge from hospital in Non-AKI group was greater than for the AKI patients at all time points (P<0.001).ConclusionThis is the first study to show an association between patients with%TBSA 10–19 and AKI. Given the association between AKI and complications, prospective research is needed to further understand AKI in burns with the aim of risk reduction.



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Is external fixation needed for the treatment of tibial fractures with acute compartment syndrome?

Publication date: Available online 15 November 2017
Source:Injury
Author(s): Tae Hun Kim, Jun Young Chung, Keun Su Kim, Hyung Keun Song
Acute compartment syndrome (ACS) after tibial fracture carries a risk of various complications, including infection, delayed union, nonunion, nerve damage, and poor prognosis. For the treatment of fractures with ACS, fasciotomy is conducted, and the method to stabilise the fracture has to be considered. Thirty-five patients who underwent surgery for ACS with tibial shaft fractures were evaluated, and the results of initial internal fixation (Group I, 20 patients) and initial external fixation (Group II, 15 patients) were analysed. The mean age was 41 years. Five patients needed additional surgery for bone union. Complications occurred in 4 cases, but no deep infection was reported. The time to bone union, the need for additional surgery, and the incidence of complications in Group I and Group II were not statistically different. For the treatment of ACS with tibial fracture, immediate internal fixation and changing from external fixation to internal fixation did not affect the clinical course.



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Diabetes and Healing Outcomes in Lower Extremity Fractures: A Systematic Review

Publication date: Available online 15 November 2017
Source:Injury
Author(s): Hilary Gortler, Jessyca Rusyn, Charles Godbout, Jas Chahal, Emil H. Schemitsch, Aaron Nauth
ObjectiveThe purpose of this study was to review the rates of adverse healing outcomes following surgical fixation of lower extremity fractures in diabetic patients and matched controls.Materials and MethodsSearches of PubMed, MEDLINE, CINAHL and Embase were performed for studies published between the date of database inception and July 6, 2015. Patient characteristics and the incidence of adverse healing outcomes (nonunion, malunion, delayed union, infection and reoperation) were extracted from each study. The occurrence of each fracture healing complication was pooled and analyzed for comparisons between diabetic and non-diabetic patients. An odds ratio with a 95% confidence interval for each healing outcome was calculated between the diabetic and non-diabetic groups.ResultsDiabetes was found to significantly increase rates of malunion, infection and reoperation in patients with surgically treated lower extremity fractures. In addition, when only peripheral lower extremity fractures (i.e. below the knee) were examined, diabetes significantly increased the rates of nonunion.ConclusionDiabetes substantially alters bone metabolism and soft tissue healing, posing a risk of adverse fracture healing and other complications. This systematic review provides evidence that the presence of diabetes significantly increases the risks of infection, malunion, nonunion and re-operation across a wide variety of surgically treated lower extremity fractures. This study provides prognostic information for clinicians and may aid in guiding treatment for this population.



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Stromal Vascular Fraction-enriched Fat Grafting for the Treatment of Symptomatic End-neuromata

The purpose of the study is to illustrate the technical procedure of stromal vascular fraction (SVF)-enriched fat grafting as a novel treatment of symptomatic end-neuromata. This technique provides advantages of both the mechanical barrier and the biological action at the cellular level by the processed and concentrated SVF.

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Influence of enhanced recovery after surgery programs on laparoscopy-assisted gastrectomy for gastric cancer: a systematic review and meta-analysis of randomized control trials

Abstract

Background

This meta-analysis is aimed to evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) programs in gastric cancer patients undergoing laparoscopy-assisted gastrectomy (LAG).

Methods

We performed a meta-analysis of randomized control trials involving either enhanced recovery after surgery (ERAS)/fast track surgery (FTS) for patients underwent LAG. EMBASE, Pubmed, Web of science, and Cochrane Library were searched. Primary outcomes included the length of postoperative hospital stay, cost of hospitalization, postoperative complications, and readmission rate.

Results

Five randomized control trials were eligible for analysis. There were 159 cases in FTS group and 156 cases in conventional care group. Compared with conventional care group, FTS group relates to shorter postoperative hospital stay (WMD − 2.16; 95% CI − 3.05 to − 1.26, P < 0.00001), less cost of hospitalization (WMD − 4.72; 95% CI − 6.88 to − 2.55, P < 0.00001), shorter time to first flatus (WMD − 9.72; 95% CI − 13.75 to − 5.81, P < 0.00001), lower level of C-reaction protein on postoperative days 3 or 4 (WMD − 19.66; 95% CI − 28.98 to − 10.34, P < 0.00001), higher level of albumin on postoperative day 4 (WMD 3.45; 95% CI 2.01 to 4.89, P < 0.00001), and postoperative day 7 (WMD 5.63; 95% CI 1.01 to 10.24, P = 0.02). Regarding postoperative complications, no significant differences were observed between FTS group and conventional care group (OR 0.63, 95% CI 0.37 to 1.09, P = 0.10). The readmission rate of FTS group was comparable to conventional care group (WMD 3.14; 95% CI 0.12 to 81.35, P = 0.49).

Conclusions

Among patients undergoing LAG, FTS is associated with shorter postoperative hospital stay, rapid postoperative recovery, and decreased cost without increasing complications or readmission rate. The combined effects of the two methods could further accelerate clinical recovery of gastric cancer patients.



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52 Loop-mediated isothermal amplification PCR (LAMP) for the rapid identification of invasive meningococcal disease in the emergency department

Background

Despite successful vaccination programmes meningococcal disease (MD) remains the leading infectious cause of septicaemia and death in children in the UK and Ireland.1,2 The early diagnosis of MD significantly improves outcomes with reduced morbidity and mortality.1,2 The early stages of MD are often indistinguishable from a simple viral illness making an early positive diagnosis of MD difficult.1 Hibergene have developed a commercially available bedside Loop-mediated isothermal AMPlification PCR (LAMP-MD) test that is a highly sensitive 0.89 (95%CI 0.72–0.96) and specific 1.0 (95%CI 0.97–1.0) for identifying children with invasive MD (4) (figure 1).

Figure 1

Aims

The aims of this RCEM funded study were:

Assess the ease of use and suitability for the ED

Determine the time taken to perform the test

Independently verify LAMP-MD performance against TaqMan quantitative PCR.

Method

The LAMP-MD was assessed for practicality and ease of use within the ED including an assessment of training needs, footprint and health and safety requirements.

For verification of the Hibergene LAMP-MD analyser and assay we used dry nasopharyngeal swabs sent for viral screening. Additional verification was undertaken using N. meningitidis genomic DNA spiked over a range of concentrations. This included serotypes A, B, C, W, X and Y and a dilution series to determine the limit of detection. All samples were then analysed using real time TaqMan qPCR.

Results

The LAMP-MD analyser was easy to use and could be accommodated in the ED

The mean time for detection of Meningococcal DNA was 14.01 min

Detection of meningococcal serogroups A, B, C, W, X and Z was confirmed

The detection limit for dry nasopharyngeal swabs was below 2 genomic copies per µl

No non-specific amplification was observed in 17 randomly selected negative clinical swabs

The LAMP-MD assay was 100% sensitive and specific relative to real-time TaqMAN PCR.

Conclusion

LAMP-MD is a practical, rapid point of care test that can reliably detect all Meningococcal serotypes in less than 15 min.

Funding has been secured to perform a PERUKI supported study to investigate the potential for LAMP-MD in the diagnosis of meningococcal disease in children.

References

Meningitis Research Foundation. Meningococcal Meningitis and Septicaemia Guidance Notes2014.

Ó Maoldomhnaigh, et al. Invasive meningococcal disease in children in Ireland. PMID: 27566800.

NICE. Management of petechial rash.

Bourke TW, et al. Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children. PMID: 25728843.



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44 Quantifying the 5 year mortality of frequent attenders to the emergency department

Introduction

Frequent Attenders (FA) to Emergency Departments (ED) are a vulnerable population which we perceive to have a high morbidity and mortality. ED clinicians find this population challenging and they are at risk of being stigmatised. There has been little published work in the UK quantifying the risk of death in this population. Here we aim to quantify the 5 year mortality of this population and identify key risk factors.

Methods

We identified a cohort of frequent attenders, defined as attending the ED 5 times or more between 1/4/2010 and 31/3/2011. We followed these patients via their electronic patient record from Cambridge University Hospital which is linked to the NHS spine.

Overall mortality for the population has been calculated and we will produce a censored Kaplan-Meier survival estimate to account for patients we have been unable to follow up. Using a cox regression model we will analyse the impact of the chosen variables (age, sex, continued number of attendances to ED, and presence of a major physical or psychological illness or alcohol abuse) on mortality.

Initial results

(pending full statistical analysis)

5 year mortality for the entire cohort was 24% and when limited to 16–65 year olds 5 year mortality was 11%. There will be a full risk factor analysis of this data available.

Conclusion

Frequent Attenders to Addenbrooke's ED have a risk of death much greater than the normal population. A large proportion of the patients who died were very elderly and so 5 year mortality is less surprising but may suggest a need for further community care involvement to reduce ED attendance.

The crucial finding is that the risk of death for adult FAs between the age of 16–65 is much higher than would be expected of the normal population. This indicates a need to treat this population with increased care.



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Are rising admission thresholds good medicine?

Like many emergency physicians of a certain age, we find ourselves nostalgic for a time when it felt easier to admit patients into the hospital than now. Many of us now find ourselves feeling that we discharge many patients from the ED who we would have admitted years ago. It turns out that this hunch is correct. In an enormous retrospective database study, Steven Wyatt et al1 examined admission thresholds across 47 EDs in England over a 5-year period. They used a simple regression model to adjust for known predictors of admission, including robustly recorded items such as age and sex, and less well recorded items such as diagnosis.

Initially, the conversion rate (the number of admissions divided by the number of attendances) looks similar across the years, but when adjusted for various measures of acuity, there is a 3% reduction in admissions over the 5-year period....



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28 Are we measuring what we think we are measuring? Qualitative research exploring the role of the 0-10 pain score within the adult emergency department

Objectives and background

The assessment of pain in the emergency department (ED) is difficult but important for appropriate management of pain. Guidelines for the management of acute pain in the ED worldwide advocate using numeric rating scales such as the 0–10 pain score as tools to ensure consistency of documenting patient's pain, and this is mandated at initial assessment in many EDs. Studies of interventions to improve pain management in the ED indicate that whilst the inclusion of mandatory pain scoring within interventions may improve documentation of pain, there was mixed evidence as to whether this resulted in improvements in provision of analgesia. As part of a wider study looking at barriers and enablers to pain management in the ED, we explored how pain scoring was used in the ED.

Methods

Qualitative data were collected within 3 case study EDs in the UK. Data comprised 143 hours of non-participant observation, 37 ED staff interviews and 19 patient interviews. Data were analysed using thematic analysis.

Results

Observation showed variation in how the pain score was documented between EDs. Some staff documented the score directly reported by the patient, whilst others documented a score they formulated using a combination of physiological signs, behavioural signs and presence of a 'known' painful condition. ED staff appeared to understand the score as an absolute measure used to guide analgesia requirements or triage categories rather than a relative measure used to document changes in pain levels. Even when documenting patient reported scores, they perceived patient reported scores to be inconsistent with their own assessment of the patients pain level, particularly where this could lead to patients being managed under a higher triage category or receiving stronger analgesia than ED staff considered appropriate. Staff documented pain scores that were appropriate for the treatment they planned to provide, rather than the scores reported by the patient, in particular when the pain score was used as a tool for auditing appropriate pain management.

Conclusions

The pain score appeared to have parallel but misaligned roles: to assess patient pain and ED staff practice. ED staff faced conflict between the need to record pain to ensure accountability of pain management, and recording pain to reflect the patient's report. The role of the pain score needs to be reviewed in order for pain scoring to improve the patient experience of pain management in the ED.



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Changes in admission thresholds in English emergency departments

Background

The most common route to a hospital bed in an emergency is via an Emergency Department (ED). Many recent initiatives and interventions have the objective of reducing the number of unnecessary emergency admissions. We aimed to assess whether ED admission thresholds had changed over time taking account of the casemix of patients arriving at ED.

Methods

We conducted a retrospective cross-sectional analysis of more than 20 million attendances at 47 consultant-led EDs in England between April 2010 and March 2015. We used mixed-effects logistic regression to estimate the odds of a patient being admitted to hospital and the impact of a range of potential explanatory variables. Models were developed and validated for four attendance subgroups: ambulance-conveyed children, walk-in children, ambulance-conveyed adults and walk-in adults.

Results

23.8% of attendances were for children aged under 18 years, 49.7% were female and 30.0% were conveyed by ambulance. The number of ED attendances increased by 1.8% per annum between April 2010–March 2011 (year 1) and April 2014–March 2015 (year 5). The proportion of these attendances that were admitted to hospital changed negligiblybetween year 1 (27.0%) and year 5 (27.5%). However, after adjusting for patient and attendance characteristics, the odds of admission over the 5-year period had reduced by 15.2% (95% CI 13.4% to 17.0%) for ambulance-conveyed children, 22.6% (95% CI 21.7% to 23.5%) for walk-in children, 20.9% (95% CI 20.4% to 21.5%) for ambulance conveyed adults and 22.9% (95% CI 22.4% to 23.5%) for walk-in adults.

Conclusions

The casemix-adjusted odds of admission via ED to NHS hospitals in England have decreased since April 2010. EDs are admitting a similar proportion of patients to hospital despite increases in the complexity and acuity of presenting patients. Without these threshold changes, the number of emergency admissions would have been 11.9% higher than was the case in year 5.



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20 Risk factors for admission at three, urban emergency departments in england: a cross-sectional analysis of attendances over one month

Objective

To investigate factors associated with unscheduled admission following presentation to Emergency Departments (EDs) at three hospitals in England.

Design and setting

Cross-sectional analysis of attendance data for patients from three urban EDs in England: a large teaching hospital and major trauma centre (Site 1), and two district general hospitals (Sites 2 and 3). Variables included: patient age, gender, ethnicity, deprivation score, arrival date and time, arrival by ambulance or otherwise, a variety of ED workload measures, inpatient bed occupancy rates and admission outcome. Coding inconsistencies in routine ED data used for this study meant that diagnosis could not be included.

Outcome measure

The primary outcome for the study was unscheduled admission.

Participants

All adults aged 16 and over attending the three inner London EDs in December 2013. Data on 19 734 unique patient attendances were gathered.

Results

Outcome data were available for 19 721 attendances (>99%), of whom 6263 (32%) were admitted to hospital. Site 1 was set as the baseline site for analysis of admission risk. Risk of admission was significantly greater at Sites 2 and 3 (AOR relative to Site 1 for Site 2 was 1.89, 95% CI:1.74 to 2.05, p<0.001), and for patients of black or black British ethnicity (1.29, 1.16–1.44, p<0.001). Deprivation was strongly associated with admission. Analysis of departmental and hospital-wide workload pressures gave conflicting results, but proximity to the 'four-hour target' (a rule that limits patient stays in EDs to four hours in the NHS in England) emerged as a strong driver for admission in this analysis (3.61, 3.30–3.95, p<0.001).

Conclusion

This study found statistically significant variations in odds of admission between hospital sites when adjusting for various patient demographic and presentation factors, suggesting important variations in ED- and clinician-level behaviour relating to admission decisions. The four-hour target is a strong driver for emergency admission.



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Evaluating an admission avoidance pathway for children in the emergency department: outpatient intravenous antibiotics for moderate/severe cellulitis

Objective

Children with moderate/severe cellulitis requiring intravenous antibiotics are usually admitted to hospital. Admission avoidance is attractive but there are few data in children. We implemented a new pathway for children to be treated with intravenous antibiotics at home and aimed to describe the characteristics of patients treated on this pathway and in hospital and to evaluate the outcomes.

Methods

This is a prospective, observational cohort study of children aged 6 months–18 years attending the ED with uncomplicated moderate/severe cellulitis in March 2014–January 2015. Patients received either intravenous ceftriaxone at home or intravenous flucloxacillin in hospital based on physician discretion. Primary outcome was treatment failure defined as antibiotic change within 48 hours due to inadequate clinical improvement or serious adverse events. Secondary outcomes include duration of intravenous antibiotics and complications.

Results

115 children were included: 47 (41%) in the home group and 68 (59%) in the hospital group (59 hospital-only, 9 transferred home during treatment). The groups had similar clinical features. 2/47 (4%) of the children in the home group compared with 8/59 (14%) in the hospital group had treatment failure (P=0.10). Duration of intravenous antibiotics (median 1.9 vs 1.8 days, P=0.31) and complications (6% vs 10%, P=0.49) were no different between groups. Home treatment costs less, averaging $A1166 (£705) per episode compared with $A2594 (£1570) in hospital.

Conclusions

Children with uncomplicated cellulitis may be able to avoid hospital admission via a home intravenous pathway. This approach has the potential to provide cost and other benefits of home treatment.



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36 Frailty flying squad: an emergency department focussed acute care of the elderly service DR genevieve robson, royal united hospital NHS foundation trust

Introduction

The over 75 s make up 20% of our ED attendances. The greatest increase has been in the over 85 s. This very elderly cohort are more likely to be frail and are 10X more likely to require admission than 20–40 year olds and once in hospital have longer stays. There is evidence that multidisciplinary care and early Comprehensive Geriatric Assessment (CGA) improves outcomes for older patients, reducing readmissions, long term care, greater satisfaction and lower costs. The aim of this project was to improve the acute care provided to our older patients at the Front Door of the hospital.

Methodology

3 month pilot project underpinned by Big Room Quality Improvement methodology. The Frailty Big Room meets weekly and includes input from clinicians, QI experts and a data analyst. This project was driven by the following aims:

Frailty Flying Squad to see as many older±frail patients referred for admission as close to the front door as possible.

CGA at the front door with discharge planning from first review

MDT approach

Expedited discharge or transfer to other services from ED.

Review following day to make sure management plans being followed through or discharge without ward teams having to become involved.

Frailty Flying Squad Team:

2 Medical Nurse Practitioners

Physiotherapist

Consultant geriatrician

Key Performance Indicators:

Length of Stay

Readmission within 30 days of initial review

Results

355 patients were seen. 168 (47%) of patients were over 85 and the median Rockwood frailty score for the whole cohort was 6. 209 patients were ED referrals and 85 were GP referrals for admission. 237 (67%) patients were seen in ED, 49 in MAU and 7 in ED obs. During the pilot period, 97 patients who had been referred for admission were discharged direct from ED. 56 (16%) of patients had zero length of stay. A low number (9.4%) of patients were readmitted within 30 days.

Figure 1

LOS

Figure 2

Length of stay for the > 85s 2016 and 2017 compared

Conclusion

A multidisciplinary Acute Care of the Elderly Team predominantly based in the Emergency department can provide effective early Comprehensive Geriatric Assessment; facilitating discharge home from the Emergency Department, reducing length of stay for those admitted and reducing readmission rates within 30 days.



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Predicting outcomes in traumatic out-of-hospital cardiac arrest: the relevance of Utstein factors

Background

Given low survival rates in cases of traumatic out-of-hospital cardiac arrest (OHCA), there is a need to identify factors associated with outcomes. We aimed to investigate Utstein factors associated with achieving return of spontaneous circulation (ROSC) and survival to hospital in traumatic OHCA.

Methods

The Victorian Ambulance Cardiac Arrest Registry (VACAR) was used to identify cases of traumatic OHCA that received attempted resuscitation and occurred between July 2008 and June 2014. We excluded cases aged <16 years or with a mechanism of hanging or drowning.

Results

Of the 660 traumatic OHCA patients who received attempted resuscitation, ROSC was achieved in 159 patients (24%) and 95 patients (14%) survived to hospital (ROSC on hospital handover). Factors that were positively associated with achieving ROSC in multivariable logistic regression models were age ≥65 years (adjusted OR (AOR)=1.56, 95% CI: 1.01 to 2.43) and arresting rhythm (shockable (AOR=3.65, 95% CI: 1.64 to 8.11) and pulseless electrical activity (AOR=2.15, 95% CI: 1.36 to 3.39) relative to asystole). Similarly, factors positively associated with survival to hospital were arresting rhythm (shockable (AOR=3.92, 95% CI: 1.64 to 9.41) relative to asystole), and the mechanism of injury (falls (AOR=2.16, 95% CI: 1.03 to 4.54) relative to motor vehicle collisions), while trauma type (penetrating (AOR=0.27, 95% CI: 0.08 to 0.91) relative to blunt trauma) and event region (rural (AOR=0.39, 95% CI: 0.19 to 0.80) relative to urban) were negatively associated with survival to hospital.

Conclusions

Few patient and arrest characteristics were associated with outcomes in traumatic OHCA. These findings suggest there is a need to incorporate additional information into cardiac arrest registries to assist prognostication and the development of novel interventions in these trauma patients.



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Fewer REBOA complications with smaller devices and partial occlusion: evidence from a multicentre registry in Japan

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) performed by emergency physicians has been gaining acceptance as a less invasive technique than resuscitative thoracotomy.

Objective

To evaluate access-related complications and duration of occlusions during REBOA.

Methods

Patients with haemorrhagic shock requiring REBOA, from 18 hospitals in Japan, included in the DIRECT-IABO Registry were studied. REBOA-related characteristics were compared between non-survivors and survivors at 24 hours. 24-Hour survivors were categorised into groups with small (≤8 Fr), large (≥9 Fr) or unusual sheaths (oversized or multiple) to assess the relationship between the sheath size and complications. Haemodynamic response, occlusion duration and outcomes were compared between groups with partial and complete REBOA.

Results

Between August 2011 and December 2015, 142 adults undergoing REBOA were analysed. REBOA procedures were predominantly (94%) performed by emergency medicine (EM) physicians. The median duration of the small sheath (n=53) was 19 hours compared with 7.5 hours for the larger sheaths (P=0.025). Smaller sheaths were more likely to be removed using external manual compression (96% vs 45%, P<0.001). One case of a common femoral artery thrombus (large group) and two cases of amputation (unusual group) were identified. Partial REBOA was carried out in more cases (n=78) and resulted in a better haemodynamic response than complete REBOA (improvement in haemodynamics, 92% vs 70%, P=0.004; achievement of stability, 78% vs 51%, P=0.007) and allowed longer occlusion duration (median 58 vs 33 min, P=0.041). No statistically significant difference in 24-hour or 30-day survival was found between partial and complete REBOA.

Conclusion

In Japan, EM physicians undertake the majority of REBOA procedures. Smaller sheaths appear to have fewer complications despite relatively prolonged placement and require external compression on removal. Although REBOA is a rarely performed procedure, partial REBOA, which may extend the occlusion duration without a reduction in survival, is used more commonly in Japan.



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24 An audit into the number of patients suffering out-of-hospital cardiac arrest that are resuscitated despite a high likelihood of futility

Background

For a significant number of patients suffering out-of-hospital cardiac arrest (OHCA) cardiopulmonary resuscitation (CPR) is likely to be futile and attempting it may be the wrong thing to do. Anticipatory care plans with do-not-attempt cardiopulmonary resuscitation (DNACPR) instructions exist to prevent this. Anecdotally we felt that many patients present to our Emergency Department (ED) with ongoing resuscitation which was not in their best interests. The aim of this study was to establish the proportion of patients arriving in our ED with ongoing CPR who had low, intermediate or high risk of futility.

Methods

The survival outcome and past medical history of patients with OHCA brought into the ED of the Royal Infirmary of Edinburgh in 2015 were extracted from hospital records. Indicators of general deteriorating health and clinical indicators of underlying life limiting conditions were used to populate the Supportive and Palliative Care Tool (SPICT). The SPICT score was used as a measure of likely CPR futility. A SPICT score of 0–2 meant low risk of futility, 3–4 intermediate risk and >5 a high risk.

Results

Of the 283 cases, 202 (71.4%) had a low risk of CPR futility; 46 (16.3%) an intermediate risk; and 35 (12.4%) were considered to be at high risk of CPR futility. In all low, intermediate and high risk categories, the commonest outcome was to be pronounced dead in A and E (55.4%, 73.9% and 71.4% respectively). For the low risk of futility group, a significant proportion (27.7%) survived to hospital discharge, whereas patients in the intermediate and high risk groups rarely survived with only 2.17% and 2.86% respectively discharged from hospital. Of the low, intermediate and high risk patients, 11.4%, 91.3% and 100% respectively had one or more significant underlying comorbidities.

Conclusions

Our results suggest that community DNACPR implementation in Edinburgh is suboptimal, with many patients resuscitated and transported to the ED with ongoing resuscitation despite a high likelihood of futility. It is unclear what is required to improve this situation. Possible avenues for improvement may be more anticipatory care planning in the community, better recording of the outcomes of key conversations with patients and carers, or more consistent implementation of these plans by Ambulance Service responders. We plan further work to establish how this system can be changed to serve patients and their families better.



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Risk factors and outcomes associated with post-traumatic headache after mild traumatic brain injury

Objectives

To determine the prevalence and potential risk factors of acute and chronic post-traumatic headache (PTH) in patients with mild to moderate traumatic brain injury (TBI) in a prospective longitudinal observational multicentre study. Acute PTH (aPTH) is defined by new or worsening of pre-existing headache occurring within 7 days after trauma, whereas chronic PTH (cPTH) is defined as persisting aPTH >3 months after trauma. An additional goal was to study the impact of aPTH and cPTH in terms of return to work (RTW), anxiety and depression.

Methods

This was a prospective observational study conducted between January 2013 and February 2014 in three trauma centres in the Netherlands. Patients aged 16 years and older with a GCS score of 9–15 on admission to the ED, with loss of consciousness and/or amnesia were prospectively enrolled. Follow-up questionnaires were completed at 2 weeks and 3 months after injury with the Head Injury Symptom Checklist, the Hospital Anxiety and Depression Scale and RTW scale.

Results

In total, 628 patients were enrolled in the study, 469 completed the 2-week questionnaire (75%) at 2 weeks and 409 (65%) at 3 months. At 2 weeks, 238 (51%) had developed aPTH and at 3 months 95 (23%) had developed cPTH. Female gender, younger age, headache immediately at the ED and CT scan abnormalities increased the risk for aPTH. Risk factors for cPTH were female gender and headache at the ED. Patients with cPTH were less likely to have returned to work than those without cPTH (35% vs 14%, P=0.001). Patients with aPTH and cPTH more often report anxiety (20% and 28%, P=0.001) and depression (19% and 28%, P=0.001) after trauma in comparison with the group without PTH (10% anxiety and 8% depression).

Conclusions

PTH is an important health problem with a significant impact on long-term outcome of TBI patients. Several risk factors were identified, which can aid in early identification of subjects at risk for PTH.



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32 Do low-risk patients with non-cardiac chest pain prefer early discharge after rapid rule-out in the emergency department?

Background

There has been a recent drive to implement rapid rule-out strategies which allow the early discharge of low-risk patients with suspected cardiac chest pain directly from the Emergency Department (ED). Previously, such patients would have been admitted to a hospital bed for observation and delayed biomarker testing. While the drive to implement rapid rule-out strategies comes from healthcare providers, there has been little assessment of patient perspectives on early discharge, in what is known to be a high-anxiety presentation. We aimed to explore patient perspectives on the acceptability of early discharge strategies.

Methods

This prospective quantitative survey was conducted on consecutive patients admitted from the ED to a short-stay ward for evaluation of suspected cardiac chest pain at a single centre in the UK. All patients were discharged within 36 hours with a diagnosis of low-risk chest pain. The written questionnaire was designed with closed answer questions with responses standardised along a 5-point Likert scale and was completed by patients upon discharge. Ethical approval was obtained.

Results

Of 739 patients requested to complete the survey, 278 (37.6%) responded. Mean age 56.6 years (SD 13.4), 263/278 (94.6%) White British, mean length of stay 15.5 hours (SD 6.6), 6/278 (2.2%) had a major adverse event (MACE) at 30 days. Responders were more likely to be female than non-responders (49.6% vs 37.5%, p=0.001), otherwise groups were matched in age, cardiac risk factors, length of stay and the presence of MACE (p>0.05 for all).

Table 1

Summary of patients' responses from questionnaire

The majority of patients, 197/278 (70.8%) would have been satisfied or very satisfied with early discharge directly from the ED, with 36/278 (13.0%) expressing dissatisfaction with a proposed rapid rule-out strategy. However, 249/277 (89.9%) of responders were reassured by admission to the ward and 112/273 (41.0%) felt they could not have spent any less time in hospital. Through binary logistic regression we analysed potential predictors of dissatisfaction with early discharge, these were sex, age, severity and type of pain at presentation, previous ischaemic heart disease, family history and found none were significant.

Conclusions

Most patients would be satisfied with a rapid rule-out strategy, however, it should be acknowledged that patients receive reassurance from hospital admission and over 10% of patients would be dissatisfied with discharge direct from ED. Improved patient information and shared decision making is required when rapid discharge strategies are incorporated into practice.



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Emergency versus standard response: time efficacy of Londons Air Ambulance rapid response vehicle

Objective

The potential increased risk of an emergency response using a rapid response vehicle (RRV) should only be accepted when it allows a clinically significant time saving for management of patients who are critically injured or sick. Air ambulance services often use an RRV to maintain operational resilience. We compared the RRV response time on emergency versus standard driving to inform emergency services of time efficacy of emergency response in an urban environment.

Methods

Prospective observational controlled study of response data of emergency and standard driving. An identical RRV shadowed the medical team until the team was dispatched to a job (emergency driving). The shadow RRV then drove to the same given location from the same origin location in equal traffic conditions being compliant with all traffic signals, road signs and speed limits (standard driving).

Results

The emergency response resulted in an estimated reduction in median response time of 14 min (95% CI 9 to 19) which represented a time saving of 54.9%. The estimated difference in distance travelled (0.6 km) was not statistically significant. Median speed was significantly higher when using an emergency response (46.1 IQR 39–53.4 km/hour) versus standard response (20.1 IQR 16.3–24.7 km/hour), with an estimated difference of –24.5 km/hour (95% CI –28.8 to –20.5).

Conclusions

The current study found RRVs to be significantly quicker when responding with lights, sirens and traffic rule exemptions compared with a response being compliant with all traffic signals, road signs and speed limits.



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40 ED crowding: the acceptability of dysfunction

Background

Crowding in the Emergency Department is internationally recognised as one of the greatest challenges to healthcare provision. Numerous studies have highlighted the ill-effects of crowding, including increased length of stay, mortality and cost per admission. Crowding is typically a manifestation of a hospital at full capacity and its main contributor is the practice of boarding patients in the ED. Therefore, a functioning flow system is advised to ease the burden. Different predictive tools/algorithms assess the degree of crowding. The National Emergency Department Overcrowding Scale (NEDOCS) is used effectively in other countries but has not been validated in Ireland.

Aims

To assess crowding in a major Irish teaching hospital over a three week period at regular time periods using the NEDOCS.

To look at the time from decision to admit to ward bed availability in order to improve flow through the department.

Staffs perception of crowding was assessed at a random single time point.

Methods

Application of the NEDOCS score in the Emergency Department along with the use of internal Patient Administration System (PAS) to track patient movement through the ED.

Results

During the three week period, the NEDOCS score was frequently at level 6 (dangerously overcrowded) or level 5 (severely overcrowded) (see figure 1). Emergency patient registrations peaked between 1000 hours to 1300 hours whereas the peak admission time to wards was between 1900 hours and 2300 hours. At a random time point, Universal staff perception of crowding in the department was perceived as 'It's a nice day'. However the NEDOCS level was 4 (overcrowded) suggesting significant crowding.

Figure 1

Figure 2

Average reception activity per 24 hour

Conclusion

Our Hospital is operating at a consistent level of crowding that can negatively impact on patients. Access to inpatient beds is available late in the day, creating a time lag between decision to admit and transfer to ward. Staff perception did not correlate with NEDOCs score, possibly reflecting a conditioning and acceptance of staff to crowding.

Discussion

We plan to validate the NEDOCS score in an Irish Emergency Department. Crowding is a significant issue in the Irish Healthcare setting. The '40% of inpatient beds by 11 am' needs to be adopted by our hospital. Our study suggests that our emergency staff accept the dysfunctional as the norm.



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