Performance of pan-enteroscopy in children with intestinal failure due to short bowel syndrome: A single-center retrospective study.

OBJECTIVES: In pediatric patients with intestinal failure (IF) due to short bowel syndrome, we hypothesized that young children, those with shorter residual small bowel and those with congenital malrotation of the bowel would be more likely to undergo pan-enteroscopy. We aimed to determine the feasibility and diagnostic yield of pan-enteroscopy in this cohort. METHODS: We performed a single-center, retrospective study of pediatric patients with IF due to short bowel syndrome (SBS) who had undergone at least one GI endoscopic evaluation between January 1, 2018 and January 1, 2023. RESULTS: A pan-enteroscopy might have been possible in 381 of the 431 procedures (206 patients) reviewed. 44 (21%) patients underwent 54 pan-enteroscopies. Children with a residual bowel length <35 cm had higher odds of undergoing pan-enteroscopy (odds ratio [OR] 3.72, 95% confidence interval [CI] [1.32, 10.48], p = 0.01), as did patients with periprocedural glucagon-like peptide 2 (GLP-2) analog use (OR 4.30, 95% CI [1.24, 14.95], p = 0.02). Patients with diagnoses other than necrotizing enterocolitis (NEC) tended to be more likely to achieve a pan-enteroscopy (OR 2.73, 95% CI [0.95,7.88], p = 0.06). Evidence of gross and histopathologic abnormalities were found in 77.8% and 78% of the procedures, respectively. No complications were identified. CONCLUSION: In a large cohort of children with SBS, pan-enteroscopy was successfully performed in 14.2% of the procedures and microscopic abnormalities were common. Shorter residual bowel length, underlying diagnoses of non-NEC, and GLP-2 analog use were generally associated with successful pan-enteroscopy, independent of age and several other factors. These data suggest that pan-enteroscopy is feasible and of high-yield in a subset of patients with SBS.

Administration of 4% tetrasodium EDTA lock solution and central venous catheter complications in high-risk pediatric patients with intestinal failure: A retrospective cohort study.

BACKGROUND: Selection of central venous catheter (CVC) lock solution impacts catheter mechanical complications and central line-associated bloodstream infections (CLABSIs) in pediatric patients with intestinal failure. Disadvantages of the current clinical standards, heparin and ethanol lock therapy (ELT), led to the discovery of new lock solutions. High-risk pediatric patients with intestinal failure who lost access to ELT during a recent shortage were offered enrollment in a compassionate use trial with 4% tetrasodium EDTA (T-EDTA), a lock solution with antimicrobial, antibiofilm, and antithrombotic properties. METHODS: We performed a descriptive cohort study including 14 high-risk pediatric patients with intestinal failure receiving 4% T-EDTA as a daily catheter lock solution. CVC complications were documented (repairs, occlusions, replacements, and CLABSIs). Complication rates on 4% T-EDTA were compared with baseline rates, during which patients were receiving either heparin or ELT (designated as heparin/ELT). RESULTS: Patients initiated 4% T-EDTA at the time they were enrolled in the compassionate use protocol. Use of 4% T-EDTA resulted in a 50% reduction in CVC complications, compared with baseline rates on heparin/ELT (incidence rate ratio: 0.50; 95% CI, 0.25-1.004; P = 0.051). CONCLUSION: In a compassionate use protocol for high-risk pediatric patients with intestinal failure, the use of 4% T-EDTA reduced composite catheter complications, including those leading to emergency department visits, hospital admissions, additional procedures, and mortality. This outcome suggests 4% T-EDTA has benefits over currently available lock solutions.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). CONCLUSION: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

Implementation and participation of an online nutrition curriculum for pediatric gastroenterology fellows.

Our team of nutrition experts developed an online nutrition curriculum consisting of 21 modules to serve as a resource for a stand-alone nutrition curriculum or as a supplement to existing nutrition electives during the Pediatric Gastroenterology fellowship. From April 2020 through January 2023, 2090 modules were completed by 436 fellows from 75 different programs across North America. The program was accessed most during tight restrictions on in-person learning during the COVID-19 pandemic. Overall, participants posttest scores improved from baseline pretest scores indicating retention of information from the modules. The overall success of this program suggests that there should be continued efforts to develop and offer online learning opportunities in clinical nutrition. There is an opportunity to expand the audience for the curriculum to include pediatric gastroenterologists from across the globe.

Glycemic and sleep effects of daytime compared with those of overnight infusions of home parenteral nutrition in adults with short bowel syndrome: A quasi-experimental pilot trial.

BACKGROUND: Patients with short bowel syndrome (SBS) dependent on home parenteral nutrition (HPN) commonly cycle infusions overnight, likely contributing to circadian misalignment and sleep disruption. METHODS: The objective of this quasi-experimental, single-arm, controlled, pilot trial was to examine the feasibility, safety, and efficacy of daytime infusions of HPN in adults with SBS without diabetes. Enrolled patients were fitted with a continuous glucose monitor and wrist actigraph and were instructed to cycle their infusions overnight for 1 wk, followed by daytime for another week. The 24-h average blood glucose, the time spent >140 mg/dL or <70 mg/dL, and sleep fragmentation were derived for each week and compared using Wilcoxon signed-rank test. Patient-reported quality-of-life outcomes were also compared between the weeks. RESULTS: Twenty patients (mean age, 51.7 y; 75% female; mean body mass index, 21.5 kg/m2) completed the trial. Overnight infusions started at 21:00 and daytime infusions at 09:00. No serious adverse events were noted. There were no differences in 24-h glycemia (daytime-median: 93.00 mg/dL; 95% CI: 87.7-99.9 mg/dL, compared with overnight-median: 91.1 mg/dL; 95% CI: 89.6-99.0 mg/dL; P = 0.922). During the day hours (09:00-21:00), the mean glucose concentrations were 13.5 (5.7-22.0) mg/dL higher, and the time spent <70 mg/dL was 15.0 (-170.0, 22.5) min lower with daytime than with overnight HPN. Conversely, during the night hours (21:00-09:00), the glucose concentrations were 16.6 (-23.1, -2.2) mg/dL lower with daytime than with overnight HPN. There were no differences in actigraphy-derived measures of sleep and activity rhythms; however, sleep timing was later, and light at night exposure was lower with daytime than with overnight HPN. Patients reported less sleep disruptions due to urination and fewer episodes of uncontrollable diarrhea or ostomy output with daytime HPN. CONCLUSIONS: Daytime HPN was feasible and safe in adults with SBS and, compared with overnight HPN, improved subjective sleep without increasing 24-h glucose concentrations. This trial was registered at clinicaltrials.gov as NCT04743960 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04743960).

Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide.

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration. Pediatric-specific postmarketing studies evaluating long-term safety and efficacy are underway. Formation of colorectal polyps has been repeatedly observed in studies of adult patients on long-term teduglutide, including in individuals without endoscopic evidence of polyps before treatment initiation. Recent studies, however, suggest increased risk of small bowel hyperplastic and dysplastic polyp formation with long-term glucagon-like peptide 2 analog use. We report 2 cases of small bowel foveolar hyperplastic polyps found during surveillance endoscopies after 1 year of treatment with teduglutide.

Air Displacement Plethysmography is an Accurate and Feasible Noninvasive Measure of Fat-Free Mass in Children With Intestinal Failure.

BACKGROUND: The nutritional status of children with intestinal failure (IF) can be difficult to determine using body weight and currently available anthropometric techniques. Air displacement plethysmography (ADP) is a noninvasive measure of whole-body composition that measures body mass and volume, with a calculation of percent body fat (%BF) and fat-free mass (FFM) that may be useful during the provision of specialized nutrition. OBJECTIVES: To evaluate the validity and feasibility of measuring body composition in children with IF using ADP compared with deuterium dilution (DD), as well as secondarily with other measures of body composition, namely bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and four-site skinfold anthropometry. METHODS: We conducted a prospective cohort study of 18 children recruited through the Center for Advanced Intestinal Rehabilitation at Boston Children's Hospital. Patients 2-17 years of age with IF dependent on parenteral nutrition (PN) for more than 90 days were included. Spearman rank correlation and Bland-Altman limits of agreement (LOA) analysis were used to compare ADP to 4 alternative measures of body composition. RESULTS: Eighteen children with IF, median age 7.1 [interquartile range (IQR) 5.4-9.3] years, 9 female (50%), and median residual bowel length 31 (IQR 22-85) cm were enrolled. Median PN energy intake was 46 (IQR 39-49) kcal/kg/day. Incomplete bladder emptying lead to invalid measures of DD in 4 subjects. Spearman correlation coefficients for %BF were low to moderate between ADP and DD ( r = 0.29), DXA ( r = 0.62), BIA ( r = 0.50), and skinfold ( r = 0.40). Correlations for FFM were high between ADP and these other measures (range 0.95-0.98). Comparing ADP with DD and skinfold measures, Bland-Altman analysis showed small mean bias (-1.9 and +1.5 kg) and acceptable 95% LOA ranges (10.7 and 22.9 kg), respectively, with larger bias (-10.7 and -7.7 kg) and LOA ranges (38.7 and 45.2 kg) compared to DXA and BIA. %BF by ADP and skinfold thickness were moderately correlated ( r = 0.43) with low bias (-0.2%) but very wide LOA (25.7%). CONCLUSIONS: Body composition via ADP is feasible and valid in children with IF as a measure of FFM but appears less suitable for the measurement of %BF. The technique holds promise as a noninvasive measure of body composition to assess the efficacy of nutritional, medical, and surgical interventions.

Nutritional and medical approaches to intestinal failure.

PURPOSE OF REVIEW: Advances in the field of intestinal failure continue to reduce mortality rates of this complex syndrome. Over the last 20 months (January 2021- October 2022), several important papers were published that relate to the nutritional and medical management of intestinal failure and rehabilitation. RECENT FINDINGS: New reports on the epidemiology of intestinal failure have shown that short bowel syndrome (SBS) remains the most common cause of intestinal failure worldwide in both adults and children. Advances in the provision of parenteral nutrition (PN), the advent of Glucagon-like peptide-2 (GLP-2) analogs, and the development of interdisciplinary centers have allowed for safer and longer courses of parenteral support. Unfortunately, rates of enteral anatomy continue to lag behind these advancements, requiring greater focus on quality of life, neurodevelopmental outcomes, and management of sequalae of long-term PN such as Intestinal Failure Associated Liver Disease (IFALD), small bowel bacterial overgrowth (SBBO), and Metabolic Bone Disease (MBD). SUMMARY: There have been significant advances in the nutritional and medical approaches in intestinal failure, including advances in PN, use of GLP-2 analogs, and key developments in the medical management of this condition. As children with intestinal failure increasingly survive to adulthood, new challenges exist with respect to the management of a changing population of patients with SBS. Interdisciplinary centers remain standard of care for this complex patient population.

Ethanol lock therapy increases mechanical catheter complications in a pediatric intestinal failure population: A retrospective cohort study.

BACKGROUND: Ethanol lock therapy (ELT) decreases central line-associated bloodstream infections; however, the effect on mechanical catheter complications is unclear. In recent years, ELT has become unavailable for many patients, often resulting in high-risk patients switching back to heparin locks. We investigated the impact of ELT on mechanical catheter complications during this period. METHODS: We performed a retrospective cohort study of the Boston Children's Hospital intestinal rehabilitation program from January 1, 2018, to December 31, 2020. Pediatric patients with a central venous catheter requiring parenteral support for 3 months were included. The primary outcome was the composite rate of mechanical catheter complications (repairs and replacements). RESULTS: The pediatric intestinal failure cohort consisted of 122 patients. Forty-four percent received ELT for the entirety of the study period, 29% used only heparin locks, and 27% used ELT and heparin locks at different periods. During ELT use, there was 1.65 times the risk of mechanical catheter complications (composite outcome of repairs and replacements) compared with heparin locks (adjusted incidence rate ratio [aIRR] = 1.65, 95% CI = 1.18-2.31). Current ELT use was associated with 2.3 times the risk of catheter repairs (aIRR = 2.30, 95% CI = 1.36-3.89) but no significant increase in catheter replacement risk (aIRR = 1.41, 95% CI = 0.91-2.20). CONCLUSION: In the largest pediatric intestinal failure cohort evaluated to date, the use of ELT, compared with heparin locks, increased the risk of mechanical catheter complications. Mechanical complications carry morbidity requiring urgent clinic or emergency department visits and additional procedures. The investigation of alternative lock solutions is warranted.

Factors Associated With Chronic Intestinal Inflammation Resembling Inflammatory Bowel Disease in Pediatric Intestinal Failure: A Matched Case-Control Study.

BACKGROUND AND AIMS: There is a subset of intestinal failure patients with associated chronic intestinal inflammation resembling inflammatory bowel disease. This study aimed to evaluate factors associated with chronic intestinal inflammation in pediatric intestinal failure. METHODS: This was a single-center retrospective case-control study of children <18 years old with intestinal failure. Cases were defined by abnormal amounts of chronic intestinal inflammation on biopsies. Children with diversion colitis, eosinophilic colitis, or isolated anastomotic ulceration were excluded. Cases were matched 1:2 to intestinal failure controls based on sex, etiology of intestinal failure, and duration of intestinal failure. Multivariable conditional logistic regression was used to compare clinical factors between cases and controls, accounting for clustering within matched sets. A subgroup analysis was performed assessing factors associated with escalation of anti-inflammatory therapy. RESULTS: Thirty cases were identified and matched to 60 controls. On univariate analysis, longer parenteral nutrition (PN) duration (1677 vs 834 days, P = 0.03), current PN use (33.3% vs 20.0%, P = 0.037), and culture-proven bacterial overgrowth (53.3% vs 31.7%, P = 0.05) were associated with chronic intestinal inflammation. On multivariable analysis, no variable reached statistical significance. On subgroup analysis, duration of intestinal failure, location of inflammation, and worst degree of inflammation on histology were associated with escalation of therapy. CONCLUSIONS: PN dependence and intestinal dysbiosis are associated with chronic intestinal inflammation in children with intestinal failure. Severity of inflammation is associated with escalation of therapy. Further analysis is needed to assess these associations and the efficacy of treatments in this population.

High Rate of Venous Thromboembolism in Severe Pediatric Intestinal Failure.

OBJECTIVE: To quantify the rate of venous thromboembolism (VTE) in patients with pediatric intestinal failure and identify associated risk factors. STUDY DESIGN: We performed a retrospective cohort study in pediatric patients (<21 years old) with severe pediatric intestinal failure (≥90 consecutive days of parenteral nutrition) secondary to short bowel syndrome who were treated from 2014 to 2021 at an interdisciplinary intestinal rehabilitation program. The primary outcome was the incidence of VTE. Multivariable regression was performed to identify independent clinical predictors of VTE. RESULTS: A total of 263 patients (59.7% male) met the criteria for inclusion. The cumulative incidence of VTE was 28.1%, with a rate of 0.32 VTEs per 1000 catheter-days. On univariate analysis, the number of catheter days, number of catheters, and history of central line-associated blood stream infection were associated with VTE. On multivariable logistic regression, a higher number of catheters was an independent risk factor for VTE (aOR, 1.17; 95% CI, 1.06-1.29). Additionally, earlier gestational age was a risk factor for VTE such that every week decrease in gestational age conferred a 9% increased risk of VTE (aOR, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: In this retrospective study, 28.1% of patients with severe pediatric intestinal failure developed VTE; the number of catheters and early gestational age were noted to be independent risk factors for VTE. This high incidence of VTE highlights the need to investigate VTE in pediatric intestinal failure prospectively, including the potential benefit of prophylactic anticoagulation.

Antibiotic Therapy for Culture-Proven Bacterial Overgrowth in Children With Intestinal Failure Results in Improved Symptoms and Growth.

OBJECTIVES: To evaluate symptoms, enteral tolerance, growth, and antibiotic regimens in pediatric intestinal failure (IF) patients after treated with antibiotic therapy for small bowel bacterial overgrowth (SBBO). METHODS: Single-center retrospective review of children 0-18 years with IF with endoscopic cultures demonstrating >10 5 CFU/mL from 2010 to 2017. Symptoms, enteral tolerance, growth, and antibiotic regimens were evaluated at the time of endoscopy and 6 months later. RESULTS: Of 505 patients followed in our intestinal rehabilitation program, 104 underwent upper gastrointestinal endoscopy and 78 had positive duodenal cultures. Clinical data pre- and post-endoscopy were available for 56 patients. Compared to baseline, in the 6 months following targeted antibiotic treatment, children showed significant improvement in emesis or feeding intolerance (58.9% vs 23.2%, P < 0.001), abdominal pain (16.1% vs 7.1%, P = 0.02), high stool output (42.9% vs 19.6%, P = 0.002), and gross GI bleeding (19.6% vs 3.6%, P = 0.003). Mean BMI-for-age z scores increased significantly (-0.03 ± 0.94 vs 0.27 ± 0.82, P = 0.03); however, height-for-age z scores, weight-for-age z scores, and percent of calories from enteral intake were not significantly different after therapy. Antibiotic regimens remained highly variable. CONCLUSIONS: Children with IF and culture-positive SBBO showed significant improvement in symptoms and BMI-for-age z scores after duodenal culture with subsequent targeted antibiotic therapy. Longer follow-up may be needed to detect improvements in linear growth and percent of calories from enteral feeds. Antibiotic regimens remain highly variable. Long-term consequences of chronic antimicrobial therapy, including antimicrobial resistance, remain unknown. Prospective studies focused on standardizing duodenal sampling technique, correlating culture and pathology data, and evaluating antibiotic resistance patterns are needed.

Monash DaCRA fPET-fMRI: A dataset for comparison of radiotracer administration for high temporal resolution functional FDG-PET.

BACKGROUND: "Functional" [18F]-fluorodeoxyglucose positron emission tomography (FDG-fPET) is a new approach for measuring glucose uptake in the human brain. The goal of FDG-fPET is to maintain a constant plasma supply of radioactive FDG in order to track, with high temporal resolution, the dynamic uptake of glucose during neuronal activity that occurs in response to a task or at rest. FDG-fPET has most often been applied in simultaneous BOLD-fMRI/FDG-fPET (blood oxygenation level-dependent functional MRI fluorodeoxyglucose functional positron emission tomography) imaging. BOLD-fMRI/FDG-fPET provides the capability to image the 2 primary sources of energetic dynamics in the brain, the cerebrovascular haemodynamic response and cerebral glucose uptake. FINDINGS: In this Data Note, we describe an open access dataset, Monash DaCRA fPET-fMRI, which contrasts 3 radiotracer administration protocols for FDG-fPET: bolus, constant infusion, and hybrid bolus/infusion. Participants (n = 5 in each group) were randomly assigned to each radiotracer administration protocol and underwent simultaneous BOLD-fMRI/FDG-fPET scanning while viewing a flickering checkerboard. The bolus group received the full FDG dose in a standard bolus administration, the infusion group received the full FDG dose as a slow infusion over the duration of the scan, and the bolus-infusion group received 50% of the FDG dose as bolus and 50% as constant infusion. We validate the dataset by contrasting plasma radioactivity, grey matter mean uptake, and task-related activity in the visual cortex. CONCLUSIONS: The Monash DaCRA fPET-fMRI dataset provides significant reuse value for researchers interested in the comparison of signal dynamics in fPET, and its relationship with fMRI task-evoked activity.

Task-evoked simultaneous FDG-PET and fMRI data for measurement of neural metabolism in the human visual cortex.

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18-49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics.

A clinical trial of non-invasive imaging with an anti-HIV antibody labelled with copper-64 in people living with HIV and uninfected controls.

BACKGROUND: A research priority in finding a cure for HIV is to establish methods to accurately locate and quantify where and how HIV persists in people living with HIV (PLWH) receiving suppressive antiretroviral therapy (ART). Infusing copper-64 (64Cu) radiolabelled broadly neutralising antibodies targeting HIV envelope (Env) with CT scan and positron emission tomography (PET) identified HIV Env in tissues in SIV infected non-human primates . We aimed to determine if a similar approach was effective in people living with HIV (PLWH). METHODS: Unmodified 3BNC117 was compared with 3BNC117 bound to the chelator MeCOSar and 64Cu (64Cu-3BNC117) in vitro to assess binding and neutralization. In a clinical trial 64Cu-3BNC117 was infused into HIV uninfected (Group 1), HIV infected and viremic (viral load, VL >1000 c/mL; Group 2) and HIV infected aviremic (VL <20 c/mL; Group 3) participants using two dosing strategies: high protein (3mg/kg unlabeled 3BNC117 combined with <5mg 64Cu-3BNC117) and trace (<5mg 64Cu-3BNC117 only). All participants were screened for 3BNC117 sensitivity from virus obtained from viral outgrowth. Magnetic resonance imaging (MRI)/PET and pharmacokinetic assessments (ELISA for serum 3BNC117 concentrations and gamma counting for 64Cu) were performed 1, 24- and 48-hours post dosing. The trial (clincialtrials.gov NCT03063788) primary endpoint was comparison of PET standard uptake values (SUVs) in regions of interest (e.g lymph node groups and gastrointestinal tract). FINDINGS: Comparison of unmodified and modified 3BNC117 in vitro demonstrated no difference in HIV binding or neutralisation. 17 individuals were enrolled of which 12 were dosed including Group 1 (n=4, 2 high protein, 2 trace dose), Group 2 (n=6, 2 high protein, 4 trace) and Group 3 (n=2, trace only). HIV+ participants had a mean CD4 of 574 cells/microL and mean age 43 years. There were no drug related adverse effects and no differences in tissue uptake in regions of interest (e.g lymph node gut, pharynx) between the 3 groups. In the high protein dosing group, serum concentrations of 3BNC117 and gamma counts were highly correlated demonstrating that 64Cu-3BNC117 remained intact in vivo. INTERPRETATION: In PLWH on or off ART, the intervention of infusing 64Cu-3BNC117 and MRI/PET imaging over 48 hours, was unable to detect HIV-1 env expression in vivo. Future studies should investigate alternative radiolabels such as zirconium which have a longer half-life in vivo. FUNDING: Funded by the Alfred Foundation, The Australian Centre for HIV and Hepatitis Virology Research with additional support from the Division of AIDS, National Institute of Allergy and Infectious Disease, US National Institutes of Health (USAI126611). JHM and SRL are supported by the Australian National Health and Medical Research Council.

Augmented deep learning model for improved quantitative accuracy of MR-based PET attenuation correction in PSMA PET-MRI prostate imaging.

PURPOSE: Estimation of accurate attenuation maps for whole-body positron emission tomography (PET) imaging in simultaneous PET-MRI systems is a challenging problem as it affects the quantitative nature of the modality. In this study, we aimed to improve the accuracy of estimated attenuation maps from MRI Dixon contrast images by training an augmented generative adversarial network (GANs) in a supervised manner. We augmented the GANs by perturbing the non-linear deformation field during image registration between MRI and the ground truth CT images. METHODS: We acquired the CT and the corresponding PET-MR images for a cohort of 28 prostate cancer patients. Data from 18 patients (2160 slices and later augmented to 270,000 slices) was used for training the GANs and others for validation. We calculated the error in bone and soft tissue regions for the AC µ-maps and the reconstructed PET images. RESULTS: For quantitative analysis, we use the average relative absolute errors and validate the proposed technique on 10 patients. The DL-based MR methods generated the pseudo-CT AC µ-maps with an accuracy of 4.5% more than standard MR-based techniques. Particularly, the proposed method demonstrates improved accuracy in the pelvic regions without affecting the uptake values. The lowest error of the AC µ-map in the pelvic region was 1.9% for µ-mapGAN + aug compared with 6.4% for µ-mapdixon, 5.9% for µ-mapdixon + bone, 2.1% for µ-mapU-Net and 2.0% for µ-mapU-Net + aug. For the reconstructed PET images, the lowest error was 2.2% for PETGAN + aug compared with 10.3% for PETdixon, 8.7% for PETdixon + bone, 2.6% for PETU-Net and 2.4% for PETU-Net + aug.. CONCLUSION: The proposed technique to augment the training datasets for training of the GAN results in improved accuracy of the estimated µ-map and consequently the PET quantification compared to the state of the art.

One-year Experience With Composite Intravenous Lipid Emulsion in Children on Home Parenteral Nutrition.

BACKGROUND: Composite lipid emulsion (CLE) composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil is approved in the US for parenterally fed adults. For stable children discharged on home parenteral nutrition (HPN) without cholestasis (direct bilirubin > 2.0 mg/dL), CLE has theoretical benefits over soybean-based intravenous lipid emulsion due to reduced phytosterol exposure with higher calorie support to permit reduced glucose infusion rates (GIRs), omega-3 supplementation, and supplemental α-tocopherol. METHODS: In this prospective, single-center open-label research study, safety and efficacy outcomes were evaluated in patients on HPN younger than 18 years treated with CLE at 1 to 3 g ·â€Škg-1 ·â€Šday-1 over 12 months. The primary outcome was change in anthropometrics and GIRs compared with baseline. Secondary outcomes were changes in fatty acid profiles and liver function and enzyme tests compared with baseline. RESULTS: Fifty-seven subjects were treated with a median age of 7 years. The diagnosis was short bowel syndrome in 72%. Change in practice was associated with a decrease in mean GIRs from 17 to 14 mg ·â€Škg-1 ·â€Šh-1 at 4 to 6 months postbaseline and beyond with a coincidental decline in mean arachidonic acid and stable growth parameters. No significant adverse events were noted. CONCLUSIONS: CLE was safe and well-tolerated in stable children on HPN at 1 year, but further studies are needed in this population to appreciate long-term outcomes.

Radiotracer Administration for High Temporal Resolution Positron Emission Tomography of the Human Brain: Application to FDG-fPET.

Functional positron emission tomography (fPET) provides a method to track molecular targets in the human brain. With a radioactively-labelled glucose analogue, 18F-fluordeoxyglucose (FDG-fPET), it is now possible to measure the dynamics of glucose metabolism with temporal resolutions approaching those of functional magnetic resonance imaging (fMRI). This direct measure of glucose uptake has enormous potential for understanding normal and abnormal brain function and probing the effects of metabolic and neurodegenerative diseases. Further, new advances in hybrid MR-PET hardware make it possible to capture fluctuations in glucose and blood oxygenation simultaneously using fMRI and FDG-fPET. The temporal resolution and signal-to-noise of the FDG-fPET images is critically dependent upon the administration of the radiotracer. This work presents two alternative continuous infusion protocols and compares them to a traditional bolus approach. It presents a method for acquiring blood samples, time-locking PET, MRI, experimental stimulus, and administering the non-traditional tracer delivery. Using a visual stimulus, the protocol results show cortical maps of the glucose-response to external stimuli on an individual level with a temporal resolution of 16 s.

Caregiver Training for Pediatric Home Parenteral Nutrition: A 5-Session Discharge Curriculum.

To maximize safety and the patient experience, caregivers require intensive training to administer home parenteral nutrition (HPN) before initial hospital discharge. This article provides the rationale, best practices, and a template for caregiver predischarge HPN education provided by nurses. The standardized HPN discharge curriculum is outlined over 5 didactic and hands-on sessions.