Review of real-life teduglutide experience

Background: teduglutide is an agonist of glucagon-related peptide (aGLP2) effective as a treatment for patients with short bowel syndrome (SBS), an entity that affects quality of life, usually requires home parenteral nutrition (HPN) and generates significant health costs. The objective of the present narrative review was to assess the real-life experience reported with teduglutide.Methods and results: in real life, one meta-analysis and studies published with 440 patients indicate that Teduglutide is effective after the period of intestinal adaptation after surgery, reducing the need for HPN and in some cases even allowing it to be suspended. The response is heterogeneous, increasing progressively up to 2 years after the start of treatment and reaching 82 % in some series. The presence of colon in continuity is a negative predictor of early response, but a positive predictive factor for the withdrawal of HPN. The most common side effects are gastrointestinal in the early stages of treatment. There are late complications related to the stoma or the occurrence of colon polyps, although the frequency of the latter is very low. In adults, data on improved quality of life and cost-effectiveness are scarce.Conclusions: teduglutide is effective and safe and data from pivotal trials for the treatment of patients with SBS are confirmed in real life and can reduce or even stop HPN in some cases. Although it seems cost-effective, more studies are needed to identify those patients with the greatest benefit

Development and validation of a specific questionnaire to assess health-related quality of life in patients with home enteral nutrition: NutriQoL® development

Introduction: Home enteral nutrition (HEN) is indicated in patients with a functional gastrointestinal tract but who are unable to meet their nutritional requirements with normally consumed foodstuffs. HEN allows patients to remain in their social and family environment, thus reducing complications and costs associated with hospital admission, while increasing health-related quality of life (HRQoL). HRQoL in patients with HEN is mainly evaluated by generic instruments, which are not sensitive enough to identify certain specific patient-related outcomes of HEN. Objective: To develop a specific instrument to measure HRQoL in patients receiving HEN whose results allow interpretation regardless of the underlying disease and nutritional support administration route: the NutriQoL® questionnaire. Materials and methods: The development of the NutriQoL entailed a literature review, focus groups with experts, semistructured interviews with patients, an assessment of face validity and feasibility, and Rasch analysis conducted on data from a sample of 141 patients and 24 caregivers. Results: Of the 52 items initially proposed on the basis of the literature review, expert focus group, and semi-structured interviews with patients and caregivers, 17 items were finally selected through the development process to make up the final version of the NutriQoL, as well as a visual analog scale for global HRQoL scoring. The selected items were evaluated as adequate for frequency, importance, and clarity. Furthermore, they have been shown to be independent of the underlying condition and HEN administration route. Conclusion: A new instrument for measuring the HRQoL of patients with HEN in Spain has been developed, whose results are independent of the underlying condition and administration route. The next step will be the validation of the questionnaire to ensure that the instrument is valid, reliable, and sensitive to health status changes in patients, to be used periodically in usual clinical practice.The abstract of this paper was presented at the International Society for Pharmacoeconomics and Outcomes Research 17th Annual European Congress (Amsterdam, the Netherlands) on November 2014 as a poster with interim findings. The poster’s abstract was published in “Value in Health” Vol 17, Issue 7, A518 (http://www.valueinhealthjournal.com/article/S1098-3015(14)03541-4/pdf) and A575 (http://www.sciencedirect.com/science/article/pii/S1098301514038650). Nestlé Health Science sponsored the stud

Dynamic fronto-amygdalar interactions underlying emotion-regulation deficits in women at higher weight

Objective: The regulation of negative emotions entails the modulation of subcortical regions, such as the amygdala, by prefrontal regions. There is preliminary evidence suggesting that individuals at higher weight may present with hypoactivity in prefrontal regulatory systems during emotional regulation, although the directionality of these pathways has not been tested. In this study, we compared fronto-amygdalar effective connectivity during cognitive reappraisal as a function of BMI in 48 adult women with obesity and 54 control participants. Methods: Dynamic causal modeling and parametric empirical Bayes were used to map effective connectivity between the dorsomedial prefrontal cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and the amygdala. Results: Difficulty in Emotion Regulation Scale scores were higher in the obesity group compared with control participants (p < 0.001). A top-down cortical model best explained our functional magnetic resonance imaging data (posterior probability = 86%). Participants at higher BMI were less effective at inhibiting activity in the amygdala via the orbitofrontal cortex and dorsomedial prefrontal cortex during reappraisal compared with those at lower BMI. In contrast, increased excitatory modulation of dorsolateral prefrontal cortex-to-amygdalar connectivity was found in participants at lower BMI. Conclusions: These findings support a framework involving alterations in fronto-amygdalar connectivity contributing to difficulties in regulating negative affect in individuals at higher weight

Is Trabecular Bone Score Valuable In Bone Microstructure Assessment After Gastric Bypass In Women With Morbid Obesity?

Introduction: The effects of bariatric surgery on skeletal health raise many concerns. Trabecular bone score (TBS) is obtained through the analysis of lumbar spine dual X-ray absorptiometry (DXA) images and allows an indirect assessment of skeletal microarchitecture (MA). The aim of our study was to evaluate the changes in bone mineral density (BMD) and alterations in bone microarchitecture assessed by TBS in morbidly obese women undergoing Roux-en-Y gastric bypass (RYGB), over a three-year follow-up. Material/Methods: A prospective study of 38 morbidly obese white women, aged 46.3 +/- 8.2 years, undergoing RYGB was conducted. Biochemical analyses and DXA scans with TBS evaluation were performed before and at one year and three years after surgery. Results: Patients showed normal calcium and phosphorus plasma concentrations throughout the study. However, 25-hydroxyvitamin D (25(OH)D-3) decreased, and 71% of patients had a vitamin D deficiency at three years. BMD at femoral neck and lumbar spine (LSBMD) significantly decreased 13.53 +/- 5.42% and 6.03 +/- 6.79%, respectively, during the three-year follow-up; however Z-score values remained above those for women of the same age. TBS was within normal ranges at one and three years (1.431 +/- 106 and 1.413 +/- 85, respectively), and at the end of the study, 73.7% of patients had normal bone MA. TBS at three years correlated inversely with age (r = -0.41, p = 0.010), body fat (r = -0.465, p = 0.004) and greater body fat deposited in trunk (r = -0.48, p = 0.004), and positively with LSBMD (r = 0.433, p = 0.007), fat mass loss (r = 0.438, p = 0.007) and lean mass loss (r = 0.432, p = 0.008). In the regression analysis, TBS remained associated with body fat ( = -0.625, p = 0.031; R-2 = 0.47). The fracture risk, calculated by FRAX((R)) (University of Sheffield, Sheffield, UK), with and without adjustment by TBS, was low. Conclusion: Women undergoing RYGB in the mid-term have a preserved bone MA, assessed by TBS

Role of adipose tissue GLP-1R expression in metabolic improvement after bariatric surgery in patients with type 2 diabetes

We aimed to explore the relationship between GLP-1 receptor (GLP-1R) expression in adipose tissue (AT) and incretin secretion, glucose homeostasis and weight loss, in patients with morbid obesity and type 2 diabetes undergoing bariatric surgery. RNA was extracted from subcutaneous (SAT) and visceral (VAT) AT biopsies from 40 patients randomized to metabolic gastric bypass, sleeve gastrectomy or greater curvature plication. Biochemical parameters, fasting plasma insulin, glucagon and area under the curve (AUC) of GLP-1 following a standard meal test were determined before and 1 year after bariatric surgery. GLP-1R expression was higher in VAT than in SAT. GLP-1R expression in VAT correlated with weight (r = -0.453, p = 0.008), waist circumference (r = -0.494, p = 0.004), plasma insulin (r = -0.466, p = 0.007), and systolic blood pressure (BP) (r = -0.410, p = 0.018). At 1 year, GLP-1R expression in VAT was negatively associated with diastolic BP (r = -0.361, p = 0.039) and, following metabolic gastric bypass, with the increase of GLP-1 AUC, (R-2 = 0.46, p = 0.038). Finally, GLP-1R in AT was similar independently of diabetes outcomes and was not associated with weight loss after surgery. Thus, GLP-1R expression in AT is of limited value to predict incretin response and does not play a role in metabolic outcomes after bariatric surgery

Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (omega-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of omega-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-alpha (TNF-alpha), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of omega-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of omega-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) omega-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed

Long-term effects in bone mineral density after different bariatric procedures in patients with type 2 diabetes: outcomes of a randomized clinical trial

There is scant evidence of the long-term effects of bariatric surgery on bone mineral density (BMD). We compared BMD changes in patients with severe obesity and type 2 diabetes (T2D) 5 years after randomization to metabolic gastric bypass (mRYGB), sleeve gastrectomy (SG) and greater curvature plication (GCP). We studied the influence of first year gastrointestinal hormone changes on final bone outcomes. Forty-five patients, averaging 49.4 (7.8) years old and body mass index (BMI) 39.4 (1.9) kg/m(2), were included. BMD at lumbar spine (LS) was lower after mRYGB compared to SG and GCP: 0.89 [0.82;0.94] vs. 1.04 [0.91;1.16] vs. 0.99 [0.89;1.12],p= 0.020. A higher percentage of LS osteopenia was present after mRYGB 78.6% vs. 33.3% vs. 50.0%, respectively. BMD reduction was greater in T2D remitters vs. non-remitters. Weight at fifth year predicted BMD changes at the femoral neck (FN) (adjustedR(2): 0.3218;p= 0.002), and type of surgery (mRYGB) and menopause predicted BMD changes at LS (adjustedR(2): 0.2507;p< 0.015). In conclusion, mRYGB produces higher deleterious effects on bone at LS compared to SG and GCP in the long-term. Women in menopause undergoing mRYGB are at highest risk of bone deterioration. Gastrointestinal hormone changes after surgery do not play a major role in BMD outcomes

Treatment outcome of patients with comorbid type 1 diabetes and eating disorders

Background: Co-morbidity between Type 1 Diabetes Mellitus (T1DM) and eating disorders (ED) has been previously described; however the effect of this illness on the outcomes for conventional ED treatments has not been previously investigated. This study aims to compare clinical, psychopathological and personality features between two samples of ED individuals: those with comorbid T1DM and those without (No-DM); and to identify differences in treatment outcomes between the groups. Methods: This study compares treatment outcome, dropouts, ED psychopathology and personality characteristics for 20 individuals with ED and T1DM and 20 ED patients without diabetes, matched for diagnostic and treatment type. Results: The study found higher dropout rates from therapy in individuals with T1DM and worse treatment outcome in spite of having no significant differences in eating disorder psychopathology, although individuals with T1DM report misusing insulin. Conclusions: The low levels of motivation to change, and insulin abuse in T1DM patients, may suggest that treatment for patients with ED and T1DM should consider the individual's personality and role of insulin abuse when determining the appropriate intervention

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients

Introduction: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of omega-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral omega-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. Materials and methods: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of omega-3 fatty acids or a mixture of omega-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of omega-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion. The main objective is to determine whether 5 days administration of intravenous omega-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality. Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. Discussion: Studies of omega-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient