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Transcatheter Bariatric Embolotherapy for Weight Reduction in Obesity.
Reddy, VY, Neužil, P, Musikantow, D, Sramkova, P, Rosen, R, Kipshidze, N, Kipshidze, N, Fried, M
Journal of the American College of Cardiology. 2020;(20):2305-2317
Abstract
BACKGROUND Obesity is well-appreciated to result in poor cardiovascular and metabolic outcomes. Dietary and medical weight loss strategies are frequently unsuccessful and unsustainable. Bariatric surgery is quite effective, but is reserved for the most obese patients because of the associated intraoperative/post-operative risks. In preclinical and early clinical case series, a novel therapy, transcatheter bariatric embolotherapy (TBE) of the left gastric artery, has been reported to promote weight loss by reducing ghrelin, an appetite-stimulating hormone secreted from the gastric fundus. OBJECTIVES The purpose of this study was to examine TBE in a single-blind, sham procedure randomized trial. METHODS Obese subjects (body mass index 35 to 55 kg/m2) were randomized 1:1 to either sham or TBE targeting the left gastric artery using an occlusion balloon microcatheter to administer 300- to 500-μm embolic beads. All patients entered a lifestyle counseling program. Patients and physicians performing follow-up were blind to the allocated therapy. Endoscopy was performed at baseline and 1-week post-procedure. The primary endpoint was 6-month total body weight loss (TBWL). RESULTS Eligible subjects (n = 44; age 45.5 ± 9.4 years; 8 men/36 women; body mass index 39.6 ± 3.8 kg/m2) were randomized to undergo the sham or TBE procedure with no device-related complications and 1 vascular complication. Patients reported mild nausea and vomiting, and endoscopy revealed only minor self-limiting ulcers in 5 patients. At 6 months, in both the intention-to-treat and per-protocol populations, the TBWL was greater with TBE (7.4 kg/6.4% and 9.4 kg/8.3% loss, respectively) than sham (3.0 kg/2.8% and 1.9 kg/1.8%, respectively; p = 0.034/0.052 and p = 0.0002/0.0011, respectively). The TBWL was maintained with TBE at 12 months (intention-to-treat 7.8 kg/6.5% loss, per-protocol 9.3 kg/9.3% loss; p = 0.0011/0.0008, p = 0.0005/0.0005, respectively). CONCLUSIONS In this randomized pilot trial, we have established the proof-of-principle that transcatheter bariatric embolotherapy of the left gastric artery is well-tolerated and promotes clinically significant weight loss over a sham procedure.(The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial [LOSEIT]; NCT03185949).
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Gastric and Postgastric Processing of 13C Markers Renders the 13C Breath Test an Inappropriate Measurement Method for the Gastric Emptying of Lipid Emulsions in Healthy Adults.
Parker, HL, Liu, D, Curcic, J, Ebert, MO, Schwizer, W, Fried, M, Steingoetter, A
The Journal of nutrition. 2017;(7):1258-1266
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Abstract
Background: Breath tests (BTs) present an alternative gastric-emptying (GE) measure. However, their efficacy in the measurement of the GE rate of lipid emulsions (LEs) is unknown.Objective: The objective of this work was to investigate the validity of 13C BTs as a measure of fat GE rate in LEs.Methods: The lipophilic 13C octanoate (OCC) BT marker was investigated for fat GE with the hydrophilic 13C sodium acetate (ACC) and the triglyceride 13C trioctanoin (TCC) markers as comparators. Data from 2 randomized studies were combined [50 healthy participants; 25 men, mean ± SD age: 23 ± 2.8 y; mean ± SD body mass index (in kg/m2): 22.4 ± 1.7]. Each participant was given either an acid-stable LE (LE1) or an acid-unstable LE (LE4) at each visit. Twenty-three participants underwent simultaneous MRI. The effect of LEs on 13CO2 excretion profiles was determined. The BT half-emptying times (BT T50) were validated with the MRI half-emptying time of the ingested fat volume (MRI T50).Results: The effect of LEs on 13CO2 excretion depended on the properties of the 13C marker. T50 for OCC was shorter by 98 min for LE1 than for LE4 (P < 0.001). Other markers showed either no LE dependency or a longer T50 for LE1 than for LE4. No difference in T50 between OCC and ACC was detected in LE1. In LE4, the T50 was longer by 154 min (P < 0.0001). There was some concordance between MRI T50 and OCC BT T50 for LE1 (rc = 0.7). No other marker showed any concordance with fat GE. 13C-Nuclear magnetic resonance in vitro findings were compatible with changes in the kinetics of phase transfer of OCC dependent on its protonation state.Conclusions: The structure of fat present in the stomach affects 13CO2 excretion. The chemical properties of the 13C marker and their gastric and postgastric interaction with fat renders 13CO2 excretion an inappropriate measure of LE emptying in healthy adults. This trial was registered at clinicaltrials.gov as NCT02226029 and NCT02602158.
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The visualisation and quantification of human gastrointestinal fat distribution with MRI: a randomised study in healthy subjects.
Liu, D, Parker, HL, Curcic, J, Schwizer, W, Fried, M, Kozerke, S, Steingoetter, A
The British journal of nutrition. 2016;(5):903-12
Abstract
We aimed to study the fate of fat during digestion. For this purpose, we validated and investigated the non-invasive quantification of gastric and duodenal fat emptying and emulsion processing (creaming and phase separation) using the MRI method iterative decomposition with echo asymmetry and least squares estimation (IDEAL). In total, twelve healthy subjects were studied on two separate visits in a single-blind, randomised, cross-over design study. IDEAL was utilised to repeatedly acquire quantitative fat fraction maps of the gastrointestinal tract after infusion of one of two fat emulsions: E1 (acid stable, droplet size 0·33 mm) and E4 (acid unstable, 0·38 mm). In vitro and in vivo validation was carried out using diluted emulsion and gastric content samples, respectively, and resulted in Lin's concordance correlation coefficients of 1·00 (95% CI 0·98, 1·00) and 0·91 (95% CI 0·87, 0·94), respectively. Fat fraction maps and intragastric emulsion profiles enabled the identification of features of intraluminal phase separation and creaming that were not visible in conventional MRI. Gastric fat emptying was faster for E4 compared with E1 with a difference of 2·5 (95% CI 1·9, 3·1) ml/h. Duodenal content volumes were larger for E1 than for E4 with a difference of 4·9 (95% CI 3·9, 8·5) ml. This study demonstrated that with IDEAL it was possible (1) to visualise the intragastric and duodenal fat distribution and (2) to quantify the differences in emptying, phase separation and creaming of an acid-stable and an acid-unstable emulsion. This method has potential to bridge the gap between current in vitro digestive models and in vivo behaviour and to be applied in the development of effective functional foods.
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Prevalence of Plasmodium falciparum anti-malarial resistance-associated polymorphisms in pfcrt, pfmdr1 and pfnhe1 in Muheza, Tanzania, prior to introduction of artemisinin combination therapy.
Gadalla, NB, Tavera, G, Mu, J, Kabyemela, ER, Fried, M, Duffy, PE, Sá, JM, Wellems, TE
Malaria journal. 2015;:129
Abstract
BACKGROUND A report of the chloroquine and amodiaquine resistance pfcrt-SVMNT haplotype in Tanzania raises concern about high-level resistance to the artesunate-amodiaquine combination treatment widely employed in Africa. Mutations in the pfmdr1 multi-drug resistance gene may also be associated with resistance, and a highly polymorphic microsatellite (ms-4760) of the pfnhe1 gene involved in quinine susceptibility has not been surveyed in Tanzania. METHODS A total of 234 samples collected between 2003 - 2006 from an observational birth cohort of young children in Muheza, Tanzania were analysed. In these children, 141 cases of P. falciparum infections were treated with AQ and 93 episodes were treated with QN. Haplotypes of pfcrt and pfmdr1 were determined by a Taqman assay, and ms-4760 repeats in pfnhe1 were assessed by nested PCR amplification and direct sequencing. Parasite population diversity was evaluated using microsatellite markers on five different chromosomes. RESULTS The pfcrt-CVIET haplotype was present alone in 93.6% (219/234) of the samples over the study period; the wild-type chloroquine- and amodiaquine-sensitive haplotype pfcrt-CVMNK was present in 4.3% (10/234) of the samples; and both haplotypes were present in 2.1% (5/234) of the samples. No significant change in wild-type pfcrt-CVMNK prevalence was evident over the 4-year period of the study. The pfcrt-SVMNT haplotype associated with high-level amodiaquine resistance was not detected in this study. The pfmdr1 locus was genotyped in 178 of these samples. The pfmdr1-YYNY haplotype predominated in 67.4% (120/178) of infections and was significantly associated with the pfcrt-CVIET haplotype. All samples carried the wild-type pfmdr1-N1042 codon. The ms-4760 repeat on pfnhe1 locus displayed 12 distinct haplotypes with ms-4760-1 predominating in the population. Analysis of these haplotypes showed no association of a particular haplotype with quinine treatment outcome. CONCLUSION The pfcrt-CVIET chloroquine resistance haplotype dominated in the collection of P. falciparum samples from Muheza. The pfcrt-SVMNT haplotype, which threatens the efficacy of amodiaquine and was reported in the same time period from Korogwe, Tanzania, 40 Km from Muheza, was not detected. Relative low prevalence of pfcrt-SVMNT in Africa may result from genetic or other factors rendering P. falciparum less supportive of this haplotype than in South America or other regions. TRIAL REGISTRATION Trial Protocol Number: 08-I-N064.
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Volume, distribution and acidity of gastric secretion on and off proton pump inhibitor treatment: a randomized double-blind controlled study in patients with gastro-esophageal reflux disease (GERD) and healthy subjects.
Steingoetter, A, Sauter, M, Curcic, J, Liu, D, Menne, D, Fried, M, Fox, M, Schwizer, W
BMC gastroenterology. 2015;:111
Abstract
BACKGROUND Postprandial accumulation of gastric secretions in the proximal stomach above the meal adjacent to the esophagogastric junction (EGJ), referred to as the 'acid pocket', has been proposed as a pathophysiological factor in gastro-esophageal reflux disease (GERD) and as a target for GERD treatment. This study assessed the effect of proton pump inhibitor (PPI) therapy on the volume, distribution and acidity of gastric secretions in GERD and healthy subjects (HS). METHODS A randomized, double blind, cross-over study in 12 HS and 12 GERD patients pre-treated with 40 mg pantoprazole (PPI) or placebo b.i.d. was performed. Postprandial secretion volume (SV), formation of a secretion layer and contact between the layer and the EGJ were quantified by Magnetic Resonance Imaging (MRI). Multi-channel pH-monitoring assessed intragastric pH. RESULTS A distinct layer of undiluted acid secretion was present on top of gastric contents in almost all participants on and off high-dose acid suppression. PPI reduced SV (193 ml to 100 ml, in HS, 227 ml to 94 ml in GERD; p < 0.01) and thickness of the acid layer (26 mm to 7 mm, 36 mm to 9 mm respectively, p < 0.01). No differences in secretion volume or layer thickness were observed between groups; however, off treatment, contact time between the secretion layer and EGJ was 2.6 times longer in GERD compared to HS (p = 0.012). This was not the case on PPI. CONCLUSIONS MRI can visualize and quantify the volume and distribution dynamics of gastric secretions that form a layer in the proximal stomach after ingestion of a liquid meal. The secretion volume and the secretion layer on top of gastric contents is similar in GERD patients and HS; however contact between the layer of undiluted secretion and the EGJ is prolonged in patients. High dose PPI reduced secretion volume by about 50% and reduced contact time between secretion and EGJ towards normal levels. TRIAL REGISTRATION NCT01212614.
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Noncoagulating Enteral Formula Can Empty Faster From the Stomach: A Double-Blind, Randomized Crossover Trial Using Magnetic Resonance Imaging.
Kuyumcu, S, Menne, D, Curcic, J, Goetze, O, Klebach, M, Abrahamse, E, Hofman, Z, Fried, M, Schwizer, W, Steingoetter, A
JPEN. Journal of parenteral and enteral nutrition. 2015;(5):544-51
Abstract
BACKGROUND The gastric accumulation of enteral formulas in tube-fed patients leads to an increased risk of vomiting and regurgitation. Gastric secretion-induced coagulation of proteins in enteral formulas might lead to gastric accumulation of solid protein particles that further increase the risk of upper digestive intolerance. This study used magnetic resonance imaging to noninvasively assess the half-emptying time (t50) of enteral formulas differing in protein composition. METHODS Three isocaloric (450 kcal) and isovolumetric (300 mL) enteral formulas, 1 with a noncoagulating P4 protein blend and 2 with coagulating casein-dominant protein blends, were compared in a double-blind, randomized, 3-way crossover study in 21 healthy volunteers. Gastric content emptying curves were fitted with the LinExp model to compute t50 and the parameter κ with κ > 1 reflecting the accumulation of gastric secretion. t50 and κ were compared between all 3 enteral formulas. The formula that emptied fastest was identified by an ordinal mixed model using the ranks of t50. RESULTS As indicated by values for κ > 1, all enteral formulas induced gastric secretion. No differences were detected for t50. However, the noncoagulating formula emptied fastest in 74% of all participants (P = .004). CONCLUSION This study demonstrates that a noncoagulating enteral formula can empty faster from the stomach compared with coagulating formulas in a large cohort of healthy volunteers. Investigations on the efficiency of the noncoagulating P4 protein blend in patients requiring tube feeding will further elucidate its potential for reducing upper digestive intolerance during enteral nutrition. Trial NTR2979.
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Imaging gastric structuring of lipid emulsions and its effect on gastrointestinal function: a randomized trial in healthy subjects.
Steingoetter, A, Radovic, T, Buetikofer, S, Curcic, J, Menne, D, Fried, M, Schwizer, W, Wooster, TJ
The American journal of clinical nutrition. 2015;(4):714-24
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BACKGROUND Efficient fat digestion requires fat processing within the stomach and fat sensing in the intestine. Both processes also control gastric emptying and gastrointestinal secretions. OBJECTIVE We aimed to visualize the influence of the intragastric stability of fat emulsions on their dynamics of gastric processing and structuring and to assess the effect this has on gastrointestinal motor and secretory functions. DESIGN Eighteen healthy subjects with normal body mass index (BMI) were studied on 4 separate occasions in a double-blind, randomized, crossover design. Magnetic resonance imaging (MRI) data of the gastrointestinal tract and blood triglycerides were recorded before and for 240 min after the consumption of the following 4 different fat emulsions: lipid emulsion 1 (LE1; acid stable, 0.33 μm), lipid emulsion 2 (LE2; acid stable, 52 μm), lipid emulsion 3 (LE3; acid unstable, solid fat, 0.32 μm), and lipid emulsion 4 (LE4; acid unstable, liquid fat, 0.38 μm). RESULTS Intragastric emulsion instability was associated with a change in gastric emptying. Acid-unstable emulsions exhibited biphasic and faster emptying profiles than did the 2 acid-stable emulsions (P ≤ 0.0001). When combined with solid fat (LE3), different dynamics of postprandial gallbladder volume were induced (P ≤ 0.001). For acid-stable emulsions, a reduction of droplet size by 2 orders of magnitude [LE1 (0.33 μm) compared with LE2 (52 μm)] delayed gastric emptying by 38 min. Although acid-stable (LE1 and LE2) and redispersible (LE4) emulsions caused a constant increase in blood triglycerides, no increase was detectable for LE3 (P < 0.0001). For LE3, MRI confirmed the generation of large fat particles during gastric processing, which emptied into and progressed through the small intestine. CONCLUSIONS MRI allows the detailed characterization of the in vivo fate of lipid emulsions. The acute effects of lipid emulsions on gastric emptying, gallbladder volume, and triglyceride absorption are dependent on microstructural changes undergone during consumption. Gastric peristalsis and secretion were effective at redispersing pools of liquid fat in the stomach. This trial was registered at clinicaltrials.gov as NCT01253005.
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Impact of a focused nutrition educational intervention coupled with improved access to fresh produce on purchasing behavior and consumption of fruits and vegetables in overweight patients with diabetes mellitus.
Weinstein, E, Galindo, RJ, Fried, M, Rucker, L, Davis, NJ
The Diabetes educator. 2014;(1):100-6
Abstract
PURPOSE The purpose of this study was to test the impact of distributing coupons redeemable at farmers markets plus an educational intervention on fruit and vegetable (F&V) purchase and consumption in overweight patients with type 2 diabetes (T2DM). METHODS Seventy-eight participants with T2DM being followed at Jacobi Medical Center, a large public hospital in the Bronx, New York, were randomized to receive the standard of care or a 1-hour session focused on benefits of F&V consumption and $6 in coupons. Questionnaires assessed demographics, F&V intake, and farmers market purchasing at baseline and 12 weeks. Clinical parameters were obtained through chart review at baseline and at 12 weeks. RESULTS Participants were predominantly Latino, females, and low income. At 12 weeks, there was a statistically significant increase in the number of participants in the intervention arm who reported purchasing from a farmers market. In addition, there was a minimal increase in fresh fruit intake in the intervention arm at 12 weeks. CONCLUSION Focused education combined with a small economic incentive resulted in an increase in purchasing behavior and fresh fruit intake per day. A more intense behavioral intervention combined with increased access may result in a significant impact on obesity and diabetes, particularly among low-income and racially diverse communities.
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Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa.
Taylor, SM, Antonia, AL, Harrington, WE, Goheen, MM, Mwapasa, V, Chaluluka, E, Fried, M, Kabyemela, E, Madanitsa, M, Khairallah, C, et al
Emerging infectious diseases. 2014;(7):1140-8
Abstract
Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance.
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Prevalence and presentation of lactose intolerance and effects on dairy product intake in healthy subjects and patients with irritable bowel syndrome.
Yang, J, Deng, Y, Chu, H, Cong, Y, Zhao, J, Pohl, D, Misselwitz, B, Fried, M, Dai, N, Fox, M
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2013;(3):262-268.e1
Abstract
BACKGROUND & AIMS The effects of lactase deficiency on digestive symptoms and diet in patients with irritable bowel syndrome (IBS) have not been well defined. We assessed lactose absorption and tolerance and the intake of dairy products in healthy volunteers (controls) and patients with diarrhea-predominant IBS (D-IBS). METHODS Sixty patients diagnosed with D-IBS at the Sir Run Run Shaw Hospital, Hangzhou, China and 60 controls were given hydrogen breath tests to detect malabsorption and intolerance after administration of 10, 20, and 40 g lactose in random order 7-14 days apart; participants and researchers were blinded to the dose. We assessed associations between the results and self-reported lactose intolerance (LI). RESULTS Malabsorption of 40 g lactose was observed in 93% of controls and 92% of patients with D-IBS. Fewer controls than patients with D-IBS were intolerant to 10 g lactose (3% vs 18%; odds ratio [OR], 6.51; 95% confidence interval [CI], 1.38-30.8; P = .008), 20 g lactose (22% vs 47%; OR, 3.16; 95% CI, 1.43-7.02; P = .004), and 40 g lactose (68% vs 85%; OR, 2.63; 95% CI, 1.08-6.42; P = .03). H(2) excretion was associated with symptom score (P = .001). Patients with D-IBS self-reported LI more frequently than controls (63% vs 22%; OR, 6.25; 95% CI, 2.78-14.0; P < .001) and ate fewer dairy products (P = .040). However, self-reported LI did not correlate with results from hydrogen breath tests. CONCLUSIONS The risk of LI is related to the dose of lactose ingested and intestinal gas production and is increased in patients with D-IBS. Self-reported LI, but not objective results from hydrogen breath tests, was associated with avoidance of dairy products.