LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

The timing of adiposity and changes in the life course on the risk of cancer.

Excess body weight has been established as a risk factor for at least twelve cancer sites, though questions remain as to the timing of associations for adiposity and cancer risk throughout the life course. We conducted a narrative review summarizing existing evidence to provide insights into the complex timing relationship between adiposity and risk of seven common obesity-related cancers. We considered five types of studies, including traditional epidemiologic studies examining adiposity at different time points, studies examining weight gain in specific life phases, studies examining weight loss over a period including from bariatric surgery, life course trajectory analysis, and Mendelian randomization studies. The results showed that lifetime excess body weight is associated with increased risk of cancers of endometrium, colorectum, liver, kidney, and pancreas. Early life obesity is one of the strongest risk factors for pancreatic cancer but less directly important than adult obesity for endometrial and kidney cancer. Interestingly, heavy weight during childhood, adolescence, and early adulthood is protective against pre- and postmenopausal breast cancer and possibly advanced prostate cancer. It is apparent that preventing weight gain later in adulthood would likely reduce risk of many cancers, including postmenopausal breast cancer, endometrial cancer, colorectal cancer (especially in men), liver cancer, kidney cancer, and probably advanced prostate cancer. Furthermore, weight loss even late in life may confer benefits for cancers of breast, endometrium, colorectum, and liver among patients with obesity, as mostly demonstrated by studies of bariatric surgery. Overall, maintaining a healthy weight throughout the life course will help prevent a large number of cancers.

MACC1 and Gasdermin-E (GSDME) regulate the resistance of colorectal cancer cells to irinotecan.

Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and metastasis of many solid cancer entities. High expression of MACC1 is found in colorectal cancer (CRC) tissues. So far, the role of MACC1 in CRC cell pyroptosis and resistance to irinotecan is unclear. The cleavage of Gasdermin-E (GSDME) is the main executors of activated pyroptosis. We found that GSDME enhanced CRC cell pyroptosis and reduced their resistance to irinotecan, while MACC1 inhibited the cleavage of GSDME and CRC cell pyroptosis, promoted CRC cell proliferation, and enhanced the resistance of CRC cells to irinotecan. Therefore, CRC cells with high MACC1 expression and low GSDME expression had higher resistance to irinotecan, while CRC cells with low MACC1 expression and high GSDME expression had lower resistance to irinotecan. Consistently, by analyzing CRC patients who received FOLFIRI (Fluorouracil + Irinotecan + Leucovorin) in combination with chemotherapy in the GEO database, we found that CRC patients with low MACC1 expression and high GSDME expression had higher survival rate. Our study suggests that the expression of MACC1 and GSDME can be used as detection markers to divide CRC patients into irinotecan resistant and sensitive groups, helping to determine the treatment strategy of patients.

Altered hippocampal subfield volumes in major depressive disorder with and without anhedonia.

BACKGROUND: Previous neuroimaging findings have demonstrated the association between anhedonia and the hippocampus. However, few studies have focused on the structural changes in the hippocampus in major depressive disorder (MDD) patients with anhedonia. Meanwhile, considering that multiple and functionally specialized subfields of the hippocampus have their own signatures, the present study aimed to investigate the volumetric alterations of the hippocampus as well as its subfields in MDD patients with and without anhedonia. METHODS: A total of 113 subjects, including 30 MDD patients with anhedonia, 40 MDD patients without anhedonia, and 43 healthy controls (HCs), were recruited in the study. All participants underwent high-resolution brain magnetic resonance imaging (MRI) scans, and the automated hippocampal substructure module in FreeSurfer 6.0 was used to evaluate the volumes of hippocampal subfields. We compared the volumetric differences in hippocampal subfields among the three groups by analysis of variance (ANOVA, post hoc Bonferroni), and partial correlation was used to explore the association between hippocampal subregion volumes and clinical characteristics. RESULTS: ANOVA showed significant volumetric differences in the hippocampal subfields among the three groups in the left hippocampus head, mainly in the cornu ammonis (CA) 1, granule cell layer of the dentate gyrus (GC-ML-DG), and molecular layer (ML). Compared with HCs, both groups of MDD patients showed significantly smaller volumes in the whole left hippocampus head. Interestingly, further exploration revealed that only MDD patients with anhedonia had significantly reduced volumes in the left CA1, GC-ML-DG and ML when compared with HCs. No significant difference was found in the volumes of the hippocampal subfields between MDD patients without anhedonia and HCs, either the two groups of MDD patients. However, no association between hippocampal subfield volumes and clinical characteristics was found in either the subset of patients with anhedonia or in the patient group as a whole. CONCLUSIONS: These preliminary findings suggest that MDD patients with anhedonia exhibit unique atrophy of the hippocampus and that subfield abnormalities in the left CA1 and DG might be associated with anhedonia in MDD.

Alterations of brainstem volume in patients with first-episode and recurrent major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a prevalent mental health condition characterized by recurrent episodes in a substantial proportion of patients. The number of previous episodes is one of the most crucial predictors of depression recurrence. However, the underlying neural mechanisms remain unclear. To date, there have been limited neuroimaging studies investigating morphological changes of the brainstem in patients with first-episode MDD (FMDD) and recurrent MDD (RMDD). This study aimed to examine volumetric changes of individual brainstem regions in relation to the number of previous episodes and disease duration. METHOD: A total of 111 individuals including 36 FMDD, 25 RMDD, and 50 healthy controls (HCs) underwent T1-weighted structural magnetic resonance imaging scans. A Bayesian segmentation algorithm was used to analyze the volume of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle (SCP), as well as the whole brainstem volume. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Partial correlation analyses were further conducted to identify associations between regional volumes and clinical features. RESULTS: The ANOVA revealed significant brainstem volumetric differences among three groups in the pons, midbrain, SCP, and the whole brainstem (F = 3.996 ~ 5.886, adjusted p = 0.015 ~ 0.028). As compared with HCs, both groups of MDD patients showed decreased volumes in the pons as well as the entire brainstem (p = 0.002 ~ 0.034), however, only the FMDD group demonstrated a significantly reduced volume in the midbrain (p = 0.003). Specifically, the RMDD group exhibited significantly decreased SCP volume when comparing to both FMDD (p = 0.021) group and HCs (p = 0.008). Correlation analyses revealed that the SCP volumes were negatively associated with the number of depressive episodes (r=-0.36, p < 0.01) and illness duration (r=-0.28, p = 0.035) in patients with MDD. CONCLUSION: The present findings provided evidence of decreased brainstem volume involving in the pathophysiology of MDD, particularly, volumetric reduction in the SCP might represent a neurobiological marker for RMDD. Further research is needed to confirm our observations and deepen our understanding of the neural mechanisms underlying depression recurrence.

Ultrathin CuF2 -Rich Solid-Electrolyte Interphase Induced by Cation-Tailored Double Electrical Layer toward Durable Sodium Storage.

Solid-electrolyte interphase (SEI) seriously affects battery's cycling life, especially for high-capacity anode due to excessive electrolyte decomposition from particle fracture. Herein, we report an ultrathin SEI (3-4 nm) induced by Cu+ -tailored double electrical layer (EDL) to suppress electrolyte consumption and enhance cycling stability of CuS anode in sodium-ion batteries. Unique EDL with SO3 CF3 -Cu complex absorbing on CuS in NaSO3 CF3 /diglyme electrolyte is demonstrated by in situ surface-enhanced Raman, Cyro-TEM and theoretical calculation, in which SO3 CF3 -Cu could be reduced to CuF2 -rich SEI. Dispersed CuF2 and F-containing compound can provide good interfacial contact for formation of ultrathin and stable SEI film to minimize electrolyte consumption and reduce activation energy of Na+ transport. As a result, the modified CuS delivers high capacity of 402.8 mAh g-1 after 7000 cycles without capacity decay. The insights of SEI construction pave a way for high-stability electrode.

Aberrant interhemispheric functional connectivity in major depressive disorder with and without anhedonia.

OBJECTIVE: Anhedonia is a core feature of major depressive disorder (MDD), and as a subtype of depression, MDD with anhedonia may have exceptional neurobiological mechanisms. However, the neuropathology of anhedonia in MDD remains unclear. Thus, this study aimed to investigate the brain functional differences between MDD with and without anhedonia. METHODS: A total of 62 individuals including 22 MDD patients with anhedonia, 20 MDD patients without anhedonia, and 20 healthy controls (HCs) were recruited for this study. All participants underwent 3.0-T functional magnetic resonance imaging scan. Voxel-mirrored homotopic connectivity (VMHC) was employed to quantitatively describe bilateral functional connectivity. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. RESULTS: The ANOVA revealed significant VMHC differences among three groups in the bilateral middle temporal gyrus (MTG), superior frontal gyrus (SFG), and inferior parietal lobule (IPL) (F = 10.47 ~ 15.09, p < 0.05, AlphaSim corrected). Relative to HCs, MDD with anhedonia showed significantly decreased VMHC in the bilateral MTG (t = -5.368, p < 0.05, AlphaSim corrected), as well as increased VMHC in the bilateral SFG (t = -4.696, p < 0.05, AlphaSim corrected). Compared to MDD without anhedonia, MDD with anhedonia showed significantly decreased VMHC in the bilateral MTG and IPL (t = -5.629 ~ -4.330, p < 0.05, AlphaSim corrected), while increased VMHC in the bilateral SFG (t = 3.926, p < 0.05, AlphaSim corrected). However, no significant difference was found between MDD without anhedonia and HCs. CONCLUSION: The present findings suggest that MDD with and without anhedonia exhibit different patterns of interhemispheric connectivity. Anhedonia in MDD is related to aberrant interhemispheric connectivity within brain regions involved in the frontal-temporal-parietal circuit.

Risk prediction models for colorectal cancer: Evaluating the discrimination due to added biomarkers.

Most risk prediction models for colorectal cancer (CRC) are based on questionnaires and show a modest discriminatory ability. Therefore, we aim to develop risk prediction models incorporating plasma biomarkers for CRC to improve discrimination. We assessed the predictivity of 11 biomarkers in 736 men in the Health Professionals Follow-up Study and 639 women in the Nurses' Health Study. We used stepwise logistic regression to examine whether a set of biomarkers improved the predictivity on the basis of predictors in the National Cancer Institute's (NCI) Colorectal Cancer Risk Assessment Tool. Model discrimination was assessed using C-statistics. Bootstrap with 500 randomly sampled replicates was used for internal validation. The models containing each biomarker generated a C-statistic ranging from 0.50 to 0.59 in men and 0.50 to 0.54 in women. The NCI model demonstrated a C-statistic (95% CI) of 0.67 (0.62-0.71) in men and 0.58 (0.54-0.63) in women. Through stepwise selection of biomarkers, the C-statistic increased to 0.70 (0.66-0.74) in men after adding growth/differentiation factor 15, total adiponectin, sex hormone binding globulin and tumor necrosis factor receptor superfamily member 1B (P for difference = 0.008); and increased to 0.62 (0.57-0.66) in women after further including insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 (P for difference = .06). The NCI + selected biomarkers model was internally validated with a C-statistic (95% CI) of 0.73 (0.70-0.77) in men and 0.66 (0.61-0.70) in women. Circulating plasma biomarkers may improve the performance of risk factor-based prediction model for CRC.

Circulating liver function markers and colorectal cancer risk: A prospective cohort study in the UK Biobank.

Evidence links the liver to development of colorectal cancer (CRC). However, it remains unknown how liver function may influence CRC risk in the general population. We conducted a prospective cohort study in the UK Biobank of 375 693 participants who provided blood samples in 2006 to 2010. Circulating levels of liver function markers (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin [TBIL], gamma glutamyltransferase [GGT], alkaline phosphatase [ALP], total protein [TP] and albumin [ALB]) were measured. Incident cancer cases were identified through linkage to the national cancer registry up to 2019. Repeated biomarker measurements were available from a subset of 11 320 participants who were re-assessed in 2012 to 2013. After a median follow-up of 10.0 years, we documented 2662 cases of CRC. Circulating levels of ALT, AST, TBIL, GGT, TP and ALB at baseline were inversely associated with CRC risk (P < .01), with multivariable hazard ratio (95% confidence interval) comparing decile 10 vs 1 of 0.62 (0.51-0.75), 0.63 (0.53-0.75), 0.85 (0.72-1.02), 0.74 (0.61-0.89), 0.70 (0.59-0.84) and 0.66 (0.55-0.79), respectively. Strengthened associations were found after recalibration for repeated measurements. The associations appeared stronger for proximal colon cancer than distal colon cancer and rectal cancer, but consistent for early-, mid- and late-onset CRC. In a large cohort of general population, the UK Biobank, higher circulating levels of ALT, AST, TBIL, GGT, TP and ALB, largely within the normal range, were associated with a lower risk of CRC. The findings support a link between liver function and CRC, and may spur future research on the gut-microbiota-liver axis.

Serum lipid profiles and risk of colorectal cancer: a prospective cohort study in the UK Biobank.

BACKGROUND: It remains unclear whether serum lipids influence colorectal cancer (CRC) risk. METHODS: We conducted a prospective cohort study of 380,087 adults aged 40-69 years in the UK Biobank. Serum high-density cholesterol, low-density cholesterol, total cholesterol, triglycerides, and apolipoprotein A and B were measured. We used Cox proportional hazard models to estimate the multivariable hazard ratios (HRs) of CRC according to one standard deviation (SD) increment in serum lipids. We conducted subgroup analysis by tumour anatomical subsites. RESULTS: During a median of 10.3 years of follow-up, we documented 2667 incident CRC cases. None of the lipid biomarkers was associated with the risk of CRC after adjusting for potential confounding factors, including body mass index and waist circumference. When assessed by cancer subsites, serum triglycerides was associated with an increased risk of cancer in the caecum and transverse colon, with the HR of 1.12 (95% CI, 1.00-1.25) and 1.29 (95% CI, 1.09-1.53), respectively; and apolipoprotein A was associated with a lower risk of hepatic flexure cancer (HR, 0.73, 95% CI, 0.56-0.96). CONCLUSIONS: Serum lipid profiles were not associated with colorectal cancer risk after adjusting for obesity indicators. The potential subsite-specific effects of triglycerides and apolipoprotein A require further confirmation.

Single photon counting compressive imaging using a generative model optimized via sampling and transfer learning.

Single photon counting compressive imaging, a combination of single-pixel-imaging and single-photon-counting technology, is provided with low cost and ultra-high sensitivity. However, it requires a long imaging time when applying traditional compressed sensing (CS) reconstruction algorithms. A deep-learning-based compressed reconstruction network refrains iterative computation while achieving efficient reconstruction. This paper proposes a compressed reconstruction network (OGTM) based on a generative model, adding sampling sub-network to achieve joint-optimization of sampling and generation for better reconstruction. To avoid the slow convergence caused by alternating training, initial weights of the sampling and generation sub-network are transferred from an autoencoder. The results indicate that the convergence speed and imaging quality are significantly improved. The OGTM validated on a single-photon compressive imaging system performs imaging experiments on specific and generalized targets. For specific targets, the results demonstrate that OGTM can quickly generate images from few measurements, and its reconstruction is better than the existing compressed sensing recovery algorithms, compensating defects of the generative models in compressed sensing.

Selected 2020 Highlights in Congenital Cardiac Anesthesia.

This article is a review of the highlights of pertinent literature published during the 12 months of 2020 that are of interest to the congenital cardiac anesthesiologist. After a search of the US National Library of Medicine's PubMed database, several topics emerged for which significant contributions were made in 2020. The authors of the present article considered the following topics noteworthy to be included in this review: pediatric cardiac care in the coronavirus disease 2019 era, the use of mechanical circulatory support in coronavirus disease 2019-related multisystem inflammatory syndrome in children, transfusion and coagulation management in children undergoing congenital heart surgery, and pulmonary vein stenosis.

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation.

Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications. Often, patients present for urgent surgery while taking medications including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants, which must be recognized, monitored, and managed. During extracorporeal circulation, appropriate anticoagulation, most commonly with heparin, is required to maintain blood flow and avoid thrombotic complications. However, anticoagulation and other effects of extracorporeal circuits can also have an undesired consequence of bleeding. Extracorporeal circulation leads to coagulopathy that may require therapy with blood products such as platelets, cryoprecipitate, and plasma in case a patient bleeds. Platelet dysfunction related to exposure to a foreign circuit is a primary concern, as is the development of acquired von Willebrand syndrome, which frequently remains undetected on routine testing. Hemorrhagic complications in ECMO, such as intracranial hemorrhage, pulmonary hemorrhage, and hemithorax, can occur. Hemostatic agents including antifibrinolytics, desmopressin, fibrinogen concentrates, and other factor concentrates may be needed to achieve hemostasis in these often-challenging patients. Managing bleeding on extracorporeal support requires careful monitoring and a thoughtful approach.

Low antithrombin levels in neonates and infants undergoing congenital heart surgery result in more red blood cell and plasma transfusion on cardiopulmonary bypass.

BACKGROUND: Neonates have lower levels of antithrombin (AT) due to immature liver synthetic function. AT deficiency may lead to inadequate anticoagulation with heparin during cardiac surgery resulting in consumption of coagulation factors and increased blood transfusion. The goal of this study is to examine the effect of AT level on the transfusion requirements of neonates and infants undergoing open heart surgery. STUDY DESIGN AND METHODS: This is a prospective, observational study at a tertiary pediatric referral center. Neonates and infants up to 6 months of age undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were enrolled. Demographic, intraoperative, transfusion, and complications data were collected. Preoperative AT level was measured after induction of anesthesia. Prior to separation from CPB, a second blood sample was drawn and AT, thrombin antithrombin complex (TAT), D-dimer, and anti-Xa levels were measured. Linear and logistic regression were performed for data analysis. RESULTS: Preoperative low AT level was significantly associated with increased transfusion of red blood cells (RBCs) and fresh frozen plasma (FFP) during CPB, but not after separation from CPB. The incidence of thrombosis and re-operation were not associated with preoperative AT levels. There was no association between TAT, D-dimer, and anti-Xa levels at the end of CPB and preoperative AT levels. CONCLUSION: Low preoperative AT level is associated with increased transfusion of RBC and FFP on CPB in neonates and infants undergoing congenital heart surgery. Low preoperative AT level did not result in coagulation activation after CPB and after surgery.

Deep-learning-based single-photon-counting compressive imaging via jointly trained subpixel convolution sampling.

The combination of single-pixel-imaging and single-photon-counting technology can achieve ultrahigh-sensitivity photon-counting imaging. However, its applications in high-resolution and real-time scenarios are limited by the long sampling and reconstruction time. Deep-learning-based compressive sensing provides an effective solution due to its ability to achieve fast and high-quality reconstruction. This paper proposes a sampling and reconstruction integrated neural network for single-photon-counting compressive imaging. To effectively remove the blocking artefact, a subpixel convolutional layer is jointly trained with a deep reconstruction network to imitate compressed sampling. By modifying the forward and backward propagation of the network, the first layer is trained into a binary matrix, which can be applied to the imaging system. An improved deep-reconstruction network based on the traditional Inception network is proposed, and the experimental results show that its reconstruction quality is better than existing deep-learning-based compressive sensing reconstruction algorithms.

Selected 2019 Highlights in Congenital Cardiac Anesthesia.

This article is a review of the highlights of pertinent literature published in 2019, which is of interest to the pediatric cardiac anesthesiologist. After a search of the United States National Library of Medicine PubMed database, several topics emerged in which significant contributions were made in 2019. The authors of this manuscript considered the following topics noteworthy and were included in this review: advances in pediatric heart transplantation, blood management in pediatric cardiac surgery, the impact of nutrition on outcomes in congenital heart surgery, and the use of vasopressin in patients after Fontan palliation.

Inverted Hydration Layers on Bio-Magnesium Surfaces in the Initial Degradation Stage and their Influence on Adsorption of Amino Acid Analogues: The Metadynamics Simulations.

Deeply exploring the interaction of biomolecules with magnesium in solution is essential to understand the formation of complex bio-magnesium interfaces accompanied with corrosion products. Using the accelerated metadynamics simulations, we have investigated the interactions of amino acid analogues on clean and hydroxylated Mg(0001) surfaces by identifying their free energy barriers and adsorption sites. We find that there are two hydration layers stacked on the clean Mg(0001) surfaces and the hydroxylated Mg(0001) surfaces, which mainly determine the free energy barriers and adsorbed configurations. Further studies reveal that the water molecules in double hydration layers present two opposite orientations, depending on the charge distribution of the substrate. Specifically, oxygen atoms of water concentrate in the center of double hydration layers for a clean Mg surface but transfer to the outside surface once the Mg substrate is degraded. The reversed hydration layers greatly reduce the binding affinities of positively charged and electroneutral analogues. Overall, our simulation findings provide new insights into the interaction mechanism of biomolecules on a bio-magnesium device in the implantation initial stage, which is noteworthy for revealing the magnesium degradation mechanism in vivo.

A DFT study of the adsorption of short peptides on Mg and Mg-based alloy surfaces.

Adsorption of short peptides, including three dipeptides: arginine-glycine (Arg-Gly), glycine-aspartic acid (Gly-Asp), arginine-aspartic acid (Arg-Asp), and one tripeptide arginine-glycine-aspartic acid (RGD), on the surfaces of Mg and Mg alloys (Mg-Zn, Mg-Y, and Mg-Nd), was studied using the first-principles calculations based on density functional theory (DFT), considering van der Waals (vdW) correction. The calculated adsorption energies (Eads) of short peptides on the clean Mg(0001) surface are in the range of -1.73 to -2.80 eV per dipeptide, and -3.24 eV for RGD. The short peptides prefer to bond to Mg atoms at the surface by the O and N anions in their functional groups. For the clean Mg(0001) surface, the Eads of the short peptides are exclusively dominated by the number of functional groups binding to the surface. However, for the surface of the Mg-Zn alloy (1% Zn), the adsorption of the peptides is clearly enhanced (by about 0.3 eV per peptide) due to the enhanced N-Mg bond and the electrostatic interactions between the doped Zn at the surface and the backbone chains of the peptides. Furthermore, the attractive interactions are increased with the increase of doped Zn contents (up to 3%). In contrast, for the surfaces of Mg-Y (1% Y) and Mg-Nd (1% Nd) alloys, the adsorption of the peptides is slightly weakened compared to that on the clean Mg(0001) surfaces. Our results provide useful guidance in understanding the interactions between peptides and the Mg-based biomedical alloy surfaces at the atomic scale in the biomimetic coating fields.

Validation of a Mathematical Model of Bidirectional Glenn Circulation With Aortopulmonary Collaterals and the Implications for QP/QS Calculation.

OBJECTIVES: A mathematical model of the oxygen delivery kinetics of the bidirectional Glenn (BDG) shunt circulation incorporating aortopulmonary collateral (APC) flow was created. The model was used to characterize oxygen delivery and compare modeled data to actual patient data obtained using cardiac magnetic resonance imaging (MRI) and catheterization. In addition, cardiac MRI and catheterization assessment of pulmonary blood flow in the presence of APC flow were compared. DESIGN: Mathematical model and retrospective data analysis of patients who underwent cardiac MRI and catheterization. The mathematical model is based on the concept that APC flow to the lungs is recirculated pulmonary venous blood flow, which does not contribute to systemic oxygen delivery. SETTING: Single-center, university teaching hospital. PARTICIPANTS: The study included 98 patients with BDG shunt undergoing cardiac MRI and cardiac catheterization. MEASUREMENTS AND MAIN RESULTS: In the absence of APC flow, the pulmonary blood flow to systemic blood flow ratio (Qp/Qs) calculated using cardiac catheterization data closely matched that obtained with cardiac MRI. In the presence of APC flow, Qp/Qs calculated using cardiac catheterization data systematically underestimated values obtained with cardiac MRI. A mathematical model of BDG shunt oxygen delivery incorporating variable APC flow was created. The model provided reasonable prediction of actual patient data for arterial blood oxygen, superior vena cava oxygen saturation, and oxygen delivery obtained at the time of cardiac catheterization in patients. CONCLUSION: The oxygen delivery kinetics of a BDG shunt incorporating variable APC flow can be modeled mathematically. Model output can be used to predict blood oxygen saturation after coil embolization of APC flow in the cardiac catheterization laboratory.

Preoperative Thromboelastographic Profile of Patients with Congenital Heart Disease: Association of Hypercoagulability and Decreased Heparin Response.

OBJECTIVE: To describe the demographic and thromboelastographic characteristics of patients with congenital heart disease presenting with decreased heparin response before cardiac surgery. DESIGN: Retrospective, observational study. SETTING: Single institution, tertiary, academic, university hospital. PARTICIPANTS: The study comprised 496 pediatric and adult patients undergoing cardiac surgery for congenital heart disease. INTERVENTIONS: Retrospective review of medical records. MEASUREMENTS AND MAIN RESULTS: Data on preoperative thromboelastography (TEG), demographics, and response to heparin were collected retrospectively. Logistic regression analysis was used to study the association between TEG and response to heparin. Decreased heparin response (defined as activated clotting time <480 s initial bolus of 300 U/kg heparin) was observed in 23.6% of patients presenting for surgery. Age distribution and preoperative coagulation profiles were similar for both nonresponders and responders to heparin. Preoperatively, nonresponders demonstrated all thromboelastrographic characteristics consistent with a hypercoagulable profile (shorter reaction time, K value, wider angle, and maximum amplitude). Univariate logistic regression identified all TEG variables significantly associated with decreased heparin response. After adjustment for age, procedure type, and the presence of cyanosis, a multivariate logistic regression model identified the TEG variable K (≤1.3 min) as being significantly associated with decreased heparin response (odds ratio 3.7; confidence interval 2.3-5.8; p < 0.0001). CONCLUSIONS: Decreased response to heparin before cardiac surgery in patients with congenital heart disease is associated with preoperative hypercoagulability identified using a viscoelastic test. Additional studies are needed to better understand the etiology of decreased heparin response and potential clinical strategies to improve anticoagulation management.