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478 Magnetic Resonance Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease
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- Marissa Brown, Alexander Moody, Juan Vasquez, John Blangero, Luke Norton, Geoffrey Clarke
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 141
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OBJECTIVES/GOALS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern due to its increasing prevalence and association with type 2 diabetes mellitus. Non-invasive magnetic resonance-based biomarkers can aid in the monitoring of disease progression and identification of patients at risk for chronic liver disease. METHODS/STUDY POPULATION: Over 600 subjects will be recruited from the San Antonio Mexican American Family Study and from a second study, which consists of (i) T2DM patients diagnosed with either MASLD or metabolic dysfunction-associated steatohepatitis (MASH) or (ii) metabolically healthy controls. Hydrogen-1 MRS and diffusion-weighted MRI (DW-MRI) will be used to measure liver fat fraction and liver stiffness biomarkers, respectively. Several potential biomarkers of liver stiffness will be evaluated in vivo using the intravoxel incoherent motion (IVIM) model for DW-MRI. To further improve the diagnostic accuracy of patients with liver fibrosis, we will integrate MRI/MRS data with relevant clinical indicators of hepatic metabolism. Results will be compared to biopsy samples to evaluate the model’s diagnostic accuracy. RESULTS/ANTICIPATED RESULTS: Based on preliminary data, we predict that IVIM will be able to accurately diagnose hepatic fibrosis in patients with MASLD, allowing it to be implemented in clinics with high-field MRI units easily. Previous studies have shown correlations between IVIM estimates and fibrosis stages, however, none included additional clinical indicators of liver disease in their models. We have already found significant differences in metabolic measurements such as fasting plasma glucose and HbA1c levels. Additionally, the use of machine learning in developing these models has shown improvements in the ability to extract features from the data. The aim is to achieve high accuracy and robustness in the staging of liver fibrosis. DISCUSSION/SIGNIFICANCE: Over 100 million people in the US are affected by MASLD. Without treatment, it progresses from hepatic steatosis to MASH, fibrosis (liver stiffening), and ultimately to hepatic cirrhosis and hepatocellular carcinoma (HCC). Continued research efforts and clinical implementation of MRI and MRS are vital in combating the growing burden of MASLD.
Dextrose 50% versus Dextrose 10% or Dextrose Titration for the Treatment of Out-of-Hospital Hypoglycemia: A Systematic Review
- Marissa Hurtubise, Jeffery Stirling, Jennifer Greene, Alix JE Carter, Janel Swain, Ryan Brown, Dana Fidgen, Judah P. Goldstein
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- Journal:
- Prehospital and Disaster Medicine / Volume 36 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 04 October 2021, pp. 730-738
- Print publication:
- December 2021
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Introduction:
Paramedics commonly administer intravenous (IV) dextrose to severely hypoglycemic patients. Typically, the treatment provided is a 25g ampule of 50% dextrose (D50). This dose of D50 is meant to ensure a return to consciousness. However, this dose may cause harm and lead to difficulties regulating blood glucose levels (BGLs) post-treatment. It is hypothesized that a lower concentration, such as 10% dextrose (D10), may improve symptoms while minimizing harm.
Methods:PubMed, Embase, CINAHL, and Cochrane Central were systematically searched on September 15, 2020. The PRISMA guidelines were followed. GRADE and risk of bias were applied to determine the certainty of the evidence. Primary literature investigating the use of IV dextrose in hypoglycemic diabetic patients presenting to paramedics or the emergency department was included. Outcomes of interest included safety, efficacy (symptom resolution), and BGL.
Results:Of 680 abstracts screened, 51 full-text articles were reviewed, with eleven studies included. Data from three randomized controlled trials (RCTs) and eight observational studies were analyzed. A single RCT comparing D10 to D50 was identified. The primary significant finding of the study was an increased post-treatment glycemic profile by 3.2mmol/L in the D50 group; no other outcomes had significant differences between groups. When comparing pooled data from all the included studies, there was greater symptom resolution in the D10 group (95.9%) compared to the D50 group (88.8%). However, the mean time to resolution was approximately four minutes longer in the D10 group (4.1 minutes [D50] versus 8.0 minutes [D10]). There was a greater need for subsequent doses with the use of D10 (19.5%) compared to D50 (8.1%). The post-treatment glycemic profile was lower in the D10 group at 6.2mmol/L versus 8.5mmol/L in the D50 group. Both treatments had nearly complete resolution of hypoglycemia: 98.7% (D50) and 99.2% (D10). No adverse events were observed in the D10 group (0/1057) compared to 13/310 adverse events in the D50 group.
Conclusion:Studies show D10 may be as effective as D50 at resolving symptoms and correcting hypoglycemia. Although the desired effect can take several minutes longer, there appear to be fewer adverse events. The post-D10-treatment BGL may result in fewer untoward hyperglycemic episodes.
2187: Investigation of antimicrobial resistance in Ureaplasma species and Mycoplasma hominis isolates from urine cultures in college-aged females
- Marissa Valentine-King, Mary B. Brown
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, p. 25
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OBJECTIVES/SPECIFIC AIMS: Urinary tract infections (UTIs) serve as one of the most common infections affecting women. With rising reports of antibiotic resistance (ABR), which can prolong illness and limit treatment options, the Infectious Disease Society of America recommends using local resistance patterns to shape empirical treatment selection. Although no studies have evaluated ABR in Ureaplasma spp. urinary isolates in college-aged women, regional studies in the Southeast United States have found levels of tetracycline resistance in over 30% of Ureaplasma spp. clinical isolates. Thus, this study aims to determine the antibiogram for 73 Ureaplasma spp. and 10 Mycoplasma hominis isolates collected from women with first-time UTI against a panel of 9 antibiotics, and assess resistant isolates for genetic mechanisms associated with resistance. METHODS/STUDY POPULATION: This study used archival samples and data collected from college-aged women with first-time UTI recruited to participate in a prospective cohort study conducted at a student healthcare facility from 2001 to 2006 in Florida. Ureaplasma spp. and M. hominis isolates cultured from urine samples collected at the initial clinical presentation and for any recurrent UTI were evaluated for susceptibility to a panel of 9 antibiotics (8 for M. hominis) using validated microbroth and agar dilution methods, respectively. Ureaplasma spp. isolates were tested against azithromycin, chloramphenicol, ciprofloxacin, clindamycin, erythromycin, doxycycline, gentamicin, levofloxacin, and tetracycline. M. hominis isolates underwent the same testing, with the addition of linezolid and exclusion of azithromycin and erythromycin, as M. hominis is intrinsically resistance to 14 and 15-membered macrolides and azilides. PCR and Sanger sequencing were employed to identify molecular mechanisms associated with resistance. RESULTS/ANTICIPATED RESULTS: Of the 73 Ureaplasma spp. isolates, 1 isolate was resistant to levofloxacin (MIC: 4 µg/mL) and 1 to tetracycline (MIC: 8 µg/mL). All M. hominis isolates were sensitive. For the Ureaplasma spp. isolates, MIC90s were highest against gentamicin (32 µg/mL) and lowest against doxycycline (0.25 µg/mL). PCR amplification identified tetM present in the tetracycline resistant isolate, an established gene associated with tetracycline resistance in Ureaplasma spp. A S83W mutation within the quinolone-resistance-determining region (QRDR) of parC was detected in the levofloxacin resistant isolate. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, antibiotic resistance in this population of college-aged women with first-time UTI was low. A previous study detected a novel S83W substitution in a perinatal Ureaplasma spp. isolate from Japan, and provided in silico evidence that a S83W change would prevent levofloxacin from binding to its target. However, that study was unable to cultivate the isolate. Our study has provided the corresponding phenotypic evidence that a S83W substitution results in quinolone resistance in Ureaplasma spp.
Glial fibrillary acidic protein in children with congenital heart disease undergoing cardiopulmonary bypass
- Marissa A. Brunetti, Jacky M. Jennings, R. Blaine Easley, Melania Bembea, Anna Brown, Eugenie Heitmiller, Jamie M. Schwartz, Ken M. Brady, Luca A. Vricella, Allen D. Everett
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- Journal:
- Cardiology in the Young / Volume 24 / Issue 4 / August 2014
- Published online by Cambridge University Press:
- 11 July 2013, pp. 623-631
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Objective: To determine whether blood levels of the brain-specific biomarker glial fibrillary acidic protein rise during cardiopulmonary bypass for repair of congenital heart disease. Methods: This is a prospective observational pilot study to characterise the blood levels of glial fibrillary acidic protein during bypass. Children <21 years of age undergoing bypass for congenital heart disease at Johns Hopkins Hospital and Texas Children's Hospital were enrolled. Blood samples were collected during four phases: pre-bypass, cooling, re-warming, and post-bypass. Results: A total of 85 patients were enrolled between October, 2010 and May, 2011. The median age was 0.73 years (range 0.01–17). The median weight was 7.14 kilograms (range 2.2–86.5). Single ventricle anatomy was present in 18 patients (22%). Median glial fibrillary acidic protein values by phase were: pre-bypass: 0 ng/ml (range 0–0.35); cooling: 0.039 (0–0.68); re-warming: 0.165 (0–2.29); and post-bypass: 0.112 (0–0.97). There were significant elevations from pre-bypass to all subsequent stages, with the greatest increase during re-warming (p = 0.0001). Maximal levels were significantly related to younger age (p = 0.03), bypass time (p = 0.03), cross-clamp time (p = 0.047), and temperature nadir (0.04). Peak levels did not vary significantly in those with single ventricle anatomy versus two ventricle repairs. Conclusion: There are significant increases in glial fibrillary acidic protein levels in children undergoing cardiopulmonary bypass for repair of congenital heart disease. The highest values were seen during the re-warming phase. Elevations are significantly associated with younger age, bypass and cross-clamp times, and temperature nadir. Owing to the fact that glial fibrillary acidic protein is the most brain-specific biomarker identified to date, it may act as a rapid diagnostic marker of brain injury during cardiac surgery.