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1.
Seth D. Rhoades Aalim M. Weljie 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):183
Introduction
Both reverse-phase and HILIC chemistries are deployed for liquid-chromatography mass spectrometry (LC–MS) metabolomics analyses, however HILIC methods lag behind reverse-phase methods in reproducibility and versatility. Comprehensive metabolomics analysis is additionally complicated by the physiochemical diversity of metabolites and array of tunable analytical parameters.Objective
Our aim was to rationally and efficiently design complementary HILIC-based polar metabolomics methods on multiple instruments using design of experiments (DoE).Methods
We iteratively tuned LC and MS conditions on ion-switching triple quadrupole (QqQ) and quadrupole-time-of-flight (qTOF) mass spectrometers through multiple rounds of a workflow we term Comprehensive optimization of LC–MS metabolomics methods using design of experiments (COLMeD). Multivariate statistical analysis guided our decision process in the method optimizations.Results
LC–MS/MS tuning for the QqQ method on serum metabolites yielded a median response increase of 161.5 % (p < 0.0001) over initial conditions with a 13.3 % increase in metabolite coverage. The COLMeD output was benchmarked against two widely used polar metabolomics methods, demonstrating total ion current increases of 105.8 and 57.3 %, with median metabolite response increases of 106.1 and 10.3 % (p < 0.0001 and p < 0.05 respectively). For our optimized qTOF method, 22 solvent systems were compared on a standard mix of physiochemically diverse metabolites, followed by COLMeD optimization, yielding a median 29.8 % response increase (p < 0.0001) over initial conditions.Conclusions
The COLMeD process elucidated response tradeoffs, facilitating improved chromatography and MS response without compromising separation of isobars. COLMeD is efficient, requiring no more than 20 injections in a given DoE round, and flexible, capable of class-specific optimization as demonstrated through acylcarnitine optimization within the QqQ method.2.
Elif Erdem Ibrahim Inan Harbiyeli Hazal Boral Macit Ilkit Meltem Yagmur Reha Ersoz 《Mycopathologia》2018,183(3):521-527
Purpose
To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.Design
Retrospective case series in a tertiary university hospital.Participants
CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.Methods
The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.Main Outcome Measures
Grade of the corneal infection.Results
Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).Conclusions
The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.3.
Dimitrios J. Floros Paul R. Jensen Pieter C. Dorrestein Nobuhiro Koyama 《Metabolomics : Official journal of the Metabolomic Society》2016,12(9):145
Introduction
Natural products from culture collections have enormous impact in advancing discovery programs for metabolites of biotechnological importance. These discovery efforts rely on the metabolomic characterization of strain collections.Objective
Many emerging approaches compare metabolomic profiles of such collections, but few enable the analysis and prioritization of thousands of samples from diverse organisms while delivering chemistry specific read outs.Method
In this work we utilize untargeted LC–MS/MS based metabolomics together with molecular networking to inventory the chemistries associated with 1000 marine microorganisms.Result
This approach annotated 76 molecular families (a spectral match rate of 28 %), including clinically and biotechnologically important molecules such as valinomycin, actinomycin D, and desferrioxamine E. Targeting a molecular family produced primarily by one microorganism led to the isolation and structure elucidation of two new molecules designated maridric acids A and B.Conclusion
Molecular networking guided exploration of large culture collections allows for rapid dereplication of know molecules and can highlight producers of uniques metabolites. These methods, together with large culture collections and growing databases, allow for data driven strain prioritization with a focus on novel chemistries.4.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.5.
Dorothea Lesche Roland Geyer Daniel Lienhard Christos T. Nakas Gaëlle Diserens Peter Vermathen Alexander B. Leichtle 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):159
Background
Centrifugation is an indispensable procedure for plasma sample preparation, but applied conditions can vary between labs.Aim
Determine whether routinely used plasma centrifugation protocols (1500×g 10 min; 3000×g 5 min) influence non-targeted metabolomic analyses.Methods
Nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS) data were evaluated with sparse partial least squares discriminant analyses and compared with cell count measurements.Results
Besides significant differences in platelet count, we identified substantial alterations in NMR and HRMS data related to the different centrifugation protocols.Conclusion
Already minor differences in plasma centrifugation can significantly influence metabolomic patterns and potentially bias metabolomics studies.6.
Strategies to assess and optimize stability of endogenous amines during cerebrospinal fluid sampling
Marek J. Noga Ronald Zielman Robin M. van Dongen Sabine Bos Amy Harms Gisela M. Terwindt Arn M. J. M. van den Maagdenberg Thomas Hankemeier Michel D. Ferrari 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):44
Introduction
Metabolic profiling of cerebrospinal fluid (CSF) is a promising technique for studying brain diseases. Measurements should reflect the in vivo situation, so ex vivo metabolism should be avoided.Objective
To investigate the effects of temperature (room temperature vs. 4 °C), centrifugation and ethanol, as anti-enzymatic additive during CSF sampling on concentrations of glutamic acid, glutamine and other endogenous amines.Methods
CSF samples from 21 individuals were processed using five different protocols. Isotopically-labeled alanine, isoleucine, glutamine, glutamic acid and dopamine were added prior to sampling to trace any degradation. Metabolomics analysis of endogenous amines, isotopically-labeled compounds and degradation products was performed with a validated LC–MS method.Results
Thirty-six endogenous amines were quantified. There were no statistically significant differences between sampling protocols for 31 out of 36 amines. For GABA there was primarily an effect of temperature (higher concentrations at room temperature than at 4 °C) and a small effect of ethanol (lower concentrations if added) due to possible degradation. O-phosphoethanolamine concentrations were also lower when ethanol was added. Degradation of isotopically-labeled compounds (e.g. glutamine to glutamic acid) was minor with no differences between protocols.Conclusion
Most amines can be considered stable during sampling, provided that samples are cooled immediately to 4 °C, centrifuged, and stored at ??80 °C within 2 h. The effect of ethanol addition for more unstable metabolites needs further investigation. This was the first time that labeled compounds were used to monitor ex vivo metabolism during sampling. This is a useful strategy to study the stability of other metabolites of interest.7.
Masahito Uji Yukihiro Yokoyama Katsuya Ohbuchi Kazuaki Tsuchiya Chiharu Sadakane Chika Shimobori Masahiro Yamamoto Masato Nagino 《Metabolomics : Official journal of the Metabolomic Society》2017,13(12):155
Introduction
In patients with obstructive jaundice, biliary drainage sometimes fails to result in improvement. A pharmaceutical-grade choleretic herbal medicine, Inchinkoto (ICKT), has been proposed to exert auxiliary effects on biliary drainage; however, its effects are variable among patients.Objectives
The aim of this study is to explore serum biomarkers that are associated with pharmaceutical efficacy of ICKT.Methods
Obstructive jaundice patients who underwent external biliary decompression were enrolled (n?=?37). ICKT was given orally 3 times a day at daily dose of 7.5 g. Serum and bile samples were collected before, 3 h after, and 24 h after ICKT administration. The concentrations of total bilirubin, direct bilirubin, and total bile acid in bile specimens were measured. Metabolites in serum samples were comprehensively profiled using LC–MS/MS and GC–MS/MS. Pharmacokinetic analysis of major ICKT components was also performed.Results
ICKT administration significantly decreased serum ALT and increased bile volume after 24 h. The serum concentrations of ICKT components were not well correlated with the efficacy of ICKT. However, the ratio of 2-hydroxyisobutyric acid to arachidonic acid and the ratio of glutaric acid to niacinamide, exhibited good performance as biomarkers for the efficacy of ICKT on bile flow and ALT, respectively. Additionally, comprehensive correlation analysis revealed that serum glucuronic acid was highly correlated with serum total bilirubin, suggesting that this metabolite may be deeply involved in the pathogenesis of jaundice.Conclusions
The present study indicates that ICKT is efficacious and provides candidates for predicting ICKT efficacy. Further validation studies are warranted.8.
Andreas Entenmann Miriam Michel Bruno Ismer Roman Gebauer 《Biomedical engineering online》2017,16(1):139
Background
R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP–VS) may be observed during routine clinical practice.Objectives
The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP–VS intervals.Methods
Calculated AP–VS intervals were compared with those predicted by experienced pediatric cardiologist.Results
A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP–VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP–VS interval could not be predicted by experienced observers. In our newly proposed technique the AP–VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (? 0.4 ms/bpm) between the two extreme levels.Conclusions
Adjusting the AP–VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP–VS interval.9.
Stéphane Grison Gaëlle Favé Matthieu Maillot Olivia Delissen Éric Blanchardon Isabelle Dublineau Jocelyne Aigueperse Sandra Bohand Jean-Charles Martin Maâmar Souidi 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):154
Introduction
Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake.Objectives
In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L?1; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose–effect pattern and identify additional potential biomarkers in urine samples.Methods
Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L?1). LC–MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages.Results
The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L?1. Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score.Conclusion
These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L?1.10.
Roberto Stella Gaud Dervilly-Pinel Davide Bovo Eleonora Mastrorilli Anne-Lise Royer Roberto Angeletti Bruno Le Bizec Giancarlo Biancotto 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):80
Introduction
The surveillance of illegal anabolic practices in bovine meat production is necessary to guarantee consumers’ health. Screening strategies based on the recognition of indirect biological effects are considered by the community as promising tools to overcome some limitations of classical analytical methods and might therefore concur to ensure safer food for the consumer.Objectives
The present work aims at characterizing the metabolic profile induced in liver by administration of anabolic steroids, and at identifying potential disturbances in the hepatic metabolism.Methods
A total of 32 liver samples, 16 from untreated bulls and 16 from bulls treated with an ear implant (Revalor-XS®) containing trenbolone acetate (200 mg) and β-estradiol (40 mg), were analyzed following a LC–MS-based metabolomic analysis combining RP and HILIC chromatographic separations. Different multivariate statistical tools were applied to the datasets to select common metabolites that may be considered as potential markers based on their significant changes in concentrations after administration of sexual steroids.Results
Eight candidate markers were identified. Moreover, a subset of four markers was also validated by a different laboratory that performed the same analysis using an independent instrumental and elaboration platform, confirming the robustness of the results achieved.Conclusion
This study was performed mimicking experimental conditions that may be used during a potential misuse practice. It is promising in the objective of setting up an analytical strategy to highlight sexual steroids abuse in livestock animals.11.
Objectives
To study the binding of pranlukast to hRKIP and its regulatory role in the Raf1/MEK/ERK signal pathway.Results
NMR and fluorescence experiments demonstrated hRKIP could bind pranlukast with a binding constant of 1016 mM?1. Residues (Y81, S109 and Y181) on the conserved ligand-binding pocket of hRKIP played a crucial role in binding pranlukast, and their mutations reduced the binding affinity more than 85 %. Furthermore, 25 μM pranlukast could up-regulate the ERK phosphorylation by about 17 %.Conclusion
Pranlukast may be used as a potential drug precursor for treating hRKIP involved diseases.12.
Khadidja Boualem Steve Labrie Patrick Gervais Yves Waché Jean-François Cavin 《Biotechnology letters》2016,38(2):329-335
Objective
To study the ability of a commercial Penicillium camemberti strain, used for Camembert type cheese ripening, to produce conidia during growth in liquid culture (LC), in media containing different sources of nitrogen as, industrially, conidia are produced by growth at the surface of a solid state culture because conidiation in stirred submerged aerobic LC is not known.Results
In complex media containing peptic digest of meat, hyphae ends did not differentiate into phialides and conidia. Contrarily, in a synthetic media containing KNO3 as sole nitrogen source, hyphae ends differentiated into phialides producing 0.5 × 107 conidia/ml. Conidia produced in LC were 25 % less hydrophobic than conidia produced in solid culture, and this correlates with a seven-times-lower expression of the gene rodA encoding hydrophobin RodA in the mycelium grown in LC.Conclusion
Conidiation of P. camembertii is stimulated in iquid medium containing KNO3 as sole source of nitrogen and therefore opens up opportunities for using liquid medium in commercial productions.13.
John M. Wentworth Naiara G. Bediaga Megan A. S. Penno Esther Bandala-Sanchez Komal N. Kanojia Konstantinos A. Kouremenos Jennifer J. Couper Leonard C. Harrison ENDIA Study Group 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):130
Background
Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.Method
Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.Results
Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.Conclusion
Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.14.
Objective
To investigate the cellulose modification process on kraft pulp during recycling by mono-endoglucanase.Results
Pichia pastoris expressing endoglucanase, EG1, was grown in a 10 l fermenter yielding a high carboxymethyl cellulase (CMCase) activity of 340 U mg?1. EG1-mediated modification of kraft pulp resulted in a paper sheet with the tensile index and burst index increased by 10 and 6.5 %, respectively. The kink index (indicating abrupt bends in fibres) of the enzyme-treated group decreased sharply by 45 % after the first recycling, compared with a reduction of only 1 % in the control group. Furthermore, EG1 treatment decreased the growth of crystallinity from 73.5 to 73.2 % and crystal size from 7.45 to 7.21 nm, which alleviated paper aging.Conclusion
Endoglucanase EG1 modifies the interfacial properties of fibers, which affects fibre morphology during the recycling process and improves the technical properties of the resulting pulp and paper.15.
Aim
This work aimed to investigate the role of arbuscular mycorrhizal fungi (AMF) in the uptake and accumulation of silicon (Si) in banana plants. Si is recognized as a significant element that helps plants resist stresses.Methods
A pot experiment compared the growth, Si and P accumulation of banana plants pre-colonized or not by an AMF and exposed or not to Si added to the growth substrate.Results
A marked increase in Si was noticed in pseudostem, leaves and roots of pre-colonized banana plants, in presence as well as in absence of Si added to the growth substrate. Without Si addition, this accumulation was 60 % and 45 % higher in pseudostem and leaves, respectively, while it was 47 % and 41 % in presence of Si added to the substrate. In roots, this increase was 23 % and 52 % in presence and absence of Si added to the substrate, respectively. Phosphorus content in shoots and roots was likewise significantly increased in presence of AMF or Si.Conclusion
Our findings revealed that pre-colonized banana plants accumulated more Si in shoot and roots than non-mycorrhizal plants and may thus represent a potential novel avenue to explore banana resistance to pests and diseases.16.
Objectives
To use permeabilized cells of the fission yeast, Schizosaccharomyces pombe, that expresses human UDP-glucose 6-dehydrogenase (UGDH, EC 1.1.1.22), for the production of UDP-glucuronic acid from UDP-glucose.Results
In cell extracts no activity was detected. Therefore, cells were permeabilized with 0.3 % (v/v) Triton X-100. After washing away all low molecular weight metabolites, the permeabilized cells were directly used as whole cell biocatalyst. Substrates were 5 mM UDP-glucose and 10 mM NAD+. Divalent cations were not added to the reaction medium as they promoted UDP-glucose hydrolysis. With this reaction system 5 mM UDP-glucose were converted into 5 mM UDP-glucuronic acid within 3 h.Conclusions
Recombinant permeabilized cells of S. pombe can be used to synthesize UDP-glucuronic acid with 100 % yield and selectivity.17.
Ray O. Bahado-Singh Stewart F. Graham BeomSoo Han Onur Turkoglu James Ziadeh Rupasri Mandal Anil Er David S. Wishart Philip L. Stahel 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):100
Introduction
Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.Objectives
Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.Methods
A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.Results
Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.Conclusion
Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.18.
A. F. B. E. Quast V. F. van Dijk A. A. M. Wilde R. E. Knops L. V. A. Boersma 《Netherlands heart journal》2017,25(5):312-317
Introduction
The latest European Society of Cardiology Guidelines recommend consideration of a wearable cardioverter-defibrillator (WCD) for patients with a poor left ventricular ejection fraction (LVEF) who are at risk of sudden arrhythmic death but are not eligible for an implantable defibrillator. For these patients a WCD can be an alternative to long-term hospitalisation.Purpose
To evaluate the use of WCD therapy in these patient groups in two Dutch centres.Methods
All consecutive patients treated with the WCD between 2009 and 2016 were included from two centres in the Netherlands. Data on events and compliance were collected retrospectively through home monitoring systems and adjudicated by the investigators.Results
A total of 79 patients were treated with a WCD. Common indications were newly diagnosed cardiomyopathy without optimal medical treatment in 46 patients (58.2%) and bridge to implantable cardioverter-defibrillator (ICD) implant in 33 patients (41.8%). Bridge to implant indications consisted of contraindications for immediate implantation such as infections (e.?g. previous device-related infections) and radiotherapy. Compliance was over 97% per day (median 23.3?h, 22.6–23.7), during a median of 79 days (50.0–109.8.0). Two patients (2.6%) received an appropriate shock (annual rate 13.6%), there was 1 (1.3%) inappropriate shock (annual rate 6.7%). In 24 patients (52.2%) without optimal medical treatment, the LVEF was sufficiently improved and ICD implant was avoided. Eight (10.1%) patients did not receive an ICD. In 45 patients an ICD was implanted (57.0%).Conclusion
WCD therapy provides a safe and effective treatment in outpatient setting for patients at high risk for sudden cardiac death and reduces the number of ICDs implanted.19.
F. A. Kortlandt C. C. van ’t Klooster A. L. M. Bakker M. J. Swaans J. C. Kelder T. L. de Kroon B. J. W. M. Rensing F. D. Eefting J. A. S. van der Heyden M. C. Post 《Netherlands heart journal》2016,24(7-8):475-480
Background
Surgical risk scores are used to identify high-risk patients for surgical mitral valve repair. There is no scoring system to estimate the mortality risk for patients undergoing percutaneous treatment. The aim of this analysis is to evaluate the predictive value of the EuroSCOREs and the Society of Thoracic Surgeons Predicted Risk of Mortality Score (STS) for periprocedural mortality in percutaneous edge-to-edge mitral valve repair.Methods
From 2009 to 2013, 136 high-risk patients were included who underwent 143 procedures. Observed periprocedural mortality was compared with predicted mortality using the logistic EuroSCORE, EuroSCORE II and STS. The predictive value was analysed by receiver operating characteristic curves for each score.Results
Observed periprocedural mortality was 3.5 %. The predicted surgical mortality risk was: 23.1 ± 15.7 % for the logistic EuroSCORE, 9.6 ± 7.7 % for the EuroSCORE II and 13.2 ± 8.2 % for the STS. The predictive value estimated by the area under the curve was: 0.55, 0.54 and 0.65 for the logistic EuroSCORE, EuroSCORE II and STS respectively. Severe pulmonary hypertension and acute procedural success were significant predictive parameters in univariate analysis.Conclusion
Contemporary surgical scores do not adequately predict periprocedural mortality for high-risk patients undergoing edge-to-edge mitral valve repair, but they can be used to help decision-making in the selection process for this procedure.20.
Liming Weng Yan Gong Jeffrey Culver Stephen J. Gardell Christopher Petucci Alison M. Morse Reginald F. Frye Stephen T. Turner Arlene Chapman Eric Boerwinkle John Gums Amber L. Beitelshees Peggy R. Borum Julie A. Johnson Timothy J. Garrett Lauren M. McIntyre Rhonda M. Cooper-DeHoff 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):160