Faculty Bibliography

PURPOSE: To compare the performance of non-contrast MRI with half-Fourier acquisition single-shot turbo spin echo (HASTE) vs. contrast-enhanced MRI/3D-MRCP for assessment of suspected choledocholithiasis in hospitalized patients. METHODS AND MATERIALS: 123 contrast-enhanced abdominal MRI/MRCP scans in the hospital setting for possible choledocholithiasis were retrospectively evaluated. Endoscopic retrograde cholangiopancreatography, intraoperative cholangiogram or documented clinical resolution served as the reference standard. Readers first evaluated the biliary tree using coronal and axial HASTE and other non-contrast sequences, and later reviewed the entire exam with post-contrast sequences and 3D-MRCP. Test performance for the image sets was compared for choledocholithiasis, acute hepatitis, cholangitis, and acute cholecystitis. Reader agreement, MRCP image quality, and confidence levels were also assessed. Clinical predictors of age and fever were tested for association with perceived need for contrast in biliary assessment. RESULTS: There were 27 cases of choledocholithiasis, 31 cases of acute hepatitis, 37 cases of acute cholecystitis, and 3 clinically diagnosed cases of acute cholangitis. Both the abbreviated and full contrast-enhanced/MRCP image sets resulted in high accuracy for choledocholithiasis (91.1-94.3% vs. 91.9-92.7%). There was no difference in sensitivity or specificity for either reader for any diagnosis between image sets (p > 0.40). 1 reader showed improved confidence (p < 0.001) with inclusion of MRCP and contrast-enhanced images, but neither confidence nor MRCP quality scores were associated with diagnostic accuracy. Patient age and fever did not predict the need for contrast-enhanced images. CONCLUSION: In hospitalized patients with suspected choledocholithiasis, performance of non-contrast abdominal MRI with HASTE is similar to contrast-enhanced MRI with 3D-MRCP, offering potential for decreased scanning time and improved patient tolerability.

We assessed the association between urinary metabolites, genetic variants, and incident chronic kidney disease (CKD) in the Framingham Offspring cohort. Among the participants, 193 individuals developed CKD (estimated glomerular filtration rate under 60 ml/min/1.73m²) between cohort examinations 6 (1995-1998) and 8 (2005-2008, mean follow-up 9.7 years). They were age- and sex-matched to 193 control individuals free of CKD. A total of 154 urinary metabolites were measured using mass spectrometry, and the association between metabolites and CKD was examined using logistic regression. Next, we tested the genetic associations of each metabolite with an Illumina exome chip. Urinary glycine and histidine were associated with a lower risk of incident CKD with an odds ratio of 0.59 (95% confidence interval [CI] 0.43-0.80) and 0.65 (0.50-0.85) respectively, per one standard deviation increase in metabolite concentration. Follow-up in the Atherosclerosis Risk in Communities cohort confirmed the association of urinary glycine with CKD. In exome chip analyses, 36 single nucleotide polymorphisms at 30 loci were significantly associated with 31 metabolites. We surveyed exome chip findings for associations with known renal function loci such as rs8101881 in SLC7A9 coding for an amino acid transporter, which has been associated with a lower risk of CKD. We found this polymorphism was significantly associated with higher levels of lysine and NG-monomethyl-L-arginine (NMMA). Increased urinary lysine and NMMA were associated with a lower risk of CKD (0.73 [0.50-0.90] and 0.66 [0.53-0.83], respectively) in the univariate model. Thus, low urinary glycine and histidine are associated with incident CKD. Furthermore, genomic association of urinary metabolomics identified lysine and NMMA as being linked with CKD and provided additional evidence for the association of SLC7A9 with kidney disease.

PURPOSE: Transgender youth are at high risk for mental health morbidities. Based on treatment guidelines, puberty blockers and gender-affirming hormone therapy should be considered to alleviate distress due to discordance between an individual's assigned sex and gender identity. The goals of this study were to examine the: (1) prevalence of mental health diagnoses, self-injurious behaviors, and school victimization and (2) rates of insurance coverage for hormone therapy, among a cohort of transgender adolescents at a large pediatric gender program, to understand access to recommended therapy. METHODS: An IRB-approved retrospective medical record review (2014-2016) was conducted of patients with ICD 9/10 codes for gender dysphoria referred to pediatric endocrinology within a large multidisciplinary gender program. Researchers extracted the following details: demographics, age, assigned sex, identified gender, insurance provider/coverage, mental health diagnoses, self-injurious behavior, and school victimization. RESULTS: Seventy-nine records (51 transgender males, 28 transgender females) met inclusion criteria (median age: 15 years, range: 9-18). Seventy-three subjects (92.4%) were diagnosed with one or more of the following conditions: depression, anxiety, post-traumatic stress disorder, eating disorders, autism spectrum disorder, and bipolar disorder. Fifty-nine (74.7%) reported suicidal ideation, 44 (55.7%) exhibited self-harm, and 24 (30.4%) had one or more suicide attempts. Forty-six (58.2%) subjects reported school victimization. Of the 27 patients prescribed gonadotropin-releasing hormone analogues, only 8 (29.6%) received insurance coverage. CONCLUSION: Transgender youth face significant barriers in accessing appropriate hormone therapy. Given the high rates of mental health concerns, self-injurious behavior, and school victimization among this vulnerable population, healthcare professionals must work alongside policy makers toward insurance coverage reform.

AIMS/HYPOTHESIS:Insulin resistance is frequently associated with hypertension and type 2 diabetes. The cytochrome P450 (CYP) arachidonic acid epoxygenases (CYP2C, CYP2J) and their epoxyeicosatrienoic acid (EET) products lower blood pressure and may also improve glucose homeostasis. However, the direct contribution of endogenous EET production on insulin sensitivity has not been previously investigated. In this study, we tested the hypothesis that endogenous CYP2C-derived EETs alter insulin sensitivity by analysing mice lacking CYP2C44, a major EET producing enzyme, and by testing the association of plasma EETs with insulin sensitivity in humans. METHODS:mice using hyperinsulinaemic-euglycaemic clamps and isolated skeletal muscle. Insulin secretory function was assessed using hyperglycaemic clamps and isolated islets. Vascular function was tested in isolated perfused mesenteric vessels. Insulin sensitivity and secretion were assessed in humans using frequently sampled intravenous glucose tolerance tests and plasma EETs were measured by mass spectrometry. RESULTS:vessels (maximal response 39.3 ± 6.5% of control, p < 0.001), suggesting that impaired vascular reactivity produces impaired insulin sensitivity in vivo. Similarly, plasma EETs positively correlated with insulin sensitivity in human participants. CONCLUSIONS/INTERPRETATION:CYP2C-derived EETs contribute to insulin sensitivity in mice and in humans. Interventions to increase circulating EETs in humans could provide a novel approach to improve insulin sensitivity and treat hypertension.

Personality disorder and personality pathology encompass a dimension of psychological dysfunction known to severely impact multiple domains of functioning. However, there is a notable dearth of research regarding both the pervasiveness and correlates of personality pathology among young sexual minority males who themselves experience heightened mental health burdens. Using the self-report version of the Standardized Assessment of Personality-Abbreviated Scale we tested associations between distinct personality characteristics with sociodemographic and psychosocial factors as well as mental health states in a sample of 528 young (aged 21-25 years) sexual minority men. In multivariate analysis, personality traits varied significantly by race/ethnicity. Personality traits were also positively associated with psychosocial states, specifically, internalized anti-homosexual bias, level of connection with the gay community, and male body dissatisfaction, as well as mental health in the form of recent depressive and anxious symptomatology. These findings support the complex synergy which exists between personality characteristics, psychosocial conditions, and mental health burdens present among sexual minority men and support the need for an all-encompassing approach to both the study and care of this population that addresses the influences of both internal and external factors on well-being.