bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial)
Authors: Biagioni Emanuela , Tosi Martina , Berlot Giorgio , Castiglione Giacomo , Corona Alberto , De Cristofaro Maria Giovanna , Donati Abele , Feltracco Paolo , Forfori Francesco , Fragranza Fiorentino , Murino Patrizia , Piazza Ornella , Tullo Livio , Grasselli Giacomo , D"Amico Roberto , Girardis Massimo 
Published: February 2021

IntroductionIn patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose.Methods and analysisThe study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days.Ethics and disseminationThe study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell’Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences.Trial registration detailsThe trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.
Gut microbiota composition and arterial stiffness measured by pulse wave velocity: case–control study protocol (MIVAS study)
Authors: Salvado Rita , Santos-Minguez Sandra , Agudo-Conde Cristina , Lugones-Sanchez Cristina , Cabo-Laso Angela , Mª Hernandez-Sanchez Jesus , Benito Rocio , Rodriguez-Sanchez Emiliano , Gomez-Marcos Manuel A , Hernandez-Rivas Jesus M , Guimarães Cunha Pedro , Garcia-Ortiz Luis , Investigators MIVAS 
Published: February 2021

IntroductionIntestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness.Methods and analysisAn observational case—control study will be developed. Cases will be defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), Cardio-Ankle Vascular Index (CAVI), brachial ankle pulse wave velocity (ba or ba-PWV) above the 90thpercentile, for age and sex, of the reference population. Controls will be selected from the same population as cases. The study will be developed in Primary Healthcare Centres. We will select 500 subjects (250 cases and 250 controls), between 45 and 74 years of age. Cases will be selected from a database that combines data from EVA study (Spain) and Guimarães/Vizela study (Portugal). Measurements: cf-PWV will be measured using the SphygmoCor system, CAVI, ba-PWV and Ankle-Brachial Index will be determined using VaSera device. Gut microbiome composition in faecal samples will be determined by 16S ribosomal RNA sequencing. Lifestyle will be assessed by food frequency questionnaire, adherence to the Mediterranean diet and IPAQ (International Physical Activity Questionnaire). Body composition will be evaluated by bioimpedance.Ethics and disseminationThe study has been approved by ‘Committee of ethics of research with medicines of the health area of Salamanca’ on 14 December 2018 (cod. 2018-11-136) and the ’Ethics committee for health of Guimaraes’ (Portugal) on 15 October 2019 (ref: 67/2019). All study participants will sign an informed consent form agreeing to participate in the study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow a better description of gut microbiota in patients with arterial stiffness.Trial registration detailsClinicalTrials.gov, identifierNCT03900338
Implementation of patient-reported outcome measures and patient-reported experience measures in melanoma clinical quality registries: a systematic review
Authors: Blood Zachary , Tran Anh , Caleo Lauren , Saw Robyn , Dieng Mbathio , Shackleton Mark , Soyer H Peter , Arnold Chris , Mann Graham J , Morton Rachael L 
Published: February 2021

ObjectivesTo identify patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) in clinical quality registries, for people with cutaneous melanoma, to inform a new Australian Melanoma Clinical Outcomes Registry; and describe opportunities and challenges of routine PROM/PREM collection, especially in primary care.DesignSystematic review.Primary and secondary outcome measuresWhich PROMs and PREMs are used in clinical quality registries for people with cutaneous melanoma, how they are collected, frequency of collection, participant recruitment methods and funding models for each registry.Results1134 studies were identified from MEDLINE, PreMEDLINE, Embase, PsychInfo, Cochrane Database of Abstracts of Reviews of Effects databases and TUFTS Cost-Effectiveness Analysis Registry, alongside grey literature, from database inception to 5th February 2020. Following screening, 14 studies were included, identifying four relevant registries: Dutch Melanoma Registry, Adelphi Real-World Disease-Specific Programme (Melanoma), Patient-Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship Registry, and Cancer Experience Registry. These used seven PROMs: EuroQol-5 Dimensions, Functional Assessment of Cancer-General (FACT-G) and FACT-Melanoma (FACT-M), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer 30 (EORTC QLQ-C30), Fatigue Assessment Scale Hospital Anxiety and Depression Scale, Patient-Reported Outcome Measures Information System-29 and one PREM; EORTC QLQ-Information Module 26. PROMs/PREMs in registries were reported to improve transparency of care; facilitate clinical auditing for quality assessment; enable cost-effectiveness analyses and create large-scale research platforms. Challenges included resource burden for data entry and potential collection bias toward younger, more affluent respondents. Feedback from patients with melanoma highlighted the relevance of PROMs/PREMs in assessing patient outcomes and patient experiences.ConclusionsClinical registries indicate PROMs/PREMs for melanoma care can be incorporated and address important gaps, however cost and collection bias may limit generalisability.PROSPERO registration numberCRD42018086737.
Therapeutic effects of exercise interventions for patients with chronic kidney disease: protocol for an overview of systematic reviews and meta-analyses of clinical trials
Authors: Zhang Fan , Wang Hui , Huang Liuyan , Zhang Huachun 
Published: February 2021

IntroductionAn increasing number of systematic reviews and meta-analyses of clinical trials have begun to investigate the effects of exercise interventions in patients with chronic kidney disease (CKD). To systematically appraise and synthesise these results, we will conduct an overview of systematic reviews and meta-analyses.Methods and analysisThis is a protocol for an overview of systematic reviews and meta-analyses. We will search four databases: PubMed, Embase, Web of Science Core Collection and Cochrane Central Registry of Controlled Trials. Systematic reviews and meta-analyses of clinical trials evaluating the effect of exercise interventions on patients with CKD will be included. Two independent authors will screen titles and abstracts retrieved in the literature search and select studies meeting the eligibility criteria for full-text review. The methodological quality of the included reviews will be assessed using A Measurement Tool to Assess Systematic Reviews-2. We estimate the summary effects for each meta-analyses based on the standardised mean difference and its 95% CI. Additionally, the heterogeneity will be assessed by I2 evidence of small-study effect and the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation system.Ethics and disseminationEthics approval are not required as no private information from individuals is collected. The results will be published in a peer-reviewed journal or disseminated in relevant conferences.PROSPERO registration numberCRD42020223591.
Initiatives for improving delayed discharge from a hospital setting: a scoping review
Authors: Cadel Lauren , Guilcher Sara J T , Kokorelias Kristina Marie , Sutherland Jason , Glasby Jon , Kiran Tara , Kuluski Kerry 
Published: February 2021

ObjectiveThe overarching objective of the scoping review was to examine peer reviewed and grey literature for best practices that have been developed, implemented and/or evaluated for delayed discharge involving a hospital setting. Two specific objectives were to review what the delayed discharge initiatives entailed and identify gaps in the literature in order to inform future work.DesignScoping review.MethodsElectronic databases and websites of government and healthcare organisations were searched for eligible articles. Articles were required to include an initiative that focused on delayed discharge, involve a hospital setting and be published between 1 January 2004 and 16 August 2019. Data were extracted using Microsoft Excel. Following extraction, a policy framework by Doern and Phidd was adapted to organise the included initiatives into categories: (1) information sharing; (2) tools and guidelines; (3) practice changes; (4) infrastructure and finance and (5) other.ResultsSixty-six articles were included in this review. The majority of initiatives were categorised as practice change (n=36), followed by information sharing (n=19) and tools and guidelines (n=19). Numerous initiatives incorporated multiple categories. The majority of initiatives were implemented by multidisciplinary teams and resulted in improved outcomes such as reduced length of stay and discharge delays. However, the experiences of patients and families were rarely reported. Included initiatives also lacked important contextual information, which is essential for replicating best practices and scaling up.ConclusionsThis scoping review identified a number of initiatives that have been implemented to target delayed discharges. While the majority of initiatives resulted in positive outcomes, delayed discharges remain an international problem. There are significant gaps and limitations in evidence and thus, future work is warranted to develop solutions that have a sustainable impact.
Current management of moderate to severe traumatic pneumothoraces: a survey of emergency clinicians
Authors: Avery Pascale , Watkins Millie , Benger Jonathan , Carlton Edward 
Published: February 2021

BackgroundTraumatic pneumothoraces are present in one-fifth of multiple trauma victims. Traditional teaching mandates the insertion of a chest drain in the majority of cases. However, recent observational evidence suggests a trend towards conservative management. The aim of this survey was to understand current emergency medicine (EM) practice in placing chest drains for the management of moderate to severe traumatic pneumothoraces.MethodologyThe survey was developed through expert consensus and sent electronically to senior EM doctors in 21 sites internationally. It described six clinical/imaging vignettes asking ‘how likely are you to insert an intercostal chest drain to manage the pneumothorax in ED?’. A five-point response was available fromvery unlikelytovery likely. All pneumothoraces were >1 cm on imaging, but mechanism, physiology and need for ventilation varied.ResultsOf a potential 606 respondents, 222 responses were received (37% response rate). Respondents were from five different countries, with the majority qualified for more than 10 years (median; 18 years). Within each scenario, there was a large variation in responses with the exception of tension pneumothorax. For vignettes without tension pneumothorax, there was a range from 52% (non-compromised 1 cm pneumothorax in a ventilated patient) to 89% (open pneumothorax with minimal clinical compromise) in respondents reporting that they would belikelyorvery likelyto insert a chest drain.ConclusionThere is considerable variation in clinical practice involving both conservative and invasive strategies in the treatment of moderate to severe traumatic pneumothoraces. This suggests clinical equipoise for interventional trials to determine the optimal management strategy for this patient group.
Surgical decision making in premenopausal BRCA carriers considering risk-reducing early salpingectomy or salpingo-oophorectomy: a qualitative study
Authors: Gaba Faiza , Goyal Shivam , Marks Dalya , Chandrasekaran Dhivya , Evans Olivia , Robbani Sadiyah , Tyson Charlotte , Legood Rosa , Saridogan Ertan , McCluggage W Glenn , Hanson Helen , Singh Naveena , Evans D Gareth , Menon Usha , Manchanda Ranjit 
Published: February 2021

BackgroundAcceptance of the role of the fallopian tube in ‘ovarian’ carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among BRCA carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360).MethodsIn-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached. Wording and sequencing of questions were left open with probes used to elicit additional information. All interviews were audio-recorded, transcribed verbatim, transcripts analysed using an inductive theoretical framework and data managed using NVIVO-v12.ResultsInformational saturation was reached following 24 interviews. Seven interconnected themes integral to surgical decision making were identified: fertility/menopause/cancer risk reduction/surgical choices/surgical complications/sequence of ovarian-and-breast prophylactic surgeries/support/satisfaction. Women for whom maximising ovarian cancer risk reduction was relatively more important than early menopause/quality-of-life preferred RRSO, whereas those more concerned about detrimental impact of menopause chose RRESDO. Women managed in specialist familial cancer clinic settings compared with non-specialist settings felt they received better quality care, improved hormone replacement therapy access and were more satisfied.ConclusionMultiple contextual factors (medical, physical, psychological, social) influence timing of risk-reducing surgeries. RRESDO offers women delaying/declining premenopausal oophorectomy, particularly those concerned about menopausal effects, a degree of ovarian cancer risk reduction while avoiding early menopause. Care of high-risk women should be centralised to centres with specialist familial gynaecological cancer risk management services to provide a better-quality, streamlined, holistic multidisciplinary approach.
Carotid artery stenting in a patient with an anomalous vertebral artery origin from the external carotid artery
Authors: Beer-Furlan André , Munich Stephan A 
Published: February 2021

The existence of carotid basilar anastomoses has been well documented embryologically, anatomically, and, in the case of the persistent trigeminal and hypoglossal arteries, angiographically. Conversely, anomalous origins of the vertebral arteries (VA) are not very common with an incidence ranging from 3% to 8%. Multiple variations of the VA origin have been reported in the literature, including arising from the aortic arch, from the common, internal, or external carotid arteries and subclavian branches.1 There are only four cases reported in the literature of VA origin from the external carotid artery.2–5 We report the fifth case in which the anomalous origin was identified during the investigation of an acute ischemic stroke. Video 1 emphasizes the importance of anatomical knowledge prior to endovascular or surgical interventions. It also highlights technical nuances of carotid artery stenting in a patient with anomalous VA origin from the external carotid artery.Video 1
Book review
Authors: Metcalf Michael 
Published: February 2021

Computing was in a state of crisis. As the price of the hardware continued to fall, and the power of processors continued to rise, the cost of programming the devices was becoming a major part of the overall cost. Small wonder. In 1954, although there were only a few dozen computers in existence, their programming was carried by a small army of experts coding at worst in binary code and at best in some form of assembler.
Enter John Backus. This somewhat unorthodox but brilliant mathematician had been hired off the street by IBM in 1949 to work on its Selective Sequence Electronic Calculator (SSEC) computer. As a result of his experience there, he realised that the only way out of this impasse was to enable programmers to code more efficiently using a higher level of abstraction. But that would not, itself, be sufficient. It would be essential that the final binary code produced by any automatic coding system be as efficient as that being produced by the laborious hand coding.
Byzantine Fault-tolerant State-machine Replication from a Systems Perspective
Authors: Distler Tobias 
Published: February 2021

Byzantine fault-tolerant (BFT) state-machine replication makes it possible to design systems that are resilient against arbitrary faults, a requirement considered crucial for an increasing number of use cases such as permissioned blockchains, firewalls, and SCADA systems. Unfortunately, the strong fault-tolerance guarantees provided by BFT replication protocols come at the cost of a high complexity, which is why it is inherently difficult to correctly implement BFT systems in practice. This is all the more true with regard to the plethora of solutions and ideas that have been developed in recent years to improve performance, availability, or resource efficiency. This survey aims at facilitating the task of building BFT systems by presenting an overview of state-of-the-art techniques and analyzing their practical implications, for example, with respect to applicability and composability. In particular, this includes problems that arise in the context of concrete implementations, but which are often times passed over in literature. Starting with an in-depth discussion of the most important architectural building blocks of a BFT system (i.e., clients, agreement protocol, execution stage), the survey then focuses on selected approaches and mechanisms addressing specific tasks such as checkpointing and recovery.
Distribution and Risk Factors of Water-Related Accidents for General Aviation Aircraft
Authors: Yang Ruiliang , LibinYang  , Zhao Lina , Geng Donghan 
Published: February 2021

In the past two decades, dozens to more than a hundred people have died each year in water-related accidents, most of which general aviation has accounted for. To identify the distribution and risk factors of fatal water-related accidents for general aviation aircraft, a total of 594 water-related accidents according to 14 CFR Part 91 from 2009 to 2019 were chosen from the National Transportation Safety Board’s online database. A two-step approach, consisting of a univariable logistic regression and a multivariable logistic regression, was performed to estimate the effects of 28 parameters. Results show that aircraft with a rated power of more than 100 horsepower (

odds

ratio
>
5

), instrument conditions (

odds

ratio
=
25.585

), flying night operations (

odds

ratio
=
3.717

), and cruise phase (

odds

ratio
=
11.699

) possessed an elevated risk for a fatal outcome. This research is the first to identify the distribution and risk factors of fatal water-related accidents under 14 CFR Part 91. The necessity and importance of survival equipment for water-related accidents are also highlighted in this paper.
The miR–181a–SFRP4 Axis Regulates Wnt Activation to Drive Stemness and Platinum Resistance in Ovarian Cancer
Authors: Belur Nagaraj Anil , Knarr Matthew , Sekhar Sreeja , Connor R. Shae , Joseph Peronne , Kovalenko Olga , Fleming Alexis , Surti Arshia , Nurmemmedov Elmar , Beltrame Luca , Marchini Sergio , Kahn Michael , DiFeo Analisa 
Published: February 2021

Abstract

Wnt signaling is a major driver of stemness and chemoresistance in ovarian cancer, yet the genetic drivers that stimulate its expression remain largely unknown. Unlike other cancers, mutations in the Wnt pathway are not reported in high-grade serous ovarian cancer (HGSOC). Hence, a key challenge that must be addressed to develop effective targeted therapies is to identify nonmutational drivers of Wnt activation. Using an miRNA sensor-based approach, we have identified miR-181a as a novel driver of Wnt/β-catenin signaling. miR-181ahigh primary HGSOC cells exhibited increased Wnt/β-catenin signaling, which was associated with increased stem-cell frequency and platinum resistance. Consistent with these findings, inhibition of β-catenin decreased stem-like properties in miR-181ahigh cell populations and downregulated miR-181a. The Wnt inhibitor SFRP4 was identified as a novel target of miR-181a. Overall, our results demonstrate that miR-181a is a nonmutational activator of Wnt signaling that drives stemness and chemoresistance in HGSOC, suggesting that the miR–181a–SFRP4 axis can be evaluated as a novel biomarker for β-catenin–targeted therapy in this disease.

Significance:
These results demonstrate that miR-181a is an activator of Wnt signaling that drives stemness and chemoresistance in HGSOC and may be targeted therapeutically in recurrent disease.