A 3D-printed anatomical pancreas and kidney phantom for optimizing SPECT/CT reconstruction settings in beta cell imaging using 111In-exendin

Contains fulltext : 165641.pdf (publisher's version ) (Open Access)BACKGROUND: Quantitative single photon emission computed tomography (SPECT) is challenging, especially for pancreatic beta cell imaging with 111In-exendin due to high uptake in the kidneys versus much lower uptake in the nearby pancreas. Therefore, we designed a three-dimensionally (3D) printed phantom representing the pancreas and kidneys to mimic the human situation in beta cell imaging. The phantom was used to assess the effect of different reconstruction settings on the quantification of the pancreas uptake for two different, commercially available software packages. METHODS: 3D-printed, hollow pancreas and kidney compartments were inserted into the National Electrical Manufacturers Association (NEMA) NU2 image quality phantom casing. These organs and the background compartment were filled with activities simulating relatively high and low pancreatic 111In-exendin uptake for, respectively, healthy humans and type 1 diabetes patients. Images were reconstructed using Siemens Flash 3D and Hermes Hybrid Recon, with varying numbers of iterations and subsets and corrections. Images were visually assessed on homogeneity and artefacts, and quantitatively by the pancreas-to-kidney activity concentration ratio. RESULTS: Phantom images were similar to clinical images and showed comparable artefacts. All corrections were required to clearly visualize the pancreas. Increased numbers of subsets and iterations improved the quantitative performance but decreased homogeneity both in the pancreas and the background. Based on the phantom analyses, the Hybrid Recon reconstruction with 6 iterations and 16 subsets was found to be most suitable for clinical use. CONCLUSIONS: This work strongly contributed to quantification of pancreatic 111In-exendin uptake. It showed how clinical images of 111In-exendin can be interpreted and enabled selection of the most appropriate protocol for clinical use

Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature

Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD.'' All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations

Optimizing Multivitamin Supplementation for Sleeve Gastrectomy Patients

Purpose: Micronutrient deficiencies are frequently reported after sleeve gastrectomy (SG), and therefore lifelong daily multivitamin supplementation is highly recommended. Based on literature and the results of a previous randomized controlled trial, a specialized multivitamin supplement for SG patients was further optimized (WLS Optimum 2.0, FitForMe). The present study reports on its short-term effectiveness. Materials and Methods: An open-label study was performed in which 76 patients were included to receive WLS Optimum 2.0 for 12 months (Opt 2.0 group). This group was compared with a group of 75 patients that had received WLS Optimum 1.0 for 12 months during a previous study (Opt 1.0 group). Results: Intention-to-treat analysis (Opt 1.0, n = 69; Opt 2.0, n = 75) showed higher serum levels of vitamin B12, vitamin B6, and zinc, and a lower prevalence of deficiencies for vitamin B12 and phosphate in the Opt 2.0 group. MCV and serum folic acid levels were higher in the Opt 1.0 group. Over the 12-month study period, mean increase in serum levels of phosphate, vitamin B6, and zinc was higher in the Opt 2.0 group, and MCV and serum vitamin D levels increased more in the Opt 1.0 group. Conclusion: The present study showed that the use of a specialized multivitamin supplement for SG patients is effective at preventing deficiencies for most vitamins and minerals, specifically in compliant patients. However, a strict follow-up regime remains necessary to monitor nutritional status and to improve patient compliance

Relative validity of a short screener to assess diet quality in patients with morbid obesity before and after bariatric surgery

Objective: To determine the relative validity and reproducibility of the Eetscore FFQ, a short screener for assessing diet quality, in patients with (morbid) obesity before and after bariatric surgery (BS). Design: The Eetscore FFQ was evaluated against 3-day food records before (T0) and 6 months after BS (T6) by comparing index scores of the Dutch Healthy Diet index 2015 (DHD2015-index). Relative validity was assessed using paired t-tests, Kendall's tau-b correlation coefficients (τb), cross-classification by tertiles, weighted kappa values (k w) and Bland-Altman plots. Reproducibility of the Eetscore FFQ was assessed using intraclass correlation coefficients (ICC). Setting: Regional hospital, the Netherlands. Participants: 140 participants with obesity who were scheduled for BS. Results: At T0, mean total DHD2015-index score derived from the Eetscore FFQ was 10.2 points higher than the food record-derived score (P<0.001) and showed an acceptable correlation (τb=0.42, 95% CI: 0.27-0.55). There was a fair agreement with a correct classification of 50% (k w=0.37, 95% CI: 0.25-0.49). Correlation coefficients of the individual DHD components varied from 0.01-0.54. Similar results were observed at T6 (τb=0.31, 95% CI: 0.12-0.48, correct classification of 43.7%; k w=0.25, 95% CI: 0.11-0.40). Reproducibility of the Eetscore FFQ was good (ICC=0.78, 95% CI: 0.69-0.84). Conclusion: The Eetscore FFQ showed to be acceptably correlated with the DHD2015-index derived from 3-day food records but absolute agreement was poor. Considering the need for dietary assessment methods that reduce the burden for patients, practitioners and researchers, the Eetscore FFQ can be used for ranking according to diet quality and for monitoring changes over time

The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT

Background: Since a few years, the laparoscopic sleeve gastrectomy (SG) has become the most performed bariatric operation worldwide. However, as with all bariatric procedures, SG also leads to vitamin and mineral deficiencies post-operatively and standard multivitamin supplements are probably not sufficient. Objective: The present study evaluates the effectiveness of a specialized multivitamin supplement for SG patients (WLS Optimum 1.0, FitForMe, Rotterdam, the Netherlands), compared to a standard multivitamin supplement (sMVS). Design: A double-blind randomized controlled trial was performed. For 12 months, patients in the intervention group received WLS Optimum, containing elevated doses of multiple vitamins and minerals. Patients in the control group were provided with sMVS, containing 100% of the recommended dietary allowance. Results: In total, 139 patients were available for analysis (WLS Optimum, n = 69; sMVS, n = 70). Intention-to-treat analyses revealed more folic acid deficiencies and higher serum vitamin B1 levels in the WLS Optimum group. Per protocol analyses showed that in patients using WLS Optimum, serum folic acid and vitamin B1 levels were higher, serum PTH levels were lower, and only one patient (2.6%) was anemic compared to 11 patients (17.5%) using a sMVS (p < 0.05 for all). No differences were found in prevalence of deficiencies for iron, vitamin B12, vitamin D, and other vitamins and minerals. Conclusions: This optimized multivitamin supplement only affected serum levels of folic acid, PTH and vitamin B1, and anemia rates compared to a sMVS. There is a clear need to further optimize multivitamin supplementation for SG patients. Besides, non-compliance with multivitamin supplements remains an important issue that should be dealt with. Clinical Trial Registry: The study protocol was registered at the clinical trials registry of the National Institutes of Health (ClinicalTrials.gov; identifier NCT01609387).</p

Gastric pouch emptying of solid food in patients with successful and unsuccessful weight loss after Roux-en-Y gastric bypass surgery

Contains fulltext : 181531.pdf (publisher's version ) (Closed access

Treatment of Severe Protein Malnutrition After Bariatric Surgery

Background: Severe protein malnutrition, with a serum albumin 35 g/L after a median period of 58 days (range 44–171 days). Conclusion: In this case series, a continuous 24-h nasal-jejunal MCT tube feed combined with frequent pancreatic enzyme supplementation was effective in all patients presenting with severe post-bariatric hypoalbuminemia and was not associated with adverse effects.</p

Brain imaging of the GLP-1 receptor in obesity using68Ga-NODAGA-exendin-4 PET

Stimulation of glucagon-like peptide-1 (GLP-1) receptors increases the insulin release in the pancreas during high glucose levels, and also stimulates a feeling of satiety. Likewise, synthetic GLP-1 receptor agonists derived from exendin are used successfully in the treatment of type-2 diabetes mellitus and obesity. Interestingly, preclinical and clinical studies further suggest that GLP-1 receptor agonists may decrease motor, behavioral, and cognitive symptoms in (animal models) Parkinson’s disease and Alzheimer’s disease and may slow down neurodegeneration. These observations suggest stimulation of GLP-1 receptors in the brain. The GLP-1 positron emission tomography (PET) tracer68Ga-NODAGA-exendin-4 has been developed and successfully used for imaging in humans. In an ongoing study on the effects of bariatric surgery on GLP-1 receptor expression, we performed68Ga-NODAGA-exendin-4 PET in obese subjects. Here we evaluated whether GLP-1 receptor binding could be visualized in the central nervous system in 10 obese subjects (seven woman; body mass index: mean ± SD: 39 ± 4.4 kg/m2) before bariatric surgery. Although we observed clear uptake in the pituitary area (mean SUVmax 4.3 ± 2.3), we found no significant uptake in other parts of the brain. We conclude that68Ga-NODAGA-exendin-4 PET cannot be used to analyze GLP-1 receptors in the brain of obese subjects

Brain imaging of the GLP-1 receptor in obesity using68Ga-NODAGA-exendin-4 PET

Stimulation of glucagon-like peptide-1 (GLP-1) receptors increases the insulin release in the pancreas during high glucose levels, and also stimulates a feeling of satiety. Likewise, synthetic GLP-1 receptor agonists derived from exendin are used successfully in the treatment of type-2 diabetes mellitus and obesity. Interestingly, preclinical and clinical studies further suggest that GLP-1 receptor agonists may decrease motor, behavioral, and cognitive symptoms in (animal models) Parkinson’s disease and Alzheimer’s disease and may slow down neurodegeneration. These observations suggest stimulation of GLP-1 receptors in the brain. The GLP-1 positron emission tomography (PET) tracer68Ga-NODAGA-exendin-4 has been developed and successfully used for imaging in humans. In an ongoing study on the effects of bariatric surgery on GLP-1 receptor expression, we performed68Ga-NODAGA-exendin-4 PET in obese subjects. Here we evaluated whether GLP-1 receptor binding could be visualized in the central nervous system in 10 obese subjects (seven woman; body mass index: mean ± SD: 39 ± 4.4 kg/m2) before bariatric surgery. Although we observed clear uptake in the pituitary area (mean SUVmax 4.3 ± 2.3), we found no significant uptake in other parts of the brain. We conclude that68Ga-NODAGA-exendin-4 PET cannot be used to analyze GLP-1 receptors in the brain of obese subjects