The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm.

OBJECTIVES: Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. METHODS: We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. RESULTS: A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (-3.8 days, 95%CI [-5.5; -2.0], P = <.001) and low (-4.0 days, 95% CI [-6.7; -1.2] P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (-4.4 days, 95%CI [-6.4; -2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. CONCLUSION: The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm.

INTRODUCTION: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. MATERIAL AND METHODS: Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. RESULTS: In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P = .002). CONCLUSIONS: This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester

The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm

Objectives Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. Methods We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. Results A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (−3.8 days, 95%CI [−5.5; −2.0], P = <.001) and low (−4.0 days, 95% CI [−6.7; −1.2] P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (−4.4 days, 95%CI [−6.4; −2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. Conclusion The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance

Tris(acetonitrile-&#954;N)dichlorido(triphenylphosphane-&#954;P)ruthenium(II) acetonitrile monosolvate

In the title complex, [RuCl2(CH3CN)3(C18H15P)]&#183;CH3CN, the coordination geometry of the RuII atom is distorted octahedral, defined by one P atom from a triphenylphosphane ligand, three N atoms from three acetonitrile ligands and two Cl atoms. The three acetronitile ligands linearly bind to the RuII atom, with Ru&#8212;N&#8212;C angles of 172.6&#8197;(2), 179.9&#8197;(2) and 171.4&#8197;(2)&#176;

Phase I Study of S-Trans, Trans-Farnesylthiosalicylic Acid (Salirasib), a Novel Oral RAS Inhibitor in Patients With Refractory Hematologic Malignancies

BACKGROUND: RAS/RAF/MAPK activation (mutational or non-mutational) is a key pathway for survival and proliferative advantage of leukemic cells. Salirasib is an oral RAS inhibitor that causes dislocation of RAS by competing directly with farnesylated RAS in binding to its putative membrane binding proteins. Salirasib does not inhibit farnesyl transferase enzyme. METHODS: We report a phase I study of Salirasib in patients with relapsed/refractory hematologic malignancies. Salirasib was administered orally twice daily on days 1–21 of a 28 day cycle in a “3+3” dose escalation design. RESULTS: Seventeen patients with relapsed/refractory leukemia were treated for a median of 4 cycles (range, 1–29). Three patients each were enrolled at dose level of 100, 200, 400, 600 and 800 mg twice daily and 2 pts at dose level of 900 mg twice daily. No dose limiting toxicities were encountered. Grade 1–2 diarrhea has been the only frequent non-hematologic toxicity observed in 14 of 17 (82%) patients and was resolved with oral anti-diarrheal. Eight (47%) pts (4 MDS, 2 AML, 1 CMML, and 1 CML) had hematological improvement; 1 in three lineages, 1 in two lineages, and 6 in one lineage. None of the patient achieved complete remission. The responses lasted for a median of 10 weeks (range, 5–115). Study was discontinued for financial constraints. CONCLUSION: Salirasib was well tolerated and showed modest activity in relapsed/refractory hematological malignancies. The safety profile of Salirasib and its hematological malignancy relevant target makes it a potential drug to be utilized in combination therapy