Point-of-care hemostasis in children with congenital heart disease, the POCHEMO study : baseline reference values of thromboelastometry and impedance aggregometry

: Viscoelastic tests and impedance aggregometry allow coagulation evaluation at the bedside, but reference values are scarce in pediatrics. The aim of this study was to establish reference values of thromboelastometry and impedance aggregometry for this population and compare it between age groups. This prospective, single-center, observational study evaluates viscoelastic tests and impedance aggregometry in children with congenital heart disease. A total of 204 children were included with a median age of 3.6 years old. We provide references values for this population with median, percentile 2.5 and percentile 97.5. Infants demonstrate for extrinsic activity a shorter coagulation time (52 [49-55] vs. 56 [51-62] s, P = 0.007) and clot formation time (90 [71-118] vs. 113 [93-146] s, P < 0.0001) so as for intrinsic activity a shorter clot formation time (53 [44-69] vs. 75 [59-92] s, P < 0.0001). The maximal clot firmness was significantly stronger in infants for extrinsic (65 [61-69] vs. 59 [54-63] mm, P < 0.0001), intrinsic (68 [64-70] vs. 61 [57-65] mm, P < 0.0001), and fibrinogen (12 [9-16] vs. 10 [8-13] mm, P = 0.02) activities. Platelet aggregation was significantly higher in infants with an amplitude at 6 min of 28 [23-34] vs. 22 [15-27] Ω, P less than 0.0001, a maximum speed of 11 [9-13] vs. 7 [5-10] Ω/min, P less than 0.0001, and an area under the curve of 120 [92-135] vs. 86 [59-112] Ω min, P less than 0.0001. We provided the first reference values for impedance aggregometry and thromboelastometry in children with congenital heart disease. We showed that these infants tend to have accelerated coagulation and stronger clot firmness compared with older children, but this finding may have only minimal relevance when treating a bleeding child. Trial registration number: ClinicalTrials.gov (clinicaltrials.gov/ct2/show/NCT02387944)

LC-MSMS identification of small molecules: SmileMS, a small molecule identification platform applied to clinical toxicology

LLC-MSMS combined with library search approaches is getting popular as an alternative to existing methods in clinical toxicology, for the screening of toxics. Such screenings are traditionally operated in emergency units, where they act as an early diagnostic test of the patient condition. As a result, routine laboratories need robust and easy to use software solutions that can handle the complexity of spectra generated by LCMSMS as well as deliver high quality results in the shortest time possible. In this thesis, we present a small molecule identification platform called SmileMS. This platform was developed to be used in applications based on LC-MSMS identification but also to act as an exploration platform for further investigation in the field of small molecule identification. Throughout the conception of SmileMS, these investigations concerned four areas: the creation scoring models, the handling of spectral libraries, the theoretical fragmentation of molecules, and the setting of engineering strategies enabling software exploration of data

Laparoscopic surgery in a child with a failing Fontan circulation

A child with early failure of a Fontan circulation was listed for cardiac transplantation and then developed a subhepatic abscess. Surgical drainage was deemed necessary after the failure of an attempted percutaneous procedure. Following a multidisciplinary discussion, a laparoscopic technique was chosen to optimise postoperative recovery. To our knowledge, the literature does not describe any case of laparoscopic surgery in a patient with a failing Fontan circulation. This case report highlights the physiological variations involved with this management strategy, discusses the implications and risks, and offers some recommendations

X-Rank: a robust algorithm for small molecule identification using tandem mass spectrometry

The diversity of experimental workflows involving LC-MS/MS and the extended range of mass spectrometers tend to produce extremely variable spectra. Variability reduces the accuracy of compound identification produced by commonly available software for a spectral library search. We introduce here a new algorithm that successfully matches MS/MS spectra generated by a range of instruments, acquired under different conditions. Our algorithm called X-Rank first sorts peak intensities of a spectrum and second establishes a correlation between two sorted spectra. X-Rank then computes the probability that a rank from an experimental spectrum matches a rank from a reference library spectrum. In a training step, characteristic parameter values are generated for a given data set. We compared the efficiency of the X-Rank algorithm with the dot-product algorithm implemented by MS Search from the National Institute of Standards and Technology (NIST) on two test sets produced with different instruments. Overall the X-Rank algorithm accurately discriminates correct from wrong matches and detects more correct substances than the MS Search. Furthermore, X-Rank could correctly identify and top rank eight chemical compounds in a commercially available test mix. This confirms the ability of the algorithm to perform both a straight single-platform identification and a cross-platform library search in comparison to other tools. It also opens the possibility for efficient general unknown screening (GUS) against large compound libraries