bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation
Authors: Colavecchia A. Carmine , Cohen David A. , Harris Jesse E. , Thomas Jeena M. , Lindberg Scott , Leveque Christopher , Salazar Eric 
Published: September 2017

BACKGROUNDMajor bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization.STUDY DESIGN AND METHODSThis retrospective, single‐institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias.RESULTSDuring this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh‐frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively).CONCLUSIONThe intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation did not reduce intraoperative blood product requirements at a single institution.
The effect of therapeutic leukapheresis on early complications and outcomes in patients with acute leukemia and hyperleukocytosis: a propensity score‐matched study
Authors: Choi Min Hyuk , Choe Yeon Hwa , Park Yongjung , Nah Hyunjin , Kim Sinyoung , Jeong Seok Hoon , Kim Hyun Ok 
Published: September 2017

BACKGROUNDHyperleukocytosis in acute leukemia is associated with higher early mortality due to the major complications of leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulopathy (DIC). Leukapheresis remains an important modality for the management of patients with acute leukemia and hyperleukocytosis. However, the role of leukapheresis in early mortality is controversial. This study sought to evaluate the prognostic impact of leukapheresis and its beneficial effects on TLS and DIC.STUDY DESIGN AND METHODSWe conducted a propensity score‐matched study of 166 patients with acute leukemia and hyperleukocytosis admitted between 2006 and 2016. The incidence of TLS and DIC was determined using well‐defined Cairo‐Bishop criteria for TLS and International Society of Thrombosis and Haemostasis criteria for DIC.RESULTSBefore matching, 27 of 91 patients (30%) with acute myeloid leukemia (AML) and 32 of 75 patients (43%) with acute lymphoblastic leukemia (ALL) underwent leukapheresis. Propensity score matching was performed to adjust for clinical disparities between the leukapheresis and without‐leukapheresis groups and resulted in 22 matched pairs of patients with AML and 16 matched pairs of patients with ALL. After matching, we observed no significant difference in early mortality rates or in the incidence of TLS or DIC between the two groups of patients with AML and ALL.CONCLUSIONAlthough leukapheresis may rapidly reduce white blood cell counts and leukemic blasts, any positive influence of leukapheresis could not be demonstrated by an effect on survival outcome and the incidence of early complications, such as TLS and DIC. These results suggest that a routinely performed, prophylactic leukapheresis cannot be recommended.
Retrospective evaluation of 155 adult equids and 21 foals with tetanus in Western, Northern, and Central Europe (2000–2014). Part 1: Description of history and clinical evolution
Authors: van Galen Gaby , Saegerman Claude , Rijckaert Joke , Amory Helene , Armengou Lara , Bezdekova Barbora , Durie Inge , Findshøj Delany Rikke , Fouché Nathalie , Haley Laura , Hewetson Michael , van den Hoven Rene , Kendall Anna , Malalana Fernando , Muller Cavalleri Jessika , Picavet Tresemiek , Roscher Katja , Verwilghen Denis , Wehrli Eser Meret , Westermann Cornélie , Mair Tim 
Published: September 2017

AbstractObjectiveTo describe clinical data of hospitalized adult equids and foals with tetanus.DesignMulticenter retrospective study (2000–2014).SettingTwenty Western, Northern, and Central European university teaching hospitals and private referral centers.AnimalsOne hundred fifty‐five adult equids (>6 months) and 21 foals (<6 months) with tetanus.InterventionsNone.Measurements and Main ResultsInformation on geographic, annual and seasonal data, demographic‐ and management‐related data, clinical history, clinical examination and blood analysis on admission, complications, treatments, and outcomes were described and statistically compared between adults and foals. The described cases were often young horses. In 4 adult horses, tetanus developed despite appropriate vaccination and in 2 foals despite preventive tetanus antitoxin administration at birth. Castration, hoof abscesses, and wounds were the most common entry sites for adults; umbilical cord infections and wounds for foals. Stiffness was the commonest observed initial clinical sign. Blood analyses frequently revealed an inflammatory response, hemoconcentration, muscle damage, azotemia, negative energy balance, liver damage, and electrolyte and acid base disturbances. Common complications or clinical signs developing during hospitalization included dysphagia, dyspnea, recumbency, hyperthermia, seizures, hyperlipemia, gastrointestinal impactions, dysuria, and laryngeal spasms. Cases were supported with wound debridement, antimicrobial treatment, tetanus antitoxin, muscle spasm and seizure control, analgesia, anti‐inflammatory drugs, fluid therapy, and nutritional support. Mortality rates were 68.4% in adult horses and 66.7% in foals. Foals differed from adult horses with respect to months of occurrence, signalment, management‐related data, potential causative events, clinical signs on admission, blood analysis, complications, and severity grades.ConclusionsThis is the first study that rigorously describes a large population of equids affected by tetanus. The information provided is potentially useful to clinicians for early recognition and case management of tetanus in adult horses and foals. Tetanus affects multiple organ systems, requiring broad supportive and intensive care. Neonatal and adult tetanus in the horse should be considered as distinct syndromes, as in human medicine.
Evaluation of a New Immunochromatography Technology Test (LDBio Diagnostics) To Detect Toxoplasma IgG and IgM: Comparison with the Routine Architect Technique
Authors: Mahinc Caroline , Flori Pierre , Delaunay Edouard , Guillerme Cécile , Charaoui Sana , Raberin Hélène , Hafid Jamal , L'Ollivier Coralie 
Published: September 2017

ABSTRACT

A study comparing the ICT (immunochromatography technology)
Toxoplasma
IgG and IgM rapid diagnostic test (LDBio Diagnostics, France) with a fully automated system, Architect, was performed on samples from university hospitals of Marseille and Saint-Etienne. A total of 767 prospective sera and 235 selected sera were collected. The panels were selected to test various IgG and IgM parameters. The reference technique,
Toxoplasma
IgGII Western blot analysis (LDBio Diagnostics), was used to confirm the IgG results, and commercial kits Platelia Toxo IgM (Bio-Rad) and Toxo-ISAgA (bioMérieux) were used in Saint-Etienne and Marseille, respectively, as the IgM reference techniques. Sensitivity and specificity of the ICT and the Architect IgG assays were compared using a prospective panel. Sensitivity was 100% for the ICT test and 92.1% for Architect (cutoff at 1.6 IU/ml). The low-IgG-titer serum results confirmed that ICT sensitivity was superior to that of Architect. Specificity was 98.7% (ICT) and 99.8% (Architect IgG). The ICT test is also useful for detecting IgM without IgG and is both sensitive (100%) and specific (100%), as it can distinguish nonspecific IgM from specific
Toxoplasma
IgM. In comparison, IgM sensitivity and specificity on Architect are 96.1% and 99.6%, respectively (cutoff at 0.5 arbitrary units [AU]/ml). To conclude, this new test overcomes the limitations of automated screening techniques, which are not sensitive enough for IgG and lack specificity for IgM (rare IgM false-positive cases).
The Exonuclease Activity of Herpes Simplex Virus 1 UL12 Is Required for Production of Viral DNA That Can Be Packaged To Produce Infectious Virus
Authors: Grady Lorry M. , Szczepaniak Renata , Murelli Ryan P. , Masaoka Takeshi , Le Grice Stuart F. J. , Wright Dennis L. , Weller Sandra K. 
Published: September 2017

ABSTRACT

The herpes simplex virus (HSV) type I alkaline nuclease, UL12, has 5′-to-3′ exonuclease activity and shares homology with nucleases from other members of the
Herpesviridae
family. We previously reported that a UL12-null virus exhibits a severe defect in viral growth. To determine whether the growth defect was a result of loss of nuclease activity or another function of UL12, we introduced an exonuclease-inactivating mutation into the viral genome. The recombinant virus, UL12 D340E (the D340E mutant), behaved identically to the null virus (AN-1) in virus yield experiments, exhibiting a 4-log decrease in the production of infectious virus. Furthermore, both viruses were severely defective in cell-to-cell spread and produced fewer DNA-containing capsids and more empty capsids than wild-type virus. In addition, DNA packaged by the viral mutants was aberrant, as determined by infectivity assays and pulsed-field gel electrophoresis. We conclude that UL12 exonuclease activity is essential for the production of viral DNA that can be packaged to produce infectious virus. This conclusion was bolstered by experiments showing that a series of natural and synthetic α-hydroxytropolones recently reported to inhibit HSV replication also inhibit the nuclease activity of UL12. Taken together, our results demonstrate that the exonuclease activity of UL12 is essential for the production of infectious virus and may be considered a target for development of antiviral agents.

IMPORTANCE
Herpes simplex virus is a major pathogen, and although nucleoside analogs such as acyclovir are highly effective in controlling HSV-1 or -2 infections in immunocompetent individuals, their use in immunocompromised patients is complicated by the development of resistance. Identification of additional proteins essential for viral replication is necessary to develop improved therapies. In this communication, we confirm that the exonuclease activity of UL12 is essential for viral replication through the analysis of a nuclease-deficient viral mutant. We demonstrate that the exonuclease activity of UL12 is essential for the production of viral progeny and thus provides an attractive, druggable enzymatic target.
Genome-Wide Mutagenesis of Dengue Virus Reveals Plasticity of the NS1 Protein and Enables Generation of Infectious Tagged Reporter Viruses
Authors: Eyre Nicholas S. , Johnson Stephen M. , Eltahla Auda A. , Aloi Maria , Aloia Amanda L. , McDevitt Christopher A. , Bull Rowena A. , Beard Michael R. 
Published: September 2017

ABSTRACT

Dengue virus (DENV) is a major global pathogen that causes significant morbidity and mortality in tropical and subtropical areas worldwide. An improved understanding of the regions within the DENV genome and its encoded proteins that are required for the virus replication cycle will expedite the development of urgently required therapeutics and vaccines. We subjected an infectious DENV genome to unbiased insertional mutagenesis and used next-generation sequencing to identify sites that tolerate 15-nucleotide insertions during the virus replication cycle in hepatic cell culture. This revealed that the regions within capsid, NS1, and the 3′ untranslated region were the most tolerant of insertions. In contrast, prM- and NS2A-encoding regions were largely intolerant of insertions. Notably, the multifunctional NS1 protein readily tolerated insertions in regions within the
Wing
,
connector
, and β-
ladder
domains with minimal effects on viral RNA replication and infectious virus production. Using this information, we generated infectious reporter viruses, including a variant encoding the APEX2 electron microscopy tag in NS1 that uniquely enabled high-resolution imaging of its localization to the surface and interior of viral replication vesicles. In addition, we generated a tagged virus bearing an mScarlet fluorescent protein insertion in NS1 that, despite an impact on fitness, enabled live cell imaging of NS1 localization and traffic in infected cells. Overall, this genome-wide profile of DENV genome flexibility may be further dissected and exploited in reporter virus generation and antiviral strategies.

IMPORTANCE
Regions of genetic flexibility in viral genomes can be exploited in the generation of reporter virus tools and should arguably be avoided in antiviral drug and vaccine design. Here, we subjected the DENV genome to high-throughput insertional mutagenesis to identify regions of genetic flexibility and enable tagged reporter virus generation. In particular, the viral NS1 protein displayed remarkable tolerance of small insertions. This genetic flexibility enabled generation of several novel NS1-tagged reporter viruses, including an APEX2-tagged virus that we used in high-resolution imaging of NS1 localization in infected cells by electron microscopy. For the first time, this analysis revealed the localization of NS1 within viral replication factories known as “vesicle packets” (VPs), in addition to its acknowledged localization to the luminal surface of these VPs. Together, this genetic profile of DENV may be further refined and exploited in the identification of antiviral targets and the generation of reporter virus tools.
Mii-vitaliSe: a pilot randomised controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis
Authors: Thomas Sarah , Fazakarley Louise , Thomas Peter W , Collyer Sarah , Brenton Sarah , Perring Steve , Scott Rebecca , Thomas Fern , Thomas Charlotte , Jones Kelly , Hickson Jo , Hillier Charles 
Published: September 2017

ObjectivesWhile the health and well-being benefits of physical activity are recognised, people with multiple sclerosis (MS) often face greater barriers than the general population. The Nintendo Wii potentially offers a fun, convenient way of overcoming some of these. The aim was to test the feasibility of conducting a definitive trial of the effectiveness and cost-effectiveness of Mii-vitaliSe; a home-based, physiotherapist-supported Nintendo Wii intervention.DesignA single-centre wait-list randomised controlled study.SettingMS service in secondary care.ParticipantsAmbulatory, relatively inactive people with clinically confirmed MS.InterventionThirty participants were randomised to receive Mii-vitaliSe either immediately (for 12 months) or after a 6-month wait (for 6 months). Mii-vitaliSe consisted of two supervised Nintendo Wii familiarisation sessions in the hospital followed by home use (Wii Sports, Sports Resort and Fit Plus software) with physiotherapist support and personalised resources.OutcomesIncluded self-reported physical activity levels, quality of life, mood, self-efficacy, fatigue and assessments of balance, gait, mobility and hand dexterity at baseline, 6 and 12 months. Interviews (n=25) explored participants’ experiences and, at study end, the two Mii-vitaliSe facilitators’ experiences of intervention delivery (main qualitative findings reported separately).ResultsMean (SD) age was 49.3 (8.7) years, 90% female, with 47% diagnosed with MS <6 years ago and 60% new to active gaming. The recruitment rate was 31% (95% CI 20% to 44%). Outcome data were available for 29 (97%) at 6 months and 28 (93%) at 12 months. No serious adverse events were reported during the study. Qualitative data indicated that Mii-vitaliSe was well-received. Mean Wii use across both groups over the initial 6-month intervention period was twice a week for 27 min/day. Mean cost of delivering Mii-vitaliSe was £684 per person.DiscussionMii-vitaliSe appears acceptable and a future trial feasible and warranted. These findings will inform its design.Trial registrationISRCTN49286846
Man with leg rash
Authors: Hwang Michael Huynh , Khesbak Ziyad , Liu Yiju Teresa 
Published: September 2017

Clinical introductionA 51-year-old male presented to the ED with a rash to his left thigh (figure 1) with erythema, swelling and pain. He endorsed paraesthesias, pruritus, fevers, vomiting and diarrhoea. Initial vitals were unremarkable. He was well appearing with an 8×8 cm violaceous patch on his left medial thigh with vesicles, surrounding erythema and induration with a second, smaller lesion on the right thigh. Both rashes were extremely tender.Figure 1Erythematosus and vesicular rash in bilateral legs.A bedside ultrasound image of the rash was obtained (figure 2).Figure 2Bedside ultrasound of rash.QuestionWhat is the most likely cause of the patient’s rash?A. Herpes zosterB. CellulitisC. Necrotising fasciitisD. Bullous pemphigoid
PP10 Does the use of a post-rosc checklist improve paramedic adherence to local clinical guidance? a mannequin-based pilot randomised controlled study
Authors: Williams David , Clarke Rachel 
Published: September 2017

Aims a BackgroundThe primary aim of this pilot study was to identify whether the use of a checklist could improve paramedic adherence to a clinical guideline during the management of a simulated cardiac arrest patient with the return of spontaneous circulation (ROSC). Increasingly checklists have been shown to reduce mortality and morbidity across a variety of healthcare settings. However there is currently no literature looking at the potential benefits of checklists on UK out-of-hospital cardiac arrest (OOHCA) management.MethodThe study took a convenience sample of nine paramedics from one NHS ambulance service trust. Participants were randomised to one of two groups. Group A, the intervention group, was asked to utilise the checklist on attaining ROSC. Group B, the control group, were asked to manage the ROSC patient in line with standard clinical practice. The results from each participant were recorded on a marking grid, scored out of a possible twenty four points by two individual markers.ResultsFive participants were randomised to group A achieving a median score of twenty three. The other four clinicians were randomised to group B achieving a median score of fourteen. Results were analysed using SPSS software using the Mann-Whitney U test for non-parametric data, producing a p-value of 0.014. This statistical value demonstrates a statistically significant difference within the data.ConclusionThere is a statistically significant difference (p<0.05) between paramedics who utilise and those who do not utilise a checklist for the management of the post-ROSC patient, suggesting that those who do have a greater adherence to clinical guidance. However, the results from this small-scale pilot study cannot imply that the use of a checklist will improve the number of patients that survive to hospital discharge following an OOHCA. Further research is required to identify if there is a clinical significance in using checklists within UK paramedic practice.
PP28 Exploring ‘hear and treat’ practices in three ambulance service trusts
Authors: Bishop-Edwards Lindsey , Knowles Emma , Ahmed Nisar , O’Cathain Alicia 
Published: September 2017

Background‘Hear and treat’ generally refers to the scenario when 999 calls are provided with a response that does not involve dispatch of an ambulance vehicle. Ambulance Quality Indicators available in England show variation across organisations in the amount of ‘hear and treat’ and in the amount of re-contact in 24 hours. However, little is known about variation in the process of ‘hear and treat’. The aim of this qualitative research was to understand more about organisational variation in ‘hear and treat’.MethodsThree ambulance services with deviance from the average amount of ‘hear and treat’ and re-contact in 24 hours were recruited. Non-participant observation was conducted to explore the process involved in both initial call assessment and enhanced clinical assessment. This entailed 40 hours of observation in each organisation (total n=20 call-handlers and 27 clinicians) and semi-structured interviews with call-handlers (n=7), clinicians (n=7) and managers (n=3). A framework approach and NVIVO qualitative data analysis software were used in analysis of the data.FindingsThe findings identified variation around skill mix, role, environment and processes across the three ambulance services that may be factors contributing to variation in the amount of ‘hear and treat’. Commonalties were identified in relation to decision criteria, barriers and frustrations around delivery of appropriate hear and treat responses, for example, patient expectations, communication, information and access to services. Apparent facilitators were also identified, for example, specialist clinicians in mental health.ConclusionsThis research contributes to understanding the nature of ‘hear and treat’ in different ambulance service contexts and the potential reasons for variation in ‘hear and treat’ rates and re-contact rates. This knowledge is important to inform service delivery and management of the increasing demand for urgent and emergency care.