Browsing by Author "Alazraki, Adina L."

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    Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis
    (Wolters Kluwer, 2021-05-13) Ye, Wen; Leung, Daniel H.; Molleston, Jean P.; Ling, Simon C.; Murray, Karen F.; Nicholas, Jennifer L.; Huang, Suiyuan; Karmazyn, Boaz W.; Harned, Roger K.; Masand, Prakash; Alazraki, Adina L.; Navarro, Oscar M.; Otto, Randolph K.; Palermo, Joseph J.; Towbin, Alexander J.; Alonso, Estella M.; Karnsakul, Wikrom W.; Schwarzenberg, Sarah Jane; Seidel, Glenn F.; Siegel, Marilyn; Magee, John C.; Narkewicz, Michael R.; Freeman, A. Jay; Pediatrics, School of Medicine
    Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7-21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research-grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P < 0.0001), HMG (n = 17, 5.9 kPa [5.2, 7.8]; P = 0.0013), and HTG (n = 18, 6.1 kPa [4.7, 7.0]; P = 0.0008) participants. HMG participants (n = 14) had a significantly higher mean CAP (SD) (270.5 dB/m [61.1]) compared with NL (n = 40, 218.8 dB/m [46.5]; P = 0.0027), HTG (n = 10, 218.1 dB/m [60.7]; P = 0.044), and NOD (n = 15, 222.7 dB/m [56.4]; P = 0.041) participants. LSM had a negative correlation with platelet count (rs = − 0.28, P = 0.0071) and positive correlation with aspartate aminotransferase-to-platelet ratio index (rs = 0.38, P = 0.0002), Fibrosis-4 index (rs = 0.36, P = 0.0007), gamma-glutamyltransferase (GGT; rs = 0.35, P = 0.0017), GGT-to-platelet ratio (rs = 0.35, P = 0.003), and US spleen size z-score (rs = 0.27, P = 0.0073). Conclusion: VCTE is associated with US patterns and conventional markers in patients with liver disease with CF.
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    Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease
    (Oxford University Press, 2021) Ta, Allison D.; Ollberding, Nicholas J.; Karns, Rebekah; Haberman, Yael; Alazraki, Adina L.; Hercules, David; Baldassano, Robert; Markowitz, James; Heyman, Melvin B.; Kim, Sandra; Kirschner, Barbara; Shapiro, Jason M.; Noe, Joshua; Oliva-Hemker, Maria; Otley, Anthony; Pfefferkorn, Marian; Kellermayer, Richard; Snapper, Scott; Rabizadeh, Shervin; Xavier, Ramnik; Dubinsky, Marla; Hyams, Jeffrey; Kugathasan, Subra; Jegga, Anil G.; Dillman, Jonathan R.; Denson, Lee A.; Pediatrics, School of Medicine
    Background: Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. Materials and methods: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq, and the ileal microbial community composition was characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. Results: After controlling for ileal location, baseline ileal LN (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), increasing serum albumin (OR, 4; 95% CI, 1.3-12.3), and anti-Saccharomyces cerevisiae antibodies IgG serology (OR, 0.97; 95% CI, 0.95-1) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (area under the curve, 0.86; positive predictive value, 80%; negative predictive value, 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate-producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and the genus Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, and Aggregatibacter and Blautia bacteria were associated with reduced extracellular matrix gene expression. Conclusions: Pediatric patients with CD with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.