Publications by authors named "Beverley Huet"

7 Publications

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Routine Neuroimaging: Understanding Brain Injury in Pediatric Extracorporeal Membrane Oxygenation.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Pediatric Critical Care, Pediatrix Medical Group, Orem, UT. Department of Population and Data Science, University of Texas Southwestern Medical Center, Dallas, TX. Children's Medical Center, Dallas, TX. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX.

Objectives: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury.

Design: Retrospective observational single-center cohort study.

Setting: Tertiary care PICU.

Patients: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI.

Interventions: Extracorporeal membrane oxygenation support.

Measurements And Main Results: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence.

Conclusions: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.
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http://dx.doi.org/10.1097/CCM.0000000000005308DOI Listing
September 2021

Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation.

Pediatr Crit Care Med 2020 10;21(10):879-885

Children's Health in Dallas, Dallas, TX.

Objectives: To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation.

Design: A retrospective cohort study.

Setting: Tertiary PICU.

Patients: Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018.

Measurements And Main Results: Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group.

Conclusions: This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.
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http://dx.doi.org/10.1097/PCC.0000000000002438DOI Listing
October 2020

Changes to trimethylamine-N-oxide and its precursors in nascent metabolic syndrome.

Horm Mol Biol Clin Investig 2018 Apr 18;35(2). Epub 2018 Apr 18.

California Northstate University, College of Medicine, 9700 Taron Drive, Elk Grove, CA 95757, USA.

Background Metabolic syndrome (MetS), a cardio-metabolic cluster afflicting 35% of American adults, increases cardiovascular disease (CVD) and type-2 diabetes (T2DM) risk. Increased levels of trimethylamine N-oxide (TMAO), a metabolite derived from choline and L-carnitine, correlates with CVD and T2DM. However, the precise role of TMAO and its precursors in MetS remains unclear. We tested the hypothesis that choline, L-carnitine and TMAO in MetS patients without CVD or T2DM would be altered and correlate with inflammatory markers. Materials and methods This was an exploratory study of 30 patients with nascent MetS (without CVD or T2DM) and 20 matched controls. MetS was defined by the Adult Treatment Panel III criteria. TMAO and its precursors were evaluated from each patient's frozen early morning urine samples and quantified using liquid chromatography/mass spectrometry (LC-MS). These amines were correlated with a detailed repertoire of biomarkers of inflammation and adipokines. Results L-carnitine was significantly increased (p = 0.0002) compared to controls. There was a trend for a significant increase in TMAO levels (p = 0.08). Choline was not significantly altered in MetS. L-carnitine correlated significantly with soluble tumor necrosis factor 1 (sTNFR1) and leptin, and inversely to adiponectin. TMAO correlated with IL-6, endotoxin and chemerin. Neither choline, nor L-carnitine significantly correlated with TMAO. Conclusion L-carnitine is directly correlated with markers of inflammation in nascent MetS. Cellular L-carnitine could be a biomediator or marker of inflammation in the pathogenesis of MetS, and the sequelae of CVD and T2DM.
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http://dx.doi.org/10.1515/hmbci-2018-0015DOI Listing
April 2018

Defining variation in urinary oxalate in hyperoxaluric stone formers.

J Endourol 2013 Dec 22;27(12):1530-4. Epub 2013 Oct 22.

1 Department of Urology, University of Texas Southwestern Medical Center , Dallas, Texas.

Background And Purpose: The development of effective preventive therapy for renal calculi in patients with secondary hyperoxaluria (2°HO) relies on establishing the pattern of normal variation in urinary oxalate (uOx) and attempting to reduce it. Therefore, we evaluated uOx at baseline and at subsequent time points in stone formers with 2°HO.

Methods: We reviewed the charts of 201 recurrent stone formers with 2°HO (uOx ≥ 40 mg/day). The 24-hour urine collections at baseline and after initiation of clinician-directed therapies were analyzed. Mixed models were constructed to analyze uOx over time for individual patients and as a group. Subgroup analyses were performed for enteric and idiopathic 2°HO. Coefficients of variation were computed using the root mean square error from linear models.

Results: The etiology of 2°HO was enteric in 17.9% and idiopathic in 82.1% of patients. Among the 943 urine collections analyzed, 196 oxalate values were derived from the enteric group and 747 from the idiopathic group. The median number of uOx values measured per person was four. The median 24-hour uOx (mg/day) was significantly higher for the enteric group than for the idiopathic group at the time of diagnosis: 64.4 (interquartile range [IQR]=48-90) vs 46.0 (IQR=38-56), P<0.001) and during follow-up (58.2 [IQR=46-86] vs 44.2 [IQR=35-53], P<0.001). Over a median follow-up of 22.5 months, 44.4% of the enteric and 61.8% of the idiopathic patients had at least one normal uOx value (P=0.06). The coefficients of variation for the enteric and idiopathic groups were 40.8% and 27.3%, respectively, with variation randomly displayed in either direction for both groups.

Conclusions: Among patients with 2°HO, uOx demonstrates significant random variation over time even with the incorporation of standard treatments, with enteric HO demonstrating higher values and greater variance than idiopathic HO.
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http://dx.doi.org/10.1089/end.2013.0199DOI Listing
December 2013

Increased toll-like receptor activity in patients with metabolic syndrome.

Diabetes Care 2012 Apr 22;35(4):900-4. Epub 2012 Feb 22.

Laboratory of Atherosclerosis and Metabolic Research, University of California Davis Medical Center, Sacramento, California, USA.

Objective: The metabolic syndrome (MetS) is highly prevalent and confers an increased risk for diabetes and cardiovascular disease (CVD). While MetS is a proinflammatory state, there is a paucity of data on cellular inflammation in MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of the innate immune response.

Research Design And Methods: The aim of this study was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD and control subjects since both of the receptors have been implicated in atherosclerosis and insulin resistance. Fasting blood was obtained for TLR expression and activity.

Results: Circulating levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and soluble tumor necrosis factor receptor 1 (sTNFR1) were significantly increased in MetS versus control subjects following adjustment for waist circumference. There was a significant increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after adjustment for waist circumference. In addition to increased nuclear factor-κB nuclear binding, there was significantly increased release of IL-1β, IL-6, and IL-8 in MetS versus control subjects following priming of the monocytes with lipopolysaccharides. While both plasma free fatty acids and endotoxin were increased in MetS, they correlated significantly with TLR4 only.

Conclusions: In conclusion, we make the novel observation that both TLR2 and TLR4 expression and activity are increased in the monocytes of patients with MetS and could contribute to increased risk for diabetes and CVD.
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http://dx.doi.org/10.2337/dc11-2375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308307PMC
April 2012

Adiposity-independent sympathetic activity in black men.

J Appl Physiol (1985) 2010 Jun 18;108(6):1613-8. Epub 2010 Mar 18.

Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., U9.400, Dallas, TX 75390-8586, USA.

Obesity is thought to lead to sympathetic overactivity as a compensatory adjustment to weight gain. However, most of the experimental support for the hypothesis has been derived from white cohorts. Our previous study in blacks indicated that sympathetic nerve activity (SNA) is closely correlated with body mass index only in women, whereas, in black men, SNA is elevated and dissociated from adiposity (Abate et al., Hypertension 38: 379-383, 2001). To further determine whether total and regional adiposity are determinants of SNA in blacks, we performed a prospective weight loss study in 12 normotensive obese black men and 9 obese black women. SNA, body mass index, and abdominal fat mass were measured before and 16 wk after hypocaloric diet. The major new findings are that, in obese black men, the dietary-induced weight loss of 11.3+/-0.8 kg resulted in reduction in plasma leptin, insulin, and visceral abdominal fat but had no effect on SNA (from baseline of 26+/-4 to 28+/-3 bursts/min, P=not significant). In contrast, in black women, weight loss of 8.0+/-0.9 kg caused similar reductions in plasma leptin, insulin, and visceral abdominal fat and led to a reduction in SNA by 40% (from baseline of 22+/-2 to 13+/-3 bursts/min, P<0.05). In conclusion, these new data from this prospective study provide strong support for a major adiposity-independent sympathetic activity in black men and adiposity-related sympathetic activity in black women.
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http://dx.doi.org/10.1152/japplphysiol.00058.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886690PMC
June 2010

Effect of ascorbic acid consumption on urinary stone risk factors.

J Urol 2003 Aug;170(2 Pt 1):397-401

Department of Urology, The University of Texas Southwestern Medical Center, Dallas, 75390-9110, USA.

Purpose: Ascorbic acid (AA) has been implicated as a risk factor for calcium oxalate stones due to its conversion to oxalate and potential acidifying properties. We evaluated the effect of AA consumption on urinary saturation of calcium oxalate (CaOx) and urinary pH.

Materials And Methods: A total of 12 normal subjects (NS) and 12 CaOx stone formers (SF) underwent 2, 6-day phases of study while maintained on a controlled metabolic diet. In each phase subjects ingested 1 gm AA or an identical appearing placebo twice daily. On the last 2 days of each phase 2, 24-hour urine collections were analyzed for pH and stone risk factors, and blood specimens were submitted for serum chemistry studies.

Results: No difference in urinary pH was found between placebo and AA phases in NS (6.02 versus 6.02) and SF (6.0 versus 6.0). However, urinary oxalate was statistically significantly higher in the AA versus placebo phase for NS (34.7 versus 28.5 mg, p = 0.008) and SF (41.0 versus 30.5 mg, p <0.001). Likewise, the CaOx relative saturation ratio was significantly higher in the AA versus placebo phase for both groups.

Conclusions: Ingestion of 2 gm AA daily results in no change in urinary pH but a moderate though statistically significant increase in urinary oxalate in NS (20%) and SF (33%). Stone formers respond no differently to AA than normal subjects. We recommend limiting AA use to less than 2 gm daily in CaOx stone formers.
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http://dx.doi.org/10.1097/01.ju.0000076001.21606.53DOI Listing
August 2003
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