Maternal and fetal predictors of anthropometry in the first year of life in offspring of women with GDM.

Gestational Diabetes Mellitus (GDM) carries an increased risk for adverse perinatal and longer-term cardiometabolic consequences in offspring. This study evaluated the utility of maternal anthropometric, metabolic and fetal (cord blood) parameters to predict offspring anthropometry up to 1 year in pregnancies with GDM. In this prospective analysis of the MySweetheart study, we included 193/211 women with GDM that were followed up to 1 year postpartum. Maternal predictors included anthropometric (pre-pregnancy BMI, gestational weight gain (GWG), weight and fat mass at the 1 <sup>st</sup> GDM visit), and metabolic parameters (fasting insulin and glucose, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI), HbA1c, triglycerides, and high-density lipoprotein (HDL) at the 1 <sup>st</sup> visit and HbA1c at the end of pregnancy). Fetal predictors (N=46) comprised cord blood glucose and insulin, C-Peptide, HOMA-IR, triglycerides and HDL. Offspring outcomes were anthropometry at birth (weight/weight z-score, BMI, small and large for gestational age (SGA,LGA)), 6-8 weeks and 1 year (weight z-score, BMI/BMI z-score, and the sum of 4 skinfolds). In multivariate analyses, birth anthropometry (weight, weight z-score, BMI and/or LGA), was positively associated with cord blood HDL and HbA1c at the 1 <sup>st</sup> GDM visit, and negatively with maternal QUICKI and HDL at the 1 <sup>st</sup> GDM visit (all p ≤ 0.045). At 6-8 weeks, offspring BMI was positively associated with GWG and cord blood insulin, whereas the sum of skinfolds was negatively associated with HDL at the 1 <sup>st</sup> GDM visit (all p ≤0.023). At 1 year, weight z-score, BMI, BMI z-score, and/or the sum of skinfolds were positively associated with pre-pregnancy BMI, maternal weight, and fat mass at the 1 <sup>st</sup> GDM visit and 3 <sup>rd</sup> trimester HbA1c (all p ≤ 0.043). BMI z-score and/or the sum of skinfolds were negatively associated with cord blood C-peptide, insulin and HOMA-IR (all p ≤0.041). Maternal anthropometric, metabolic, and fetal metabolic parameters independently affected offspring anthropometry during the 1 <sup>st</sup> year of life in an age-dependent manner. These results show the complexity of pathophysiological mechanism for the developing offspring and could represent a base for future personalized follow-up of women with GDM and their offspring

Translating principles of quality control to cardiovascular magnetic resonance: assessing quantitative parameters of the left ventricle in a large cohort

Cardiac magnetic resonance (CMR) examinations require standardization to achieve reproducible results. Therefore, quality control as known as in other industries such as in-vitro diagnostics, could be of essential value. One such method is the statistical detection of long-time drifts of clinically relevant measurements. Starting in 2010, reports from all CMR examinations of a high-volume center were stored in a hospital information system. Quantitative parameters of the left ventricle were analyzed over time with moving averages of different window sizes. Influencing factors on the acquisition and on the downstream analysis were captured. 26,902 patient examinations were exported from the clinical information system. The moving median was compared to predefined tolerance ranges, which revealed an overall of 50 potential quality relevant changes ("alerts") in SV, EDV and LVM. Potential causes such as change of staff, scanner relocation and software changes were found not to be causal of the alerts. No other influencing factors were identified retrospectively. Statistical quality assurance systems based on moving average control charts may provide an important step towards reliability of quantitative CMR. A prospective evaluation is needed for the effective root cause analysis of quality relevant alerts

Myocardial Infarction after Long-Term Treatment with a Tyrosine Kinase Inhibitor (TKI) with Anti-VEGF Receptor Activity

TKIs including anti-VEGF receptor activity have been approved for the treatment of patients with radioiodine resistant thyroid carcinomas. For lenvatinib arterial thromboembolic events are listed as adverse events of special interest with lenvatinib. In the phase III study, arterial thromboembolic events were reported in 3% of lenvatinib-treated patients and 1% in the placebo group. Most of the patients had predisposing factors. Only one myocardial infarct was reported in the lenvatinib phase III study. We report a 73-year-old female patient with metastatic thyroid papillary carcinoma who was treated with total thyroidectomy. The operation was followed by four radioiodine therapies over a period of 6 years. At 6 years she developed lung metastasis without radioiodine uptake, one solitary liver metastasis and one solitary right renal metastasis. One year after the first diagnosis of radioiodine resistant lung metastasis the lung metastasis showed progression according to RECIST criteria. This treatment was resulting in prolonged partial response with disappearance of a hepatic and renal metastasis. A myocardial infarction occurred after 39 months of lenvatinib treatment resulting in implantation of 3 stents and a two chamber pacemaker. The treatment was discontinued. Except for well controlled hypertension there were neither predisposing diseases like diabetes nor symptoms of cardiac ischemia on exertion. However, the family history for cardiovascular diseases was positive for cardiac infarction reported for one brother. Another brother was treated for hypertension and the patient’s mother suffered from a cerebral infarction at the age of 60. While only one myocardial infarct was reported in the lenvatinib phase III study with 392 patients this case suggests that long-term treatment with lenvatinib may be associated with an increased risk for myocardial infarct also in patients with no predisposing diseases except well controlled hypertension and positive family history for cardiovascular diseases.Peer Reviewe

Persistence of the stereochemical activity of the Bi3+ lone electron pair in Bi2Ga4O9 up to 50 GPa and crystal structure of the high-pressure phase

The crystal structure of the high-pressure phase of bismuth gallium oxide, Bi(2)Ga(4)O(9), was determined up to 30.5 (5) GPa from in situ single-crystal in-house and synchrotron X-ray diffraction. Structures were refined at ambient conditions and at pressures of 3.3 (2), 6.2 (3), 8.9 (1) and 14.9 (3) GPa for the low-pressure phase, and at 21.4 (5) and 30.5 (5) GPa for the high-pressure phase. The mode-Grüneisen parameters for the Raman modes of the low-pressure structure and the changes of the modes induced by the phase transition were obtained from Raman spectroscopic measurements. Complementary quantum-mechanical calculations based on density-functional theory were performed between 0 and 50 GPa. The phase transition is driven by a large spontaneous displacement of one O atom from a fully constrained position. The density-functional theory (DFT) model confirmed the persistence of the stereochemical activity of the lone electron pair up to at least 50 GPa in accordance with the crystal structure of the high-pressure phase. While the stereochemical activity of the lone electron pair of Bi(3+) is reduced at increasing pressure, a symmetrization of the bismuth coordination was not observed in this pressure range. This shows an unexpected stability of the localization of the lone electron pair and of its stereochemical activity at high pressure

High-pressure phase transition of Bi2Fe4O9Bi_2Fe_4O_9

The high-pressure behaviour of Bi2Fe4O9 was analysed by in situ powder and single-crystal x-ray diffraction and Raman spectroscopy. Pressures up to 34.3(8) GPa were generated using the diamond anvil cell technique. A reversible phase transition is observed at approximately 6.89(6) GPa and the high-pressure structure is stable up to 26.3(1) GPa. At higher pressures the onset of amorphization is observed. The crystal structures were refined from single-crystal data at ambient pressure and pressures of 4.49(2), 6.46(2), 7.26(2) and 9.4(1) GPa. The high-pressure structure is isotypic to the high-pressure structure of Bi2Ga4O9. The lower phase transition pressure of Bi2Fe4O9 with respect to that of Bi2Ga4O9 (16 GPa) confirms the previously proposed strong influence of cation substitution on the high-pressure stability and the misfit of Ga3+ and Fe3+ in tetrahedral coordination at high pressure. A fit of a second-order Birch–Murnaghan equation of state to the p–V data results in K0 = 74(3) GPa for the low-pressure phase and K0 = 79(2) GPa for the high-pressure phase. The mode Grüneisen parameters were obtained from Raman-spectroscopic measurements