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)

Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production

Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1 alpha. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1 alpha. We also identified a requirement for cystathionine-gamma-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H2S) production. H2S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.11Ysciescopu

Two-degree-of-freedom ℓ2-optimal tracking with preview

A simple SISO two-degree-of-freedom pole-placement design method is presented that provides ℓ2-optimal tracking of a given reference signal. The closed-loop pole locations are first chosen by the system designer. The closed-loop zeros are then placed in an optimal fashion by a computationally inexpensive algorithm to achieve asymptotic tracking with an optimal transient response. The preview approach, which has become a common method for dealing with systems which have non-minimum phase behavior, can then optionally be used to further improve the transient behavior for both minimum phase and non-minimum phase systems. Unlike previous results based on the preview approach, the solution presented here takes into consideration the closed-loop pole dynamics, and is ℓ2 optimal with respect to all other two-degree-of-freedom preview controllers with the same closed-loop poles. A simple solution to the H2 model matching problem, where the design parameter Q is not rational, but polynomial, is the heart of the solution method

Estimation of resting energy expenditure using predictive equations in critically ill children ::results of a systematic review

Provision of adequate energy intake to critically ill children is associated with improved prognosis, but resting energy expenditure (REE) is rarely determined by indirect calorimetry (IC) due to practical constraints. Some studies have tested the validity of various predictive equations that are routinely used for this purpose, but no systematic evaluation has been made. Therefore, we performed a systematic review of the literature to assess predictive equations of REE in critically ill children. We systematically searched the literature for eligible studies, and then we extracted data and assigned a quality grade to each article according to guidelines of the Academy of Nutrition and Dietetics. Accuracy was defined as the percentage of predicted REE values to fall within ±10% or ±15% of the measured energy expenditure (MEE) values, computed based on individual participant data. Of the 993 identified studies, 22 studies testing 21 equations using 2326 IC measurements in 1102 children were included in this review. Only 6 equations were evaluated by at least 3 studies in critically ill children. No equation predicted REE within ±10% of MEE in >50% of observations. The Harris–Benedict equation overestimated REE in two‐thirds of patients, whereas the Schofield equations and Talbot tables predicted REE within ±15% of MEE in approximately 50% of observations. In summary, the Schofield equations and Talbot tables were the least inaccurate of the predictive equations. We conclude that a new validated indirect calorimeter is urgently needed in the critically ill pediatric population.

Suspected Case of Drug-Induced Acute Respiratory Distress Syndrome following Trimethoprim-Sulfamethoxazole Treatment

In this article, we reported the case of a child patient who was admitted to our PICU for severe acute respiratory distress syndrome (ARDS) while being treated with trimethoprim-sulfamethoxazole (TMP-SMX) for osteomyelitis. Based on the timing of exposure, lack of alternative explanations, and clinical course similar to previously described cases, we suspect that TMP-SMX may have triggered ARDS. Despite meeting criteria for extracorporeal membrane oxygenation cannulation, conservative management and lung recruitment with high-frequency percussive ventilation could avoid the latter

Age is not a good predictor of irreversibility of pulmonary hypertension in congenital cardiac malformations with left-to-right shunt

OBJECTIVE Congenital cardiac malformations with high pulmonary blood flow and pressure due to left-to-right shunts are usually repaired in early infancy for both the benefits of early relief of heart failure and the fear that the concomitant pulmonary hypertension may become irreversible unless these defects are corrected at an early age. Age, however, has been a poor predictor of irreversibility of pulmonary hypertension in our experience, which is presented here. DESIGN A retrospective observational study. We defined "late" as age ≥2 years. We examined clinical, echocardiographic, and hemodynamic data from all patients aged ≥2 years with such malformations referred to us from 2004 untill 2015. SETTING Department of Pediatric Cardiology and Cardiac Surgery, University Hospital of Vaud, Lausanne, Switzerland. PATIENTS There were 39 patients, aged 2-35 years (median: 5 years), without chromosomal abnormalities. All had malformations amenable to biventricular repair, and all had high systolic right ventricular pressures by echocardiography prior to referral. INTERVENTIONS All patients underwent catheterization for assessment of pulmonary hypertension. If this was reversible, surgical correction was offered. OUTCOME MEASURES (1) Operability based on reversibility of pulmonary hypertension. (2) When surgery was offered, mortality and evidence of persisting postoperative pulmonary hypertension were examined. RESULTS Eighteen patients had no pulmonary hypertension, 5 of variable ages were inoperable due to irreversible pulmonary hypertension, and 16 had reversible pulmonary hypertension. Therefore, 34 patients underwent corrective surgery, with no immediate or late mortality. Pulmonary arterial and right ventricular pressures decreased noticeably in all operated patients. This is sustained to date; they are all asymptomatic with no echocardiographic evidence of pulmonary hypertension at a median follow-up of 7 years (range 2-13 years). CONCLUSIONS Pulmonary hypertension may still be reversible in many surprisingly old patients with left-to-right shunt lesions, who may therefore still be operable