Development of a composite diffusion tensor imaging score correlating with short-term neurological status in neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

Association of Cerebral Oximetry with Outcomes after Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is associated with neurologic morbidity and mortality. We investigated whether cerebral regional oxygen saturation (rSO2) is associated with neurologic outcomes and survival in children on ECMO. METHODS: This was a retrospective observational study of children aged 1 day to 20 years who underwent ECMO with routine cerebral rSO2 monitoring in the pediatric intensive care unit at a single academic center between February 2008 and September 2014. We collected all serial rSO2 values recorded in the electronic medical record during the ECMO course. Favorable outcome was defined as survival with Pediatric Cerebral Performance Category (PCPC) ≤ 2 at hospital discharge or no decline from baseline PCPC. RESULTS: We reviewed data from 153 patients who underwent 156 ECMO runs. The median age was 12.5 days (interquartile range [IQR], 2 days-15 months). Ninety-nine (64%) patients survived to hospital discharge, and 82/99 (83%) survivors had favorable neurologic outcome by discharge PCPC. Neuroimaging studies were obtained in 135 (87%) patients, 59 (44%) of which showed abnormal findings. Ninety-two (59%) patients had any rSO2 ≤ 50%, 60 (38%) had any rSO2 decline > 20% from baseline, and 26 (17%) had any rSO2 decline > 20% from the reading 1 h prior. Any rSO2 ≤ 50% and any rSO2 decline > 20% from baseline were each associated with unfavorable outcome at hospital discharge (multivariable-adjusted odds ratio [OR], 2.82 [95% CI 1.10-7.25] and 4.52 [95% CI 1.76-11.58], respectively). rSO2 decline > 20% from the reading 1 h prior was not significantly associated with the outcomes. CONCLUSION: Among children in one institution who underwent routine clinical rSO2 monitoring during ECMO, rSO2 decline was associated with unfavorable short-term neurologic outcome and death after adjusting for potential confounders. The effectiveness of initiating early preventative measures in these high-risk patients needs further study.

Association Between Statin Use and Sex Hormone in the Multi-Ethnic Study of Atherosclerosis Cohort.

PURPOSE: Based on the 2018 American College of Cardiology/American Heart Association cholesterol guidelines, the number of individuals eligible for statin therapy to reduce atherosclerotic cardiovascular disease risk has greatly expanded. Statins inhibit cholesterol biosynthesis, which can impair gonadal steroidogenesis. We evaluated the effect of statins on endogenous sex hormones in a large epidemiological study. METHODS: A total of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants underwent the baseline examination. Of these, 6171 had measurements of serum sex hormones available: dehydroepiandrosterone (DHEA), SHBG, estradiol, and total and bioavailable testosterone. Multivariable linear regression models were used to assess the relationship of statin use with each sex hormone. RESULTS: A total of 345 women (17.4%) and 464 men (14.7%) were statin users (mean age, 67 years; 41% white, 29% black, 11% Chinese, and 19% Hispanic). Among the users vs nonusers of statins, the mean SHBG was 3.54 nmol/L (P < 0.01) lower in women and 3.37 nmol/L (P < 0.001) lower in men; the mean DHEA was 1.06 nmol/L (P < 0.05) lower in women and 0.70 nmol/L (P < 0.01) lower in men, after adjustment for potential confounders. With further propensity score adjustment, the mean DHEA and SHBG levels were 0.67 nmol/L (P < 0.05) and 3.49 nmol/L (P < 0.001) lower, respectively, for statin users vs nonusers. No statistically significant association was noted between estradiol, total testosterone, and bioavailable testosterone and statin use. CONCLUSION: Statin users have lower levels of SHBG and DHEA. This is especially relevant owing to the increasing use of statin therapy.