bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digoxin Assays: Frequent, Substantial, and Potentially Dangerous Interference by Spironolactone, Canrenone, and Other Steroids
Authors: Steimer Werner , Müller Christine , Eber Barbara 
Published: January 2020

Abstract
Background: A case of digoxin toxicity resulted from falsely low values with the MEIA II assay for digoxin (AxSYM®; Abbott). The low results were caused by negative interference from canrenone and spironolactone, the latter of which has recently been advocated for the treatment of severe heart failure. Analytical interference from spironolactone has been reported, but little information is available for this effect with newer digoxin assays.
Methods: We examined nine assays (AxSYM, IMx®, TDx®, Emit®, Dimension®, aca®, TinaQuant®, Elecsys®, and Vitros®) for interference by spironolactone, canrenone, and three metabolites. Additionally, all routine digoxin measurements (AxSYM) over a period of 16.5 months (n = 3089) were monitored for interference.
Results: Suppression of the expected values by canrenone (3125 μg/L) was observed for the AxSYM (42% of expected value), IMx (51%), and Dimension (78%) assays. A positive bias was observed for the aca (0.7 μg/L), the TDx (0.62 μg/L), and the Elecsys (&gt;0.58 μg/L). Twenty-five of 669 routinely monitored patients had falsely low results. Nineteen of these had potentially toxic concentrations of digoxin (Emit; &gt;2.0 μg/L), although the AxSYM assay indicated therapeutic or less severe toxic concentrations (Δmax = 7.1 μg/L). Except for two unresolved cases, this was attributable to spironolactone, canrenone, hydrocortisone, or prednisolone. Standard doses of spironolactone (up to 50 mg/day) in patients with heart failure displayed inhibition &lt;11%.
Conclusions: The frequency and magnitude of the false-negative results particularly compromise the use of both microparticle enzyme immunoassays. Not only may toxic concentrations remain unidentified, but intoxication could occur should dosage be increased because of falsely low results. With 11 million digoxin tests/year ordered in the US, conceivably many patients could be adversely affected.
Assessment of the Diagnostic Accuracy of the TDx-FLM II to Predict Fetal Lung Maturity
Authors: Fantz Corinne R , Powell Cynthia , Karon Brad , Parvin Curtis A , Hankins Kelly , Dayal Molina , Sadovsky Yoel , Johari Vandita , Apple Fred S , Gronowski Ann M 
Published: January 2020

Abstract
Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and rapid assessment of markers of fetal lung maturity is critical to clinicians in deciding whether to deliver a preterm infant. Our objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II assay (Abbott Laboratories) for predicting clinically significant RDS.
Methods: Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women were included in the study if they had delivered within 72 h of TDx-FLM II testing and both the mother and infant charts could be reviewed. Women who had been treated with steroids and delivered unaffected infants were excluded from the analysis. The diagnosis of RDS was defined as infants who either were treated with surfactant and/or were placed on a ventilator and/or required continuous positive airway pressure for &gt;1 day.
Results: A total of 185 women met all entry criteria (15 RDS, 170 non-RDS). A cutoff value for a mature result of ≥45 mg/g gave a sensitivity of 100% (95% confidence interval, 82–100%) and a specificity of 90% (95% confidence interval, 78–89%).
Conclusions: The TDx-FLM II appears to predict clinically significant RDS when a cutoff of ≥45 mg/g is used for mature results. Further studies will be required to confirm these findings.
Quantitative Analysis of a MDR1 Transcript for Prediction of Drug Resistance in Acute Leukemia
Authors: Fujimaki Shin-ichi , Funato Tadao , Harigae Hideo , Fujiwara Junko , Kameoka Junichi , Meguro Kuniaki , Kaku Mitsuo , Sasaki Takeshi 
Published: January 2020

Abstract
Background: Assessing the drug resistance of leukemic cells is important for treatment of leukemia. We developed a quantitative reverse transcription (RT)-PCR method for multidrug resistance 1 (MDR1) and multidrug resistance-related protein 1 (MRP1) transcripts to evaluate drug resistance, and applied it to clinical samples.
Methods: The cutoffs for copy numbers of MDR1 and MRP1 transcripts were defined based on copy numbers in healthy bone marrow mononuclear cells. To confirm that the cutoffs reflected biological resistance, we established vincristine (VCR)-resistant K562 sublines that showed various degrees of drug resistance and examined the correlation between the copy numbers of these transcripts and the biological resistance of these clones. In addition, we compared the sensitivity and specificity of quantitative RT-PCR to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric (FCM) analysis.
Results: The defined cutoff for copy numbers of MDR1 transcripts corresponded with the degree of biological resistance of VCR-resistant K562 sublines. Clinical study revealed that the concentrations of MDR1 mRNA in all relapsed patients with acute myelogenous leukemia (AML) were above the cutoff. Moreover, both AML and acute lymphoblastic leukemia patients with high MDR1 mRNA expression at diagnosis tended to show a low remission rate and short remission periods. No association was observed between the amounts of MRP1 transcripts and clinical outcomes. The specificity and sensitivity of quantitative RT-PCR for MDR1 were superior to the MTT assay and FCM analysis.
Conclusion: These results suggest the efficacy of this quantitative analysis of MDR1 transcripts for the prediction of clinical drug resistance in acute leukemia.
Detection of Human Kallikrein 4 in Healthy and Cancerous Prostatic Tissues by Immunofluorometry and Immunohistochemistry
Authors: Obiezu Christina V , Soosaipillai Antoninus , Jung Klaus , Stephan Carsten , Scorilas Andreas , Howarth David H C , Diamandis Eleftherios P 
Published: January 2020

Abstract
Background: Human kallikrein 4 (gene, KLK4; protein, hK4), a recently discovered member of the kallikrein gene family, shares many characteristics with prostate-specific antigen, the best available marker for prostate cancer. Because the protein has not been detected in any human tissue, we attempted to develop immunologic methods for hK4 analysis and use them to detect hK4 in healthy and cancerous tissue extracts and biological fluids.
Methods: We extracted total RNA from 20 pairs of matched (healthy–cancer) prostate tissue samples. KLK4 cDNA was amplified by reverse transcription-PCR (RT-PCR) and cloned in a pPICZαA expression vector. We then transformed the construct product into Pichia pastoris yeast strains and induced secreted recombinant protein production by addition of methanol. We purified the recombinant protein by nickel ion-affinity chromatography and used it as an immunogen in rabbits and mice to generate polyclonal anti-hK4 antibodies. These antibodies were used to develop a sandwich-type immunoassay suitable for hK4 quantification in biological fluids and tissue extracts.
Results: The immunoassay had a detection limit of 0.1 μg/L. We detected hK4 in 10 of 21 matched (healthy–cancer) prostate tissues, and hK4 was frequently higher in healthy tissues. In one matched-sample pair, the hK4 content was relatively high in both the healthy [4.62 μg/g of total protein (TP)] and the cancerous (1.22 μg/g of TP) prostate tissue. Among tissue extracts, we found the highest concentrations of hK4 in healthy (0.0–4.62 μg/g of TP) and cancerous (0.0–1.72 μg/g of TP) prostatic extracts and in placental extracts (0.0–0.05 μg/g of TP). We also detected traces of hK4 protein immunoreactivity in amniotic fluid (&lt;0.1–0.6 μg/L), human breast milk (&lt;0.1–0.75 μg/L), and seminal plasma (0.2–0.9 μg/L). Immunohistochemical studies showed cytoplasmic staining for hK4 protein in both malignant and benign epithelial cells of the prostate. However, we did not detect hK4 in cerebrospinal fluid, healthy and cancerous ovarian tissue extracts, and many other human tissue extracts.
Conclusions: hK4 protein is present in some prostatic tissue extracts but at relatively low concentrations, although KLK4 mRNA is readily detectable by RT-PCR. We propose that the protein either is not synthesized efficiently or is degraded very quickly.
Commutability Assessment of Potential Reference Materials Using a Multicenter Split-Patient-Sample Between-Field-Methods (Twin-Study) Design: Study within the Framework of the Dutch Project “Calibration 2000”
Authors: Baadenhuijsen Henk , Steigstra Herman , Cobbaert Christa , Kuypers Aldy , Weykamp Cas , Jansen Rob 
Published: January 2020

Abstract
Background: The Dutch project “Calibration 2000” aims at harmonization of laboratory results via calibration by development of commutable, matrix-based, secondary reference materials. An alternative approach to the NCCLS EP14 protocol for studying commutability of reference materials is presented, the “twin-study design”, which in essence is a multicenter, split-patient-sample, between-field-methods protocol.
Methods: The study consisted of the simultaneous analysis of fresh patient sera and potential reference materials (PRMs) for HDL-cholesterol (HDL-C) by 86 laboratories forming 43 laboratory couples. Six subgroups of method combinations were formed. The patient sera were selected and interchanged by each laboratory couple. The PRMs consisted of three types: C37, prepared according to the NCCLS C37 protocol; Fro, frozen selectively pooled human serum; and Lyo, which was the same serum pool as Fro but lyophilized in the presence of sucrose. All PRMs were provided in three HDL-C concentrations. The regression line residuals for the PRMs were normalized by expressing them as multiples of the state-of-the-art within laboratory SD (SDSA). In addition, the extra contribution of each PRM to the total measurement uncertainty, CVNetto, was calculated.
Results: Averaged over the three PRM concentrations, 1.6% of the C37 residuals were outside the 3 SDSA limit. For the Fro and Lyo PRMs, these values were 2.4% and 11.1%. CVNetto values for C37, Fro, and Lyo were 2.9%, 4.3%, and 5.3%, respectively.
Conclusions: The present twin-study design, as a practical alternative to the NCCLS EP14 protocol, is a viable way of studying commutability characteristics of PRMs. The study suggests that the C37 PRMs are the best candidates for a future reference material.
Artificial intelligence in medical imaging: A radiomic guide to precision phenotyping of cardiovascular disease
Authors: Oikonomou Evangelos K , Siddique Musib , Antoniades Charalambos 
Published: January 2020

AbstractRapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.
Coronary microvascular dysfunction in hypertrophy and heart failure
Authors: Camici Paolo G , Tschöpe Carsten , Di Carli Marcelo F , Rimoldi Ornella , Van Linthout Sophie 
Published: January 2020

Abstract
Left ventricular (LV) hypertrophy (LVH) is a growth in left myocardial mass mainly caused by increased cardiomyocyte size. LVH can be a physiological adaptation to physical exercise or a pathological condition either primary, i.e. genetic, or secondary to LV overload. Patients with both primary and secondary LVH have evidence of coronary microvascular dysfunction (CMD). The latter is mainly due to capillary rarefaction and adverse remodelling of intramural coronary arterioles due to medial wall thickening with an increased wall/lumen ratio. An important feature of this phenomenon is the diffuse nature of this remodelling, which generally affects the coronary microvessels in the whole of the left ventricle. Patients with LVH secondary to arterial hypertension can develop both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). These patients can develop HFrEF via a ‘direct pathway’ with an interval myocardial infarction and also in its absence. On the other hand, patients can develop HFpEF that can then progress to HFrEF with or without interval myocardial infarction. A similar evolution towards LV dysfunction and both HFpEF and HFrEF can occur in patients with hypertrophic cardiomyopathy, the most common genetic cardiomyopathy with a phenotype characterized by massive LVH. In this review article, we will discuss both the experimental and clinical studies explaining the mechanisms responsible for CMD in LVH as well as the evidence linking CMD with HFpEF and HFrEF.
Prognostic power of left atrial strain in patients with acute heart failure
Authors: Park Jae-Hyeong , Hwang In-Chang , Park Jin Joo , Park Jun-Bean , Cho Goo-Yeong 
Published: January 2020

Abstract

Aims
Left atrial (LA) dysfunction can be associated with left ventricular (LV) disorders; however, its clinical significance has not been well-studied in patients with acute heart failure (AHF). We evaluated prognostic power of peak atrial longitudinal strain (PALS) of the left atrium according to heart failure (HF) phenotypes and atrial fibrillation (AF).

Methods and results
From an AHF registry with 4312 patients, we analysed PALS in 3818 patients. Patients were categorized into PALS tertiles. We also divided the patients according to HF phenotypes [HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), or HF with preserved ejection fraction (HFpEF)] and presence of AF. The primary outcomes were all-cause mortality and HF hospitalization. PALS was weakly but significantly correlated with LA volume index (r = −0.310, P &lt; 0.001), E/e′ (r = −0.245, P &lt; 0.001), and LV ejection fraction (r = 0.371, P &lt; 0.001). A total of 2016 patients (52.8%) experienced adverse clinical events during median follow-up duration of 30.6 months (interquartile ranges 11.6–54.4 months). In the multivariate analysis, PALS was a significant predictor of events [hazard ratio (HR) 0.984, 95% confidence interval (CI) 0.971–0.996; P = 0.012]. Patients with the lowest tertile (HR 1.576, 95% CI 1.219–2.038; P &lt; 0.001) had a higher number of events than those with the highest tertile in the multivariate analysis. In the subgroup analysis, however, PALS was not a prognosticator (HR 0.987, 95% CI 0.974–1.000; P = 0.056) in AF patients. The prognostic power of PALS was not different between HFrEF (HR 0.977, 95% CI 0.969–0.974; P &lt; 0.001), HFmrEF (HR 0.984, 95% CI 0.972–0.996; P = 0.008), and HFpEF (HR 0.980, 95% CI 0.973–0.987; P &lt; 0.001, P for interaction = 0.433).

Conclusion
PALS was a significant prognostic marker in AHF patients. The prognostic power was similar regardless of HF phenotypes, but PALS was not associated with clinical events in AF patients.
Preclosing of the femoral artery allows total percutaneous venoarterial extracorporeal membrane oxygenation and prevents groin wound infection after lung transplantation
Authors: Pellenc Quentin , Girault Antoine , Roussel Arnaud , Aguir Sonia , Cerceau Pierre , Longrois Dan , Mal Hervé , Mordant Pierre , Castier Yves 
Published: January 2020

Abstract

OBJECTIVES
In lung transplantation (LT), femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) usually requires an open approach that may be associated with severe groin wound infection. In endovascular aortic procedures, preclosing of the femoral artery (PFA) with vascular closure devices allows the percutaneous insertion and withdrawal of large-bore cannulae. We sought to evaluate whether this innovative technique could be applied in the specific setting of LT to achieve total percutaneous VA-ECMO and decrease groin wound infection.

METHODS
We conducted a retrospective study of a prospective database including patients who underwent LT in our centre from January 2011 to December 2017. Patients who underwent peripheral VA-ECMO using the PFA technique after January 2014 (PFA group, n = 106) were compared to those who underwent peripheral VA-ECMO using open cannulation and/or decannulation before January 2014 (non-PFA group, n = 48). The primary end point was the rate of technical success defined as total percutaneous VA-ECMO. Secondary end points included groin wound infections and delayed vascular complications.

RESULTS
The PFA technique was technically successful in 98 patients (92.5%). As compared with the non-PFA group, the PFA group was characterized by a similar rate of vascular complications (16.6% vs 11.3%, P = 0.360) and a decreased rate of groin wound infection (18.9% vs 0%, P &lt; 0.001). In multivariate analysis, risk factors associated with vascular complications following PFA included female sex, peripheral arterial disease and ECMO duration.

CONCLUSIONS
In LT patients, PFA is associated with a high rate of total percutaneous VA-ECMO, thus preventing the occurrence of groin wound infection.
Early protein expression profile in bronchoalveolar lavage fluid and clinical outcomes in primary graft dysfunction after lung transplantation
Authors: Frick Anna E , Verleden Stijn E , Ordies Sofie , Sacreas Annelore , Vos Robin , Verleden Geert M , Vanaudenaerde Bart M , Claes Sandra , Schols Dominique , Van Raemdonck Dirk E , Neyrinck Arne P 
Published: January 2020

AbstractOBJECTIVESPrimary graft dysfunction (PGD) remains a major post-transplant complication and is associated with increased morbidity and mortality. Mechanisms evoking PGD are not completely clear, but inflammation plays a central role. We investigated the association between PGD and inflammatory proteins present in immediate postoperative bronchoalveolar lavage.METHODSAll double-lung recipients transplanted at our institution from 2002 to 2018 were included in our study. We retrospectively selected 80 consecutive lung transplant recipients with different PGD grades (n = 20 for each PGD grades 0–1 to 2–3). In bronchoalveolar lavage performed within the first 24 h after donor aortic cross-clamping following lung transplantation, concentrations of 30 cytokines, chemokines and growth factors were assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with donor and recipient demographics and outcomes. For analysis, 2 groups were defined: ‘mild’ PGD (grade 0–1) and ‘severe’ PGD (grades 2–3).RESULTSSignificant differences between mild and severe PGD were found in 8 biomarkers [interleukin (IL)-6, IL-10, IL-13, eotaxin, granulocyte colony-stimulating factor, interferon γ, macrophage inflammatory protein 1α, surfactant protein D (SP-D); P &lt; 0.05]. Increased IL-10 and IL-13, but none of the other proteins, were associated with short-term outcome (longer time to extubation; P = 0.005 and P &lt; 0.0001; increased intensive care unit stay; P = 0.012 and P &lt; 0.0001; and hospital stay; P = 0.041 and P = 0.002). There were no significant differences in donor and recipient characteristics between the groups.CONCLUSIONSExpression profiles of key inflammatory mediators in bronchoalveolar lavage fluid differed significantly between lung transplant recipients with severe versus mild PGD and correlated with clinical outcome variables. Further research should focus on the early mechanisms leading to PGD.
Exploring Community-Dwelling Older Adults’ Considerations About Values and Preferences for Future End-of-Life Care: A Study from Sweden
Authors: Eneslätt Malin , Helgesson Gert , Tishelman Carol 
Published: January 2020

Abstract

Background and Objectives
There is a substantial body of research on advance care planning (ACP), often originating from English-speaking countries and focused on health care settings. However, studies of content of ACP conversations in community settings remain scarce. We therefore explore community-dwelling, older adults’ reasoning about end-of-life (EoL) values and preferences in ACP conversations.

Research Design and Methods
In this participatory action research project, planned and conducted in collaboration with national community-based organizations, we interviewed 65 older adults without known EoL care needs, about their values and preferences for future EoL care. Conversations were stimulated by sorting and ranking statements in a Swedish version of GoWish cards, called the DöBra cards, and verbatim transcripts were analyzed inductively.

Results
While participants shared some common preferences about EoL care, there was great variation among individuals in how they reasoned. Although EoL preferences and prioritizations could be identical, different individuals explained these choices very differently. We exemplify this variation using data from four participants who discussed their respective EoL preferences by focusing on either physical, social, existential, or practical implications.

Discussion and Implications
A previously undocumented benefit of the GoWish/DöBra cards is how the flexibility of the card statements support substantial discussion of an individual’s EoL preferences and underlying values. Such in-depth descriptions of participants’ reasoning and considerations are important for understanding the very individual nature of prioritizing EoL preferences. We suggest future users of the DöBra/GoWish cards consider the underlying reasoning of individuals’ prioritizations to strengthen person-centeredness in EoL conversations and care provision.