Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors.

BACKGROUND: While dysregulated sphingolipid metabolism has been associated with risk of childhood asthma, the specific sphingolipid classes and/or mechanisms driving this relationship remain unclear. We aimed to understand the multifaceted role between sphingolipids and other established asthma risk factors that complicate this relationship. METHODS: We performed targeted LC-MS/MS-based quantification of 77 sphingolipids in plasma from 997 children aged 6 years from two independent cohorts (VDAART and COPSAC2010 ). We examined associations of circulatory sphingolipids with childhood asthma, lung function, and three asthma risk factors: functional SNPs in ORMDL3, low vitamin D levels, and reduced gut microbial maturity. Given racial differences between these cohorts, association analyses were performed separately and then meta-analyzed together. RESULTS: We observed elevations in circulatory sphingolipids with asthma phenotypes and risk factors; however, there were differential associations of sphingolipid classes with clinical outcomes and/or risk factors. While elevations from metabolites involved in ceramide recycling and catabolic pathways were associated with asthma and worse lung function [meta p-value range: 1.863E-04 to 2.24E-3], increased ceramide levels were associated with asthma risk factors [meta p-value range: 7.75E-5 to .013], but not asthma. Further investigation identified that some ceramides acted as mediators while some interacted with risk factors in the associations with asthma outcomes. CONCLUSION: This study demonstrates the differential role that sphingolipid subclasses may play in asthma and its risk factors. While overall elevations in sphingolipids appeared to be deleterious overall; elevations in ceramides were uniquely associated with increases in asthma risk factors only; while elevations in asthma phenotypes were associated with recycling sphingolipids. Modification of asthma risk factors may play an important role in regulating sphingolipid homeostasis via ceramides to affect asthma. Further function work may validate the observed associations.

The relationship of fetal sex and maternal race and ethnicity with early and late pregnancy C-reactive protein and interleukin-8.

PROBLEM: Promotion of a healthy pregnancy is dependent on a coordinated immune response that minimizes inflammation at the maternal-fetal interface. Few studies investigated the effect of fetal sex on proinflammatory biomarkers during pregnancy and whether maternal race could impact this association. We aimed to examine whether fetal sex could, independently of maternal race/ethnicity and the condition of pregnancy (normal vs. complicated), impact inflammatory markers (C-reactive protein [CRP] and interleukin-8 [IL-8] levels) in early and late pregnancy. METHODS OF STUDY: This study was a cohort analysis using prospectively collected data from pregnant women who participated in the Vitamin Antenatal Asthma Reduction Trial (VDAART, N = 816). Maternal serum CRP and IL-8 levels were measured in early and late pregnancy (10-18 and 32-38 weeks of gestation, respectively). Five hundred and twenty-eight out of 816 pregnant women who participated in the trial had available CRP and IL-8 measurements at both study time points. We examined the association of fetal sex with early and late CRP and IL-8 levels and their paired sample difference. We further investigated whether maternal race/ethnicity, pregnancy complications (i.e., preeclampsia and gestational diabetes), and early pregnancy body mass index (BMI) could affect the association between these two biomarkers and fetal sex adjusting for potential confounders. For this purpose, we used generalized linear and logistic regression models on log-normalized early and late CRP and IL-8 levels as well as their split at median to form high and low groups. RESULTS: Women pregnant with male fetuses (266/528 = 56.5%) had higher CRP levels in early to mid-pregnancy (ß = .18: 95% confidence interval [CI]: CI = 0.03-0.32; p = .02). Twenty-seven percent (143/528) of the study subjects were Hispanic. Hispanic African American [AA] women and women of races other than White and AA had higher levels of CRP at early to mid-pregnancy compared with White women (ß = .57; 95% CI: 0.17-0.97; p < .01 and ß = .27; 95% CI: 0.05-0.48; p = .02, respectively). IL-8 levels were not associated with fetal sex in early and late pregnancy (p's > .05). Other factors such as gestational diabetes and early pregnancy BMI were associated with higher CRP levels and higher CRP and IL-8 levels, respectively. Dichotomizing log-normalized cytokine levels at the median in a sensitivity analysis, women with male fetuses had lower odds of high (above-median) IL-8 levels at early pregnancy. Also, women with races other than AA and White carrying male fetuses had higher odds of having high (above-median) late-pregnancy CRP and early-pregnancy IL-8 levels (adjusted odds ratio [aOR] = 3.80, 95% CI: 0.24-1.23; p = .02 and aOR = 3.57; 95% CI: 0.23-1.03; p = .02, respectively). Of the pregnancy complications, women with gestational diabetes mellitus had a higher paired difference of early and late pregnancy CRP levels (ß = .38; 95% CI: 0.09-0.68; p = .01), but no difference in IL-8 levels (p's > .05). No associations between the inflammatory markers and preeclampsia were found. CONCLUSION: Fetal sex is associated with CRP in early pregnancy and an association with IL-8 in early pregnancy is implied. Our study further indicates that maternal race/ethnicity could be a contributing factor in the relationship between fetal sex and inflammatory responses during pregnancy. However, the specificity and level of the contribution might vary by type of cytokine, pregnancy stage, and other confounding factors such as BMI that may impact these associations.

Environmental and genetic associations with aberrant early-life gut microbial maturation in childhood asthma.

BACKGROUND: Environmental, genetic, and microbial factors are independently associated with childhood asthma. OBJECTIVE: We sought to determine the roles of environmental exposures and 17q12-21 locus genotype in the maturation of the early-life microbiome in childhood asthma. METHODS: We analyzed fecal 16s rRNA sequencing at age 3 to 6 months and age 1 year to characterize microbial maturation of offspring of participants in the Vitamin D Antenatal Reduction Trial. We determined associations of microbial maturation and environmental exposures in the mediation of asthma risk at age 3 years. We examined 17q12-21 genotype and microbial maturation associations with asthma risk in Vitamin D Antenatal Reduction Trial and the replication cohort Copenhagen Prospective Studies on Childhood Asthma 2010. RESULTS: Accelerated fecal microbial maturation at age 3 to 6 months and delayed maturation at age 1 year were associated with asthma (P < .001). Fecal Bacteroides was reduced at age 3 to 6 months in association with subsequent asthma (P = .006) and among subjects with lower microbial maturation at age 1 year (q = 0.009). Sixty-one percent of the association between breast-feeding and asthma was mediated by microbial maturation at age 3 to 6 months. Microbial maturation and 17q12-21 genotypes exhibited independent, additive effects on childhood asthma risk. CONCLUSIONS: The intestinal microbiome and its maturation mediates associations between environmental exposures including breast-feeding and asthma. The intestinal microbiome and 17q12-21 genotype appear to exert additive and independent effects on childhood asthma risk.

Early-life fecal metabolomics of food allergy.

BACKGROUND: Intestinal microenvironmental perturbations may increase food allergy risk. We hypothesize that children with clinical food allergy, those with food sensitization, and healthy children can be differentiated by intestinal metabolites in the first years of life. METHODS: In this ancillary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we performed untargeted metabolomic profiling in 824 stool samples collected at ages 3-6 months, 1 year and 3 years. Subjects included 23 with clinical food allergy at age 3 and/or 6 years, 151 with food sensitization but no clinical food allergy, and 220 controls. We identified modules of correlated, functionally related metabolites and sought associations of metabolite modules and individual metabolites with food allergy/sensitization using regression models. RESULTS: Several modules of functionally related intestinal metabolites were reduced among subjects with food allergy, including bile acids at ages 3-6 months and 1 year, amino acids at age 3-6 months, steroid hormones at 1 year, and sphingolipids at age 3 years. One module primarily containing diacylglycerols was increased in those with food allergy at age 3-6 months. Fecal caffeine metabolites at age 3-6 months, likely derived from breast milk, were increased in those with food allergy and/or sensitization (beta = 5.9, 95% CI 1.0-10.8, p = .02) and were inversely correlated with fecal bile acids and bilirubin metabolites, though maternal plasma caffeine levels were not associated with food allergy and/or sensitization. CONCLUSIONS: Several classes of bioactive fecal metabolites are associated with food allergy and/or sensitization including bile acids, steroid hormones, sphingolipids, and caffeine metabolites.

The maternal prenatal and offspring early-life gut microbiome of childhood asthma phenotypes.

BACKGROUND: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. METHODS: Our objective was to identify associations between features of the prenatal and early-life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (n = 120) and offspring at ages 3-6 months (n = 265), 1 (n = 436) and 3 years (n = 506) in a total of 657 mother-child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate-adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. RESULTS: Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p = .03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. CONCLUSION: Overall, our results suggest that the early-life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years.

Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study.

Maternal infection and stress during the prenatal period have been associated with adverse neurodevelopmental outcomes in offspring, suggesting that biomarkers of increased inflammation in the mothers may associate with poorer developmental outcomes. In 491 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we investigated the association between maternal levels of two inflammatory biomarkers; interleukin-8 (IL-8) and C-Reactive Protein (CRP) during early (10-18 wks) and late (32-38 wks) pregnancy with offspring scores in the five domains of the Ages and Stages Questionnaire, a validated screening tool for assessing early life development. We identified a robust association between early pregnancy IL-8 levels and decreased fine-motor (ß: -0.919, 95%CI: -1.425, -0.414, p = 3.9 × 10-4) and problem-solving skills at age two (ß: -1.221, 95%CI: -1.904, -0.414, p = 4.9 × 10-4). Associations between IL-8 with other domains of development and those for CRP did not survive correction for multiple testing. Similarly, while there was some evidence that the detrimental effects of early pregnancy IL-8 were strongest in boys and in those who were not breastfed, these interactions were not robust to correction for multiple testing. However, further research is required to determine if other maternal inflammatory biomarkers associate with offspring neurodevelopment and work should continue to focus on the management of factors leading to increases in IL-8 levels in pregnant women.

The Association of Prenatal C-Reactive Protein and Interleukin-8 Levels with Maternal Characteristics and Preterm Birth.

OBJECTIVE: The determinants of preterm birth remain unknown. Excessive maternal inflammation during pregnancy may play an important role in the pathogenesis of preterm birth. Our objective was to describe the association of prenatal levels of proinflammatory C-reactive protein (CRP) and interleukin-8 (IL-8) with preterm birth in participants of the Vitamin D Antenatal Asthma Reduction Trial. STUDY DESIGN: Five hundred and twenty-eight patients with available samples of both first- and third-trimester plasma were included in this analysis. CRP and IL-8 were measured from maternal prenatal samples. We examined the association between prenatal CRP and IL-8 with maternal health characteristics and the outcome of preterm birth. We also described the patterns of change in CRP and IL-8 from first to third trimester and their association with preterm birth. A subgroup analysis comparing only those with a spontaneous preterm birth phenotype to those with term birth was also performed. RESULTS: Maternal characteristics including lower educational attainment, higher prepregnancy body mass index, gestational diabetes, lower vitamin D, and an unhealthy diet were associated with elevated levels of prenatal CRP and IL-8. Higher third trimester CRP and an increase in CRP from first to third trimester were associated with an increased odds of preterm birth when compared to lower levels of CRP (adjusted odds ratio [aOR] = 1.49, 95% confidence interval: 1.02, 2.23, p = 0.04) or a decrease in CRP over pregnancy (aOR = 3.06, 95% CI = 1.31,7.55, p = 0.01), after adjusting for potential confounders. These associations were strengthened when comparing only patients with spontaneous preterm birth (n = 22) to those with term births. CONCLUSION: Higher levels of the proinflammatory markers CRP and IL-8 are associated with indicators of poor maternal health and preterm birth. Prenatal CRP levels may reflect maternal prenatal health status and serve as a predictor of preterm birth, especially among those with spontaneous preterm birth. KEY POINTS: · Elevated prenatal CRP is associated with poor maternal health.. · High prenatal CRP may predict premature birth, especially spontaneous premature birth phenotypes.. · Vitamin D insufficiency may be a modifiable risk factor for prenatal inflammation..

The Association of Prenatal C-Reactive Protein Levels With Childhood Asthma and Atopy.

BACKGROUND: The pathogenesis of childhood asthma is complex, and determinants of risk may begin in utero. OBJECTIVE: To describe the association of systemic prenatal inflammation, measured by plasma C-reactive protein (CRP), with childhood asthma, eczema, and allergic rhinitis. METHODS: A total of 522 maternal-offspring pairs from the Vitamin D Antenatal Asthma Reduction Trial were included. Prenatal plasma CRP level was measured between 10 and 18 weeks of gestation and between 32 and 38 weeks of gestation. Offspring asthma, eczema, and allergic rhinitis were assessed quarterly between birth and age 6 years. We performed mediation analyses of prenatal CRP on the association between several maternal characteristics and offspring asthma. RESULTS: Elevated early and late prenatal CRP and an increase in CRP from early to late pregnancy were associated with asthma by age 6 years (early: adjusted odds ratio [aOR], 1.76, 95% CI, 1.12-2.82, P = .02; late: aOR, 2.45, 95% CI, 1.47-4.18, P < .001; CRP increase: aOR, 2.06, 95% CI, 1.26-3.39, P < .004). Prenatal CRP and childhood asthma associations were strengthened among offspring with atopic asthma (early: aOR, 3.78, 95% CI, 1.49-10.64, P = .008; late: aOR, 4.84, 95% CI, 1.68-15.50, P = .005; CRP increase: aOR, 3.01, 95% CI, 1.06-9.16, P = .04). Early and late prenatal CRP mediated 96% and 86% of the association between maternal prepregnancy body mass index and offspring asthma, respectively. CONCLUSIONS: Higher prenatal CRP and an increase in CRP from early to late pregnancy are associated with childhood asthma. Systemic inflammation during pregnancy associated with modifiable maternal characteristics may be an important determinant of childhood asthma risk.

Ambulatory Virtual Care During a Pandemic: Patient Safety Considerations.

BACKGROUND: The COVID-19 pandemic prompted sudden and fundamental changes in health care, including a rapid rise in the utilization of telehealth services in the ambulatory setting. With the unprecedented and significant decline in traditional office-based visits and procedures, novel patient safety risks and challenges emerged. METHODS: The ambulatory practices at our quaternary care, academic medical center experienced a 200-fold increase in virtual visit volume between February and April 2020. We convened a multidisciplinary working group dedicated to evaluating quality and safety when providing virtual visits during a pandemic. Our primary outcome was patient experience with virtual care delivery, which was assessed by leveraging patient complaint data and patient satisfaction survey data. RESULTS: For our main focus of patient experience and satisfaction, survey data were analyzed from the approximately 76,616 virtual visit encounters that occurred between March 1, 2020, and April 21, 2020. During this period, 5 patient complaints were filed to the Patient Advocacy Department. Overall, patient satisfaction with telehealth remained stable and high at >93% from February to May 2020. As we assessed these data each month, our working group developed risk mitigation strategies in response to the novel challenges presented by the use of telemedicine due to the COVID-19 pandemic while working to maintain patient satisfaction with care. We identified quality and safety issues around patient factors including optimal triage of patients and use of technology. We also evaluated accessibility to virtual platforms and logistics such as coordination of care for diagnostic testing. Finally, a guidance document was created and communicated to our diverse ambulatory practices to support clinicians. CONCLUSIONS: Ambulatory virtual care delivery requires a dynamic, flexible model of care through continuous rapid-cycle process improvement to mitigate patient safety risks during a pandemic, incorporating both provider and patient perspectives.

The Association of Prenatal Vitamin D Sufficiency With Aeroallergen Sensitization and Allergic Rhinitis in Early Childhood.

BACKGROUND: The role of prenatal vitamin D sufficiency and supplementation in the development of childhood aeroallergen sensitization and allergic rhinitis remains uncertain. OBJECTIVE: To describe the association of prenatal vitamin D sufficiency with childhood allergic outcomes in participants of the Vitamin D Antenatal Asthma Reduction Trial, a randomized controlled trial of prenatal vitamin D supplementation. METHODS: We included 414 mother-offspring pairs with offspring aeroallergen sensitization data available at age 6 years in this analysis. We examined the association between prenatal vitamin D sufficiency status, based on vitamin D levels measured in the first and third trimesters, or vitamin D supplementation treatment assignment with the outcomes of aeroallergen sensitization, parent-reported clinical allergic rhinitis, parent-reported clinical allergic rhinitis with aeroallergen sensitization, food sensitization, any sensitization, eczema, and total IgE at ages 3 and 6 years. RESULTS: Compared with early and late insufficiency, early prenatal vitamin D insufficiency with late sufficiency was associated with reduced development of clinical allergic rhinitis with aeroallergen sensitization at 3 years (adjusted odds ratio [aOR] = 0.34; 95% confidence interval [CI], 0.13-0.82; P = .02) and 6 years (aOR = 0.54; 95% CI, 0.29-0.98; P = .05). At 6 years, clinical allergic rhinitis with sensitization was significantly decreased in offspring whose mothers received high-dose vitamin D (aOR = 0.54; 95% CI, 0.32-0.91; P = .02) compared with offspring whose mothers who received low-dose vitamin D. Associations of prenatal vitamin D with aeroallergen sensitization were strengthened among children who also developed asthma or who had a maternal history of atopy. CONCLUSIONS: Among mothers with first-trimester vitamin D insufficiency, we detected a protective effect of third-trimester prenatal vitamin D sufficiency on the development of clinical allergic rhinitis with aeroallergen sensitization at ages 3 and 6 years.

Simulated Umbilical Venous Catheter Placement Improves Resident Competence and Confidence.

Background Pediatric ACGME (Accreditation Council for Graduate Medical Education) requirements include demonstrated competence in umbilical line placement. Given a waning number of these procedures clinically available to residents, new methods of procedural teaching must be employed. We developed a simulation-based strategy, using adult-learning principles, to teach umbilical venous catheter (UVC) placement to pediatric residents. We also determined whether procedural teaching via simulation increased confidence and competence among pediatric residents in performing the procedure. Methods Out of 23 first-year pediatric residents, eight participated in the study. Participants completed a survey evaluating their self-perceived competence and confidence in umbilical line placement. Their simulated umbilical line placement was assessed using a standardized checklist. Residents were then trained on simulated line placement in small groups by neonatologists. Six months later, residents completed a post-training survey and were assessed while placing simulated lines. Statistical analysis was completed using a paired t-test for parametric data, Wilcoxon signed-rank sum test for non-parametric data, and McNemar's chi-squared test for categorical data. Spearman's correlation was used for ordinal variables and Pearson's correlation was used for continuous variables. Results Nine PGY-1 (post-graduate year-1) residents completed the pre-training survey and simulation, while eight residents completed the post-training survey and simulation. There was an increase in resident confidence in placing umbilical lines six months after completion of the training session (p = 0.015) even though there was no difference in the number of umbilical lines that residents had placed in the intervening time. The residents performed a greater number of steps correctly after the training compared to their performance before the training (p=0.001). There was a statistically significant positive correlation between resident confidence and the number of steps performed correctly (rs(14)= 0.649, p = 0.006). There was no correlation between confidence and the number of umbilical lines placed on live subjects. Conclusion A teaching strategy that allows pediatric residents to struggle to perform UVC placement in a simulated setting, before receiving expert instruction, is effective at increasing their confidence and competence, even in the absence of exposure to human subjects.

Mining multi-site clinical data to develop machine learning MRI biomarkers: application to neonatal hypoxic ischemic encephalopathy.

BACKGROUND: Secondary and retrospective use of hospital-hosted clinical data provides a time- and cost-efficient alternative to prospective clinical trials for biomarker development. This study aims to create a retrospective clinical dataset of Magnetic Resonance Images (MRI) and clinical records of neonatal hypoxic ischemic encephalopathy (HIE), from which clinically-relevant analytic algorithms can be developed for MRI-based HIE lesion detection and outcome prediction. METHODS: This retrospective study will use clinical registries and big data informatics tools to build a multi-site dataset that contains structural and diffusion MRI, clinical information including hospital course, short-term outcomes (during infancy), and long-term outcomes (~ 2 years of age) for at least 300 patients from multiple hospitals. DISCUSSION: Within machine learning frameworks, we will test whether the quantified deviation from our recently-developed normative brain atlases can detect abnormal regions and predict outcomes for individual patients as accurately as, or even more accurately, than human experts. Trial Registration Not applicable. This study protocol mines existing clinical data thus does not meet the ICMJE definition of a clinical trial that requires registration.

Cannabis-related emergencies in children and teens.

PURPOSE OF REVIEW: To examine the spectrum of emergency department presentations associated with cannabis use or misuse that are currently seen in the pediatric population. RECENT FINDINGS: There is a growing concern that pediatric emergency department visits related to cannabis are on the rise, especially given rapidly changing legislation on cannabis and its broad availability in certain areas. These concerns are substantiated in the current literature, as the evidence mounts for an array of emergency department presentations of intentional or accidental cannabis use. The range of presentations documented in the recent literature spans gastrointestinal, psychiatric and cardiorespiratory effects, in addition to traumatic injuries and accidental ingestions by younger children. Complications of chronic cannabis use, such as 'cannabis hyperemesis syndrome', depression, psychosis or cognitive impairment, are now recognized outcomes and even more are likely to emerge. SUMMARY: An array of cannabis-related symptoms is possible from acute use or exposure. Common presentations include acute intoxication, hyperemesis, depression and acute physical injuries from impaired psychomotor function. Uncommon presentations include cardiorespiratory effects, and a range of symptoms in young children that include hyperkinesis and coma. Clinical vigilance is needed to suspect and clinically diagnose cannabis exposure in the emergency department.

Analysis of Oral Food Challenge Outcomes in IgE-Mediated Food Allergies to Almond in a Large Cohort.

BACKGROUND: Although almond specific IgE-mediated food allergies have traditionally been equated with other tree nut allergies, outcomes of oral food challenges to almond and the utility of clinical testing to predict IgE-mediated almond hypersensitivity are not well known. OBJECTIVE: To describe almond oral challenge outcomes and assess the predictive value of clinical testing. METHODS: A total of 603 almond challenges performed for 590 patients, aged 1 to 66 years, were analyzed from Massachusetts General Hospital allergy practices. Reactions were graded using the Niggemann and Beyer allergic reaction grading system and the Sampson 2006 National Institute of Allergy and Infectious Diseases anaphylaxis definition. RESULTS: Almond challenges included 545 passes (92%), 15 (3%) indeterminates, and 30 (5%) failures, in contrast with 31% challenge failures for other foods. Most reactions were mild; 21 (4%) had grade 2/3 allergic symptoms, and 3 (0.5%) had anaphylaxis. Median almond specific IgE level was 0.89 kU/L (range, <0.35 to >100 kU/L), median skin prick test wheal diameter was 4.0 mm (range, 0-28 mm), and 475 subjects (81%) were sensitized to almond. Failure was associated with higher almond specific IgE level (P < .001), larger almond skin prick test wheal diameter (P = .001), higher peanut IgE level (P = .003), and a history of almond reaction (P < .029). Almond specific IgE level, almond skin prick test wheal diameter, and age at challenge combined demonstrated good predictive value for grade 2/3 allergic reactions by receiver-operating characteristic analysis (area under the curve, 0.83). CONCLUSIONS: The proportion of failed almond challenges (5%) was low in contrast with other allergens, suggesting that some almond challenges may be safely conducted with higher patient-to-staff ratios or potentially introduced at home. Although reactions are usually uncommon and mild, anaphylaxis is possible with high almond sensitization.

Rifaximin suppresses background intestinal 18F-FDG uptake on PET/CT scans.

BACKGROUND: Identification of cancer or inflammatory bowel disease in the intestinal tract by PET/computed tomography (CT) imaging can be hampered by physiological uptake of F-fluorodeoxyglucose (F-FDG) in the normal colon. Previous work has localized this F-FDG uptake to the intestinal lumen, predominantly occupied by bacteria. We sought to determine whether pretreatment with an antibiotic could reduce F-FDG uptake in the healthy colon. PATIENTS AND METHODS: Thirty patients undergoing restaging PET/CT for nongastrointestinal lymphoma were randomly selected to receive rifaximin 550 mg twice daily for 2 days before their scan (post-rifaximin). Their PET/CT images were compared with those from their prior study (pre-rifaximin). Cecal maximum standard uptake value (SUVmax) and overall colonic F-FDG uptake were compared between scans. All PET/CT images were blindly scored by a radiologist. The same comparison of sequential scans was also undertaken in 30 patients who did not receive antibiotics. RESULTS: Thirty post-rifaximin scans were compared with 30 pre-rifaximin scans in the same patients. SUVmax in the cecum was significantly lower in the patient's post-rifaximin scans than in their pre-rifaximin scans (P=0.002). The percentage of scans with greater than grade 1 colonic F-FDG uptake was significantly lower in the post-rifaximin scans than in the pre-rifaximin scans (P<0.05). In contrast, there was no significant difference in the paired sequential scans from control patients, nor a reduction in the percentage of scans with greater than grade 1 colonic F-FDG uptake. CONCLUSION: This pilot study shows that treatment with rifaximin for 2 days before PET/CT scanning can significantly reduce physiological F-FDG uptake in the normal colonic lumen.

Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging.

UNLABELLED: The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging. METHODS: BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge. RESULTS: Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% ± 1.8% (P < 0.01). CONCLUSION: We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects.

Cold but not sympathomimetics activates human brown adipose tissue in vivo.

As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.

Focal physiologic fluorodeoxyglucose activity in the gastrointestinal tract is located within the colonic lumen.

AIM: Physiologic activity of 18F-fluorodeoxyglucose (FDG) in the intestinal tract occurs frequently in patients undergoing PET/computed tomography (CT) imaging, appearing most often in the colon. The purpose of this study is to determine the localization of the FDG within the colon. We hypothesize that intestinal FDG activity is intraluminal. METHODS: In a prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, patients with physiologic colonic FDG activity on PET/CT scans were enrolled to undergo repeat imaging 2 h after stimulation of colonic motility with a high-fat meal. RESULTS: We identified 13 patients who had focal FDG activity in their colon during a routine clinical PET/CT scan. After administration of a high-fat meal, 10 patients (77%) demonstrated antegrade movement of FDG along the colon, consistent with luminal clearance. CONCLUSION: Our results suggest that normal physiologic FDG activity within the large intestine, seen on PET/CT scans, is intraluminal.