bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of clinical outcomes between intermittent and continuous monitoring of central venous oxygen saturation (ScvO2) in patients with severe sepsis and septic shock: a pilot study
Authors: Huh Jin Won , Oh Bum Jin , Lim Chae-Man , Hong Sang-Bum , Koh Younsuck 
Published: November 2012

BackgroundThe Surviving Sepsis Campaign (SSC) to improve patient outcomes in severe sepsis and septic shock contains recommendations for protocolised resuscitation including early goal-directed therapy (EGDT) resuscitation. In EGDT, central venous oxygen saturation (ScvO2) is measured as the target monitoring value. The objective of this study was to determine whether intermittent measurement of ScvO2is as clinically effective as continuous monitoring in EGDT implementation.MethodsThis prospective, observational, pilot study was performed at an emergency room and general ward in ASAN Medical Centre, a 2680-bed teaching hospital. One hundred and six patients with severe sepsis or septic shock were enrolled and assigned to an intermittent monitoring group (n=53) or continuous monitoring group (n=53).ResultsWithin 6 h of the EGDT, interventions by the treating physicians were assessed, including intravenous fluid administration, use of vasopressors and compliance with SSC bundles. After 6 h of the EGDT, 41.5% of all goals (primary outcome) were achieved in the intermittent group and 35.8% in the continuous group (p=0.550). Intensive Care Unit (ICU) mortality, hospital mortality and length of ICU stay did not differ between groups.ConclusionsDuring EGDT, intermittent ScvO2monitoring was not inferior to continuous ScvO2monitoring when delivered within the first 6 h of intervention.
Patients’ and ambulance service clinicians’ experiences of prehospital care for acute myocardial infarction and stroke: a qualitative study
Authors: Togher Fiona Jayne , Davy Zowie , Siriwardena Aloysius Niroshan 
Published: November 2012

BackgroundPatients with suspected acute myocardial infarction (AMI) and stroke commonly present first to the ambulance service. Little is known about experiences of prehospital care which are important for measuring the quality of services for patients with AMI or stroke.AimWe explored experiences of patients, who had accessed the ambulance service for AMI or stroke, and clinicians regularly treating patients for these conditions in the prehospital setting.MethodA qualitative research design was employed to obtain rich and detailed data to explore and compare participants’ experiences of emergency prehospital care for AMI and stroke.ResultsWe conducted 33 semistructured interviews with service users and clinicians and one focus group with five clinicians. Four main themes emerged: communication, professionalism, treatment of condition and the transition from home to hospital. Patients focused on both personal and technical skills. Technical knowledge and relational skills together contributed to a perception of professionalism in ambulance personnel. Patients’ experience was enhanced when physical, emotional and social needs were attended to and they emphasised effective communication within the clinician–patient relationship to be the key. However, we found a discrepancy between paramedics’ perceptions of patients’ expectations and patients’ lack of knowledge of the paramedic role.ConclusionsFactors that contribute to better patient experience are not necessarily understood in the same way by patients and clinicians. Our findings can contribute to the development of patient experience measures for prehospital care.
Identifying older people at high risk of future falls: development and validation of a screening tool for use in emergency departments
Authors: Tiedemann Anne , Sherrington Catherine , Orr Teresa , Hallen Jamie , Lewis Donna , Kelly Ann , Vogler Constance , Lord Stephen R , Close Jacqueline C T 
Published: November 2012

BackgroundHospital emergency departments (EDs) treat a high proportion of older people, many as a direct consequence of falling.ObjectiveTo develop and externally validate a fall risk screening tool for use in hospital EDs and to compare the tool's predictive ability to existing screening tools.MethodsThis prospective cohort study involved two hospital EDs in Sydney, Australia. Potential participants were people aged 70+ years who presented to the ED after falling or with a history of 2+ falls in the previous year and were subsequently discharged. 219 people participated in the tool development study and 178 people participated in the external validation study. Study measures included number of fallers during the 6-month follow-up period, and physical status, medical history, fall history and community service use.Results31% and 35% of participants fell in the development and external validation samples, respectively. The developed two-item screening tool included: 2+ falls in the past year (OR 4.18, 95% CI 2.61 to 6.68) and taking 6+ medications (OR 1.89, CI 1.18 to 3.04). The area under the receiver operating characteristic curve (AUC) was 0.70 (0.64–0.76). This represents significantly better predictive ability than the measure of 2+ previous falls alone (AUC 0.67, 0.62–0.72, p=0.02) and similar predictive ability to the FROP-Com (AUC 0.73, 0.67–0.79, p=0.25) and PROFET screens (AUC 0.70, 0.62–0.78, p=0.5).ConclusionsA simple, two-item screening tool demonstrated good external validity and accurately discriminated between fallers and non-fallers. This tool could identify high risk individuals who may benefit from onward referral or intervention after ED discharge.
Effect of paralytic type on time to post-intubation sedative use in the emergency department
Authors: Watt John M , Amini Albert , Traylor Brittany R , Amini Richard , Sakles John C , Patanwala Asad E 
Published: November 2012

ObjectiveTo determine the difference between rocuronium and succinylcholine with regard to post-intubation sedative initiation in the emergency department.MethdsThis was a retrospective cohort study conducted in a tertiary care emergency department (ED) in the USA. Consecutive adult patients intubated in the ED using succinylcholine or rocuronium for paralysis were included. Data collected included patient demographics, vital signs, medications used post-intubation and times of drug administration. Patients were divided into two groups based on the type of paralytic used for rapid sequence intubation: (1) rocuronium or (2) succinylcholine. All patients received etomidate for induction of sedation. Time between intubation and post-intubation sedative use was compared between the two groups using an unpaired Student's t test.Main resultsA total of 200 patients were included in the final analyses (100 patients in each group). There were no significant differences between the groups with regard to patient demographics, vital signs or other baseline characteristics. After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). The remaining patients received sedation as bolus doses only. Mean time between intubation and post-intubation sedative use was significantly greater in the rocuronium group compared with the succinylcholine group (27 min vs 15 min, respectively; p<0.001).ConclusionsPatients intubated with rocuronium had greater delays in post-intubation sedative initiation compared with succinylcholine.
FoxM1 and Wnt/β-Catenin Signaling in Glioma Stem Cells
Authors: Gong Aihua , Huang Suyun 
Published: November 2012

Abstract
Cancer stem cells may be responsible for tumor initiation and maintenance. The molecular mechanisms that control cancer stem cells are related to alterations in various signaling pathways, including the Wnt/β-catenin signaling pathway. The canonical Wnt/β-catenin signaling pathway is one of the major signaling systems in stem and progenitor cells, and aberrant activation of the Wnt/β-catenin signaling pathway is common in human cancers. As with β-catenin, FoxM1 has been found to play important roles in a number of cancers. In this review, we discuss the evidence that FoxM1 affects the expression and function of a variety of genes that are critical to the survival, proliferation, invasion, angiogenesis, and self-renewal of cancer stem cells. We highlight the pivotal roles of the Wnt/β-catenin and FoxM1 signaling pathways in neural stem and progenitor cells and glioma stem cells. We also discuss the evidence for cross-talk between the β-catenin and FoxM1 signaling pathways in the regulation of the stemness and tumorigenicity of glioma stem cells. Cancer Res; 72(22); 5658–62. ©2012 AACR.
Realizing the Clinical Potential of Cancer Nanotechnology by Minimizing Toxicologic and Targeted Delivery Concerns
Authors: Singh Sanjay , Sharma Arati , Robertson Gavin P. 
Published: November 2012

Abstract
Nanotechnology has the potential to make smart drugs that would be capable of targeting cancer but not normal cells and to load combinations of cooperating agents into a single nanosized particle to more effectively treat this disease. However, to realize the full potential of this technology, the negative aspects associated with these nanoparticles need to be overcome. This review discusses concerns in the field limiting realization of the full clinical potential of this technology, which are toxicity and targeted delivery. Strategies to overcome these hurdles are also reviewed, which could lead to attainment of the full clinical potential of this exciting technology. Cancer Res; 72(22); 5663–8. ©2012 AACR.
Cell Surface Receptor FPR2 Promotes Antitumor Host Defense by Limiting M2 Polarization of Macrophages
Authors: Liu Ying , Chen Keqiang , Wang Chunyan , Gong Wanghua , Yoshimura Teizo , Liu Mingyong , Wang Ji Ming 
Published: November 2012

Abstract
FPR2 (Fpr2 in mouse) is a G-protein–coupled receptor interacting with bacterial and host-derived chemotactic agonists. Fpr2 supports innate and adaptive immune responses as illustrated by the reduction in severity of allergic airway inflammation in Fpr2-KO mice, due to impaired trafficking of antigen-presenting dendritic cells (DC). The aim of this study is to examine the role of Fpr2 in host antitumor responses. We found that Fpr2-KO mice bearing subcutaneously implanted Lewis lung carcinoma (LLC) cells exhibited significantly shortened survival than normal mice due to more rapidly growing tumors. In contrast, in Fpr2-transgenic mice overexpressing Fpr2, subcutaneously implanted LLC tumors grew more slowly than those in wild-type (WT) littermates. Investigation of tumor tissues revealed an increased number of macrophages associated with tumors grown in Fpr2-KO mice. Macrophages derived from Fpr2-KO mice showed a more potent chemotactic response to LLC-derived supernatant (LLC Sup), which could be neutralized by an anti-CCL2 antibody. The increased chemotaxis of Fpr2-KO mouse macrophages in response to LLC Sup was due to their higher level expression of CCR4, a chemokine receptor that also recognizes the ligand CCL2. Furthermore, macrophages from Fpr2-KO mice acquired an M2 phenotype after stimulation with LLC Sup. These results suggest that Fpr2 plays an important role in host defense against implanted LLC by sustaining macrophages in an M1 phenotype with more potent antitumor activities. Cancer Res; 73(2); 550–60. ©2012 AACR.
SMAD2,SMAD3andSMAD4Mutations in Colorectal Cancer
Authors: Fleming Nicholas I. , Jorissen Robert N. , Mouradov Dmitri , Christie Michael , Sakthianandeswaren Anuratha , Palmieri Michelle , Day Fiona , Li Shan , Tsui Cary , Lipton Lara , Desai Jayesh , Jones Ian T. , McLaughlin Stephen , Ward Robyn L. , Hawkins Nicholas J. , Ruszkiewicz Andrew R. , Moore James , Zhu Hong-Jian , Mariadason John M. , Burgess Antony W. , Busam Dana , Zhao Qi , Strausberg Robert L. , Gibbs Peter , Sieber Oliver M. 
Published: November 2012

AbstractActivation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis. Mutation spectra were compared between the genes, the pathogenicity of mutations was assessed, and relationships with clinicopathologic features were examined. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively. A significant overrepresentation of two genetic hits was detected for SMAD4 and SMAD3, consistent with these genes acting as tumor suppressors. SMAD4 mutations were associated with mucinous histology. The mutation spectra of SMAD2 and SMAD3 were highly similar to that of SMAD4, both in mutation type and location within the encoded proteins. In silico analyses suggested the majority of the mutations were pathogenic, with most missense changes predicted to reduce protein stability or hinder SMAD complex formation. The latter altered interface residues or disrupted the phosphorylation-regulated Ser-Ser-X-Ser motifs within SMAD2 and SMAD3. Functional analyses of selected mutations showed reductions in SMAD3 transcriptional activity and SMAD2–SMAD4 complex formation. Joint biallelic hits in SMAD2 and SMAD3 were overrepresented and mutually exclusive to SMAD4 mutation, underlining the critical roles of these three proteins within the TGF-β signaling pathway. Cancer Res; 73(2); 725–35. ©2012 AACR.
Unfavourable cardiovascular disease risk profiles in a cohort of Dutch and British haemophilia patients
Authors: Fischer Kathelijn , Makris Michael , Tait Campbell R. , Chowdary Pratima , Collins Peter W. , Meijer Karina , Roosendaal Goris , Schutgens Roger E. G. , Mauser-Bunschoten Eveline P. , Fransen van de Putte Dietje E. 
Published: November 2012

SummaryCardiovascular disease (CVD) mortality is reported to be decreased in haemophilia patients, but reports on the prevalence of CVD risk factors are conflicting. A cross-sectional assessment of CVD risk profiles was performed in a large cohort of haemophilia patients. Baseline data on CVD risk factors of 709 Dutch and UK haemophilia patients aged ≥ 30 years were analysed and compared with the general age-matched male population. CVD risk profiles were assessed using the QRISK®2–2011 and SCORE algorithms. Although QRISK®2 was only validated in the UK, comparison with SCORE indicated similar properties of QRISK®2 in both Dutch and UK patients (correlation 0.86). Mean age was 49.8 years. Hypertension was more common in haemophilia patients than in the general population (49% vs. 40%), while the prevalences of obesity and hypercholesterolaemia were lower (15 vs. 20% and 44 vs. 68%, respectively), and those of diabetes and smoking were similar. The predicted 10-year QRISK®2 risk was significantly higher in haemophilia patients than in the general population (8.9 vs. 6.7%), indicating more unfavourable cardiovascular disease risk profiles. This increased risk became apparent after the age of 40 years. Our results indicate an increased prevalence of hypertension and overall more unfavourable CVD risk profiles in haemophilia patients compared with the general age-matched male population.
Circulating and platelet-derived microparticles in human blood enhance thrombosis on atherosclerotic plaques
Authors: Suades Rosa , Padró Teresa , Vilahur Gemma , Badimon Lina 
Published: November 2012

SummaryPlaque rupture followed by thrombosis is the underlying cause of the majority of acute coronary syndromes. Circulating microparticles (cMPs), membrane blebs released into blood by activated cells, have been associated to vascular diseases. Specifically, high levels of platelet-derived microparticles (pMPs) have been found in patients with coronary disease. However, it is unknown whether microparticles have a contributing role to the development of damaged vessel wall-induced arterial thrombi. The aim of this proof of concept study was to investigate whether an increased number of cMPs and pMPs could functionally contribute to blood thrombogenicity on areas of arterial damage. Microparticles were isolated from blood of healthy volunteers and were characterised by flow cytometry. Effects of microparticles on platelet deposition were assessed under controlled flow conditions exposing damaged arterial wall in the Badimon perfusion chamber and collagen type-I in the flat perfusion chamber to human blood. Platelet deposition on damaged arteries was significantly increased in cMP- and pMP-enriched bloods (p<0.05). pMPs also induced increase in platelet (p<0.05) and fibrin (p<0.05) deposition on human atherosclerotic arteries and in platelet adhesion to purified collagen surfaces. pMP-enriched blood induced a dose-dependent shortening of epinephrine/collagen closure time evaluated by PFA-100 (p<0.001), increased lowdose ADP-induced platelet aggregation by LTA (p<0.05), and decreased clotting time by thromboelastography (p<0.01). In conclusion, an increased content of cMPs and pMPs, even in normal blood conditions, enhance platelet deposition and thrombus formation. This study shows for the first time that, beyond biomarkers of cell activation, blood microparticles have functional effects on cardiovascular atherothrombotic disease.
The use of weighted and scored risk assessment models for venous thromboembolism
Authors: McGinn Thomas , Khorana Alok , Spyropoulos Alex 
Published: November 2012

SummaryFormalised risk assessment models (RAMs) for venous thromboembolism (VTE) using weighted and scored variables have only recently been widely incorporated into international antithrombotic guidelines.Scored and weighted VTE RAMs have advantages over a simplified group-specific VTE risk approach, with the potential to allow more tailored strategies for thromboprophylaxis and an improved estimation of the risk/benefit profile for a particular patient. The derivation of VTE RAMs should be based on variables that are a priori defined or identified in a univariate analysis and the predictive capability of each variable should be rigorously assessed for both clinical and statistical significance and internal consistency and completeness. The assessment of the RAM should include the goodness of fit of the model and construction of a prognostic index score. Any VTE RAM which has been derived must undergo validation of that model before it can be used in clinical practice. Validation of the model should be performed in a “deliberate”prospective fashion across several diverse clinical sites using pre-defined criteria using basic standards for performing model validation. We discuss the basic concepts in the derivation of recent scored and weighted VTE RAMs in hospitalised surgical and medical patients and cancer outpatients, the mechanisms for accurate external validation of the models, and implications for their use in clinical practice.
Upregulating Reverse Cholesterol Transport With Cholesteryl Ester Transfer Protein Inhibition Requires Combination With the LDL-Lowering Drug Berberine in Dyslipidemic Hamsters
Authors: Briand François , Thieblemont Quentin , Muzotte Elodie , Sulpice Thierry 
Published: November 2012

Objective—
This study aimed to investigate whether cholesteryl ester transfer protein inhibition promotes in vivo reverse cholesterol transport in dyslipidemic hamsters.

Methods and Results—

In vivo reverse cholesterol transport was measured after an intravenous injection of
3
H-cholesteryl-oleate–labeled/oxidized low density lipoprotein particles (
3
H-oxLDL), which are rapidly cleared from plasma by liver-resident macrophages for further
3
H-tracer egress in plasma, high density lipoprotein (HDL), liver, and feces. A first set of hamsters made dyslipidemic with a high-fat and high-fructose diet was treated with vehicle or torcetrapib 30 mg/kg (TOR) over 2 weeks. Compared with vehicle, TOR increased apolipoprotein E–rich HDL levels and significantly increased
3
H-tracer appearance in HDL by 30% over 72 hours after
3
H-oxLDL injection. However, TOR did not change
3
H-tracer recovery in liver and feces, suggesting that uptake and excretion of cholesterol deriving from apolipoprotein E-rich HDL is not stimulated. As apoE is a potent ligand for the LDL receptor, we next evaluated the effects of TOR in combination with the LDL-lowering drug berberine, which upregulates LDL receptor expression in dyslipidemic hamsters. Compared with TOR alone, treatment with TOR+berberine 150 mg/kg resulted in lower apolipoprotein E–rich HDL levels. After
3
H-oxLDL injection, TOR+berberine significantly increased
3
H-tracer appearance in fecal cholesterol by 109%.

Conclusion—
Our data suggest that cholesteryl ester transfer protein inhibition alone does not stimulate reverse cholesterol transport in dyslipidemic hamsters and that additional effects mediated by the LDL-lowering drug berberine are required to upregulate this process.
Skin Autofluorescence as a Measure of Advanced Glycation End Products Deposition Is Elevated in Peripheral Artery Disease
Authors: de Vos Lisanne C. , Noordzij Marjon J. , Mulder Douwe J. , Smit Andries J. , Lutgers Helen L. , Dullaart Robin P.F. , Kamphuisen Pieter W. , Zeebregts Clark J. , Lefrandt Joop D. 
Published: November 2012

Objective—
Evidence for an important role of advanced glycation end products (AGEs) in the development of atherosclerosis and cardiovascular disease beyond diabetes mellitus and renal disease is growing. Skin autofluorescence (SAF) is a validated noninvasive measure of tissue AGEs. We hypothesized that SAF is elevated in peripheral artery disease (PAD).

Methods and Results—

A case–control study was performed in 492 patients with PAD and 164 controls, matched for age (mean 66±10 years) and presence of diabetes mellitus. Cardiovascular risk factors and comorbidity (coronary artery disease, cerebrovascular disease, abdominal aortic aneurysm) were assessed. SAF was measured with the AGE Reader. SAF was higher in patients compared with controls: geometric mean 2.77 (95% confidence interval [CI], 2.71–2.83) versus 2.44 (95% CI, 2.35–2.53) arbitrary units,
P
=0.4×10
−8
. In logistic regression, the adjusted odds ratio for the presence of PAD was 2.47 (95% CI, 1.66–3.69) per 1 unit increase of SAF. PAD patients with cardiovascular comorbidity had a higher SAF compared with those without: geometric mean 2.93 (95% CI, 2.85–3.02) versus 2.63 (95% CI, 2.55–2.71) arbitrary units,
P
=0.4×10
−6
, also after correction for confounders. Regression analysis showed that age, smoking, diabetes mellitus, chronic kidney disease, and a history of cerebrovascular disease or abdominal aortic aneurysm were independently associated with SAF in the patients with PAD.

Conclusion—
Accumulation of tissue AGEs is increased in patients with PAD, independent of cardiovascular risk factors and comorbidity, although these conditions are associated with a further increase. These findings underscore the importance of AGEs in PAD, irrespective of the presence of diabetes mellitus and renal insufficiency.