Cerebrovascular Autoregulation in Preterm Infants During and After Surgical Ligation of the Ductus Arteriosus, a Comparison Between Two Surgical Approaches

Objective: During ligation of the ductus arteriosus, cerebrovascular autoregulation (CAR) may deteriorate. It is unknown whether different surgical approaches affect changes in CAR differently. The objective of this study was to compare the potential change in CAR in preterm infants during and after ligation comparing two surgical approaches: sternotomy and posterolateral thoracotomy. Design: This was an observational cohort pilot study. Setting: Level III NICU. Patients: Preterm infants (GA < 32 weeks) requiring ductal ligation were eligible for inclusion. Interventions: Halfway the study period, our standard surgical approach changed from a posterolateral thoracotomy to sternotomy. We analyzed dynamic CAR, using an index of autoregulation (COx) correlating cerebral tissue oxygen saturation and invasive arterial blood pressure measurements, before, during, and after ligation, in relation to the two approaches. Measurements and Main Results: Of nine infants, four were approached by thoracotomy and five by sternotomy. Median GA was 26 (range: 24.9–27.9) weeks, median birth weight (BW) was 800 (640–960) grams, and median post-natal age (PNA) was 18 (15–30) days, without differences between groups. COx worsened significantly more during and after thoracotomy from baseline (Δρ from baseline: during surgery: Δ + 0.32, at 4 h: Δ + 0.36, at 8 h: Δ + 0.32, at 12 h: Δ + 0.31) as compared with sternotomy patients (Δρ from baseline: during surgery: Δ + 0.20, at 4 h: Δ + 0.05, at 8 h: Δ + 0.15, at 12 h: Δ + 0.11) (F = 6.50; p = 0.038). Conclusions: In preterm infants, CAR reduced significantly during and up to 12 h after ductal ligation in all infants, but more evident during and after posterolateral thoracotomy as compared with sternotomy. These results need to be confirmed in a larger population

Involutory reflection groups and their models

AbstractA finite subgroup G of GL(n,C) is involutory if the sum of the dimensions of its irreducible complex representations is given by the number of absolute involutions in the group, i.e. elements g∈G such that gg¯=1, where the bar denotes complex conjugation. A uniform combinatorial model is constructed for all non-exceptional irreducible complex reflection groups which are involutory including, in particular, all infinite families of finite irreducible Coxeter groups

Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization

OBJECTIVE: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. METHODS: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors. RESULTS: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis-SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03-1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01-1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (β = 0.24 [95% CI 0.02-0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04-1.15]), but otherwise had attenuated effects. CONCLUSION: This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Volume Expansion Does Not Alter Cerebral Tissue Oxygen Extraction in Preterm Infants with Clinical Signs of Poor Perfusion

<p>Background: Preterm infants with signs of poor perfusion are often treated with volume expansion, although evidence regarding its effect on cerebral perfusion is lacking. Moreover, the effect is questionable in preterm infants with an adequate cerebrovascular autoregulation (CAR). A useful measure to assess perfusion is cerebral fractional tissue oxygen extraction (cFTOE). Objectives: To assess the effect of volume expansion on cFTOE in preterm infants with signs of poor perfusion. Methods: In this observational study, we assessed cFTOE using near-infrared spectroscopy in preterm infants with signs of poor perfusion before, during and 1 h after volume expansion treatment. Simultaneously, we measured mean arterial blood pressure (MABP). We tested the effect of volume expansion on both cFTOE and MABP, using multi-level analyses. We intended to define a subgroup that responded to volume expansion with an increase in blood pressure and a decrease in cFTOE, suggesting absent CAR. Results: In 14 preterm infants, with a median gestational age of 26.7 weeks (25.0-28.7 weeks) and a median birth weight of 836 g (615-1,290 g), we found a small increase in MABP during (1.4 +/- 1.4 mm Hg, p = 0.003) and after (1.8 +/- 1.7 mm Hg, p = 0.001) volume expansion, but no change in cFTOE during (-0.19 +/- 0.1% p = 0.44) or after (-0.53 +/- 0.1% p = 0.34) volume expansion. We were unable to define a subgroup lacking CAR. Conclusions: Cerebral perfusion, as assessed by cFTOE, does not improve in preterm infants with signs of poor perfusion following volume expansion. In these infants, either CAR is present or volume expansion is inadequate to affect cFTOE. Copyright (C) 2013 S. Karger AG, Basel</p>

Cerebral oxygen saturation during the first 72h after birth in infants diagnosed prenatally with congenital heart disease

BACKGROUND: Evidence suggests that hypoxic-ischemic brain injury in infants with congenital heart disease already occurs during early life. The aim of our study was, therefore, to assess the course of regional cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) during the first 72h after birth in infants with prenatally diagnosed duct-dependent congenital heart disease. In addition, we identified clinical parameters that were associated with rcSO2. MATERIALS AND METHODS: We included 56 infants with duct-dependent congenital heart disease. We measured arterial oxygen saturation (SpO2) and rcSO2 during the first 72h after birth. Simultaneously, we calculated FTOE. RESULTS: We observed median rcSO2 values of approximately 60%, a decreasing FTOE from 0.34 on day 1 to 0.28 on day 3 and stable preductal SpO2 values around 90%. Several clinical variables were associated with rcSO2. In a multiple linear regression model only type of CHD and preductal SpO2 were significant predictors of rcSO2 during the first three days after birth. Infants with a duct-dependent pulmonary circulation had up to 12% lower rcSO2 values than infants with a duct-dependent systemic circulation. CONCLUSION: We demonstrated that, during the first three days after birth, cerebral oxygen saturation is low in infants with duct-dependent congenital heart disease. Furthermore, this study provides preoperative reference values of rcSO2 and FTOE in infants with duct-dependent CHD

The Association between Multisite Near-Infrared Spectroscopy and Routine Hemodynamic Measurements in Relation to Short-Term Outcome in Preterms with Clinical Sepsis

BACKGROUND: The added clinical value of multisite near-infrared spectroscopy (NIRS) monitoring to detect low organ tissue perfusion in preterm infants at risk of circulatory failure remains unclear. OBJECTIVES: To evaluate the associations between multisite NIRS measurements and clinical signs of circulatory failure in relation to short-term outcome in preterm infants with clinical sepsis. METHODS: Prospective cohort study of preterm infants (gestational age <32 weeks) with clinical sepsis. We monitored cerebral, renal, and intestinal oxygen saturation using NIRS for 72 h following sepsis workup and calculated fractional tissue oxygen extraction (FTOE). We recorded clinical signs of circulatory failure every 8 h. We analyzed the associations between FTOE values, clinical signs of circulatory failure, and short-term outcome. RESULTS: In 28 preterm infants with clinical sepsis, intraindividual and interindividual associations between NIRS values and clinical signs of circulatory failure were weak. At several points of time during the study period, cerebral and renal FTOE were higher in infants who developed intestinal complications compared with infants who did not, while clinical signs of circulatory failure never differed between groups. After correcting for multiple testing, significant differences disappeared. CONCLUSIONS: The associations between multisite FTOE values and clinical signs of circulatory failure were weak in preterm infants with clinical sepsis. Nevertheless, in contrast to clinical signs of circulatory failure, cerebral and renal FTOE values were associated with adverse short-term intestinal outcome in the uncorrected analyses. Multisite NIRS monitoring might help to detect critically low tissue oxygen delivery leading to adverse intestinal outcome not detected by routine hemodynamic measurements