Impact of gastrointestinal symptoms and psychological disturbances on patients’ quality of life after restrictive or malabsorptive bariatric surgery / Impacto de los síntomas gastrointestinales y alteraciones psicológicas sobre la calidad de vida en los pacientes sometidos a cirugía bariátrica restrictiva o malabsortiva

Aim: The aim of this study was to evaluate and compare the presence and impact of Gastrointestinal (GI) symptoms, physical and psychological disturbances on patients’ QoL after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS). Methods: A prospective, observational, cross-sectional, comparative study was carried-out. GI symptoms and patients’ QoL were evaluated by the SF-36 questionnaire and the GI quality of life index (GIQLI). Correlation between GI symptoms, psychological disturbances and QoL scores was analysed. Results: 95 patients were included (mean age 50.5 years, range 22–70; 76 females). Presence of GI symptoms was a consistent finding in all patients, and postprandial fullness, abdominal distention and flatulence had a negative impact on patients’ QoL. Patients after SG showed a worsening of their initial psychological condition and the lowest QoL scores. Patients after RYGB showed the best GI symptoms-related QoL. Conclusions:Both restrictive and malabsorptive bariatric surgical procedures are associated with GI symptoms negatively affecting patients’ QoL. Compared to SG and BPD/DS, patients after RYGB showed the best GI symptoms-related QoL, which can be used as additional information to help in the clinical decision making of the bariatric procedure to be performed.(AU)

Objetivo: El objetivo de este estudio fue evaluar y comparar la presencia e impacto de los síntomas gastrointestinales (GI), los cambios físicos y psicológicos en la calidad de vida (CV) de los pacientes sometidos a tubulación gástrica (TG), bypass gástrico en Y de Roux (BGYR) y derivación biliopancreática con cruce duodenal (DBP/CD). Métodos: Se realizó un estudio prospectivo, observacional, transversal y comparativo. Los síntomas gastrointestinales y la CV de los pacientes fueron evaluados mediante el cuestionario SF-36 y el índice gastrointestinal de calidad de vida (GIQLI). Se analizó la relación entre los síntomas gastrointestinales, los trastornos psicológicos y las puntuaciones de CV. Resultados: Se incluyeron 95 pacientes (edad media: 50,5 años, rango: 22-70; 76 mujeres). La presencia de síntomas gastrointestinales fue un hallazgo constante en todos los pacientes, y la pesadez posprandial, la distensión abdominal y la flatulencia tuvieron un impacto negativo en la CV de los pacientes. Los pacientes después de la TG mostraron un empeoramiento de su estado psicológico inicial y unas puntuaciones más bajas en la CV. Los pacientes después del BGYR presentaron la mejor CV relacionada con los síntomas gastrointestinales. Conclusiones: Los procedimientos de cirugía bariátrica tanto restrictivos como malabsortivos se asocian a síntomas GI que afectan negativamente la CV de los pacientes. En comparación con la TG y la DBP/CD, los pacientes tras el BGYR presentaron la mejor CV relacionada con los síntomas GI, lo que puede utilizarse como información adicional para ayudar en la toma de decisiones clínicas sobre el procedimiento bariátrico a realizar.(AU)

Impact of gastrointestinal symptoms and psychological disturbances on patients' quality of life after restrictive or malabsorptive bariatric surgery.

AIM: The aim of this study was to evaluate and compare the presence and impact of Gastrointestinal (GI) symptoms, physical and psychological disturbances on patients' QoL after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS). METHODS: A prospective, observational, cross-sectional, comparative study was carried-out. GI symptoms and patients' QoL were evaluated by the SF-36 questionnaire and the GI quality of life index (GIQLI). Correlation between GI symptoms, psychological disturbances and QoL scores was analysed. RESULTS: 95 patients were included (mean age 50.5 years, range 22-70; 76 females). Presence of GI symptoms was a consistent finding in all patients, and postprandial fullness, abdominal distention and flatulence had a negative impact on patients' QoL. Patients after SG showed a worsening of their initial psychological condition and the lowest QoL scores. Patients after RYGB showed the best GI symptoms-related QoL. CONCLUSIONS: Both restrictive and malabsorptive bariatric surgical procedures are associated with GI symptoms negatively affecting patients' QoL. Compared to SG and BPD/DS, patients after RYGB showed the best GI symptoms-related QoL, which can be used as additional information to help in the clinical decision making of the bariatric procedure to be performed.

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention.

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague-Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.

Platelet Lipidome Fingerprint: New Assistance to Characterize Platelet Dysfunction in Obesity.

Obesity is associated with a pro-inflammatory and pro-thrombotic state that supports atherosclerosis progression and platelet hyper-reactivity. During the last decade, the platelet lipidome has been considered a treasure trove, as it is a source of biomarkers for preventing and treating different pathologies. The goal of the present study was to determine the lipid profile of platelets from non-diabetic, severely obese patients compared with their age- and sex-matched lean controls. Lipids from washed platelets were isolated and major phospholipids, sphingolipids and neutral lipids were analyzed either by gas chromatography or by liquid chromatography coupled to mass spectrometry. Despite a significant increase in obese patient's plasma triglycerides, there were no significant differences in the levels of triglycerides in platelets among the two groups. In contrast, total platelet cholesterol was significantly decreased in the obese group. The profiling of phospholipids showed that phosphatidylcholine and phosphatidylethanolamine contents were significantly reduced in platelets from obese patients. On the other hand, no significant differences were found in the sphingomyelin and ceramide levels, although there was also a tendency for reduced levels in the obese group. The outline of the glycerophospholipid and sphingolipid molecular species (fatty-acyl profiles) was similar in the two groups. In summary, these lipidomics data indicate that platelets from obese patients have a unique lipid fingerprint that may guide further studies and provide mechanistic-driven perspectives related to the hyperactivate state of platelets in obesity.

Human obese white adipose tissue sheds depot-specific extracellular vesicles and reveals candidate biomarkers for monitoring obesity and its comorbidities.

Extracellular vesicles (EVs) have been recently postulated as key players in metabolic disorders emerging as an alternative way of paracrine/endocrine communication. However, the nature of EVs shed by adipose tissue (AT) and their role in obesity is still very limited. Here, we isolated human morbid obese visceral (VAT) and subcutaneous (SAT) whole AT shed EVs from donors submitted to bariatric surgery to characterize their protein cargo by qualitative and quantitative/SWATH mass spectrometry analysis. We identified 574 different proteins shed by morbid obese VAT and 401 proteins in those from SAT, establishing the first obese AT EV proteome reference map. Only 50% of identified proteins in VAT vesicles were common to those in SAT; additionally, EVs shed by obese VAT showed more AT and obesity-related adipokines than SAT. Functional classification shows that obese VAT vesicles exhibit an enrichment of proteins implicated in AT inflammation and insulin resistance such as TGFBI, CAVN1, CD14, mimecan, thrombospondin-1, FABP-4 or AHNAK. Selected candidate biomarkers from the quantitative-SWATH analysis were validated in EVs from independent morbid obese and from moderate obese to lean individuals showing that morbid obese VAT vesicles are characterized by a diminution of syntenin 1 and the elevation of TGFBI and mimecan. Interestingly, TGFBI and mimecan containing vesicles could be detected and quantified at circulating level in plasma. Thus, a significant elevation of -TGFBI-EVs was detected on those obese patients with a history of T2D compared to nondiabetic, and an augmentation of mimecan-EVs in obese plasma compared to those in healthy lean individuals. Thus, we conclude that obese AT release functional EVs carrying AT and obesity candidate biomarkers which vary regarding the AT of origin. Our findings suggest that circulating EV-TGFBI may facilitate monitoring T2D status in obese patients, and EV-mimecan may be useful to track adiposity, and more precisely, visceral obesity.

Exocrine pancreatic function and dynamic of digestion after restrictive and malabsorptive bariatric surgery: a prospective, cross-sectional, and comparative study.

BACKGROUND: Gastrointestinal anatomical changes after restrictive and malabsorptive bariatric surgery lead to important disturbances in the process of digestion and absorption of nutrients and could lead to exocrine pancreatic insufficiency (EPI). OBJECTIVE: The aim of the present study was to evaluate and to compare pancreatic function and the dynamic of digestion and absorption of nutrients after restrictive and malabsorptive bariatric surgical procedures. SETTING: University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. METHODS: A prospective, observational, cross-sectional, comparative study of patients after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion with duodenal switch (BPD/DS) was carried out. Patients with obesity who did not undergo surgery were included as control group. Pancreatic function and the dynamic of digestion and absorption of nutrients were evaluated by the 13C-mixed triglyceride (13C-MTG) breath test. Six-hour 13C-cumulative recovery rate (13C-CRR), 13C exhalation peak, and 1-hour maximal 13C-CRR were calculated. RESULTS: One-hundred five patients were included (mean age, 49.8 yr; 84 women). Six-hour 13C-CRR was significantly reduced after BPD/DS (P < .001) but not after SG and RYGB. EPI was present in 75% of patients after BPD/DS, 8.3% of patients after RYGB, and 4.3% of patients after SG. Compared with the control group who did not undergo surgery, digestion and absorption of nutrients tended to occur earlier after SG, whereas it was delayed after RYGB and mainly after BPD/DS (P < .001). CONCLUSION: Bariatric surgery significantly alters the dynamic of the digestive process. EPI is very common after BPD/DS, frequent after RYGB, and less frequent after SG. This information is clinically relevant since EPI is a treatable condition associated with symptoms, nutritional deficiencies, and complications.

Conversion from Duodenal Switch to Single Anastomosis Duodenal Switch to Deal with Postoperative Malnutrition.

BACKGROUND: Duodenal switch (DS) is considered one of the most effective bariatric techniques for long-term weight and comorbidity control. After these operations, some patients may get severe complications related to malnutrition and a few of them may need surgical revision. Lengthening the common channel (CC) is usually the solution: changing the Roux anastomosis or with a side-to-side anastomosis (kissing X). We propose that when simplified construction of the DS is used, conversion to single anastomosis DS (SADI-S/OADS) is an easy and safe choice. OBJECTIVES: To evaluate the safety and effectiveness of conversion from DS to SADI-S in cases of malnutrition. METHODS: We report three patients with severe malnutrition after a DS at 9, 74, and 84 months. One of them had also liver failure related to alcohol abuse and malnutrition. Laparoscopic reoperations included a new ileo-ileal anastomosis and takedown of the Roux-en-Y anastomosis with the aim of lengthening the CC. RESULTS: All three patients were successfully converted by laparoscopy. After a median follow-up of 54.6 months [32-76 months], all of them had moderate weight regain and returned to normal biochemical nutritional parameters. Two patients with type 2 diabetes (T2DM) before DS had complete remission before conversion; one of them had recurrence of T2DM after conversion. The patient with liver failure improved significantly after conversion. CONCLUSIONS: Conversion from DS to SADI-S/OADS is a simple operation with excellent results in resolving malnutrition in those patients. However, weight regain and recurrence of comorbidities may arise.

Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity.

BACKGROUND/OBJECTIVES: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.

Phosphoproteomic Analysis of Platelets in Severe Obesity Uncovers Platelet Reactivity and Signaling Pathways Alterations.

OBJECTIVE: Obesity is associated with a proinflammatory and prothrombotic state that supports atherosclerosis progression. The goal of this study was to gain insights into the phosphorylation events related to platelet reactivity in obesity and identify platelet biomarkers and altered activation pathways in this clinical condition. Approach and Results: We performed a comparative phosphoproteomic analysis of resting platelets from obese patients and their age- and gender-matched lean controls. The phosphoproteomic data were validated by mechanistic, functional, and biochemical assays. We identified 220 differentially regulated phosphopeptides, from at least 175 proteins; interestingly, all were up-regulated in obesity. Most of the altered phosphoproteins are involved in SFKs (Src-family kinases)-related signaling pathways, cytoskeleton reorganization, and vesicle transport, some of them validated by targeted mass spectrometry. To confirm platelet dysfunction, flow cytometry assays were performed in whole blood indicating higher surface levels of GP (glycoprotein) VI and CLEC (C-type lectin-like receptor) 2 in platelets from obese patients correlating positively with body mass index. Receiver operator characteristics curves analysis suggested a much higher sensitivity for GPVI to discriminate between obese and lean individuals. Indeed, we also found that obese platelets displayed more adhesion to collagen-coated plates. In line with the above data, soluble GPVI levels-indicative of higher GPVI signaling activation-were almost double in plasma from obese patients. CONCLUSIONS: Our results provide novel information on platelet phosphorylation changes related to obesity, revealing the impact of this chronic pathology on platelet reactivity and pointing towards the main signaling pathways dysregulated.

Deciphering Adipose Tissue Extracellular Vesicles Protein Cargo and Its Role in Obesity.

The extracellular vesicles (EVs) have emerged as key players in metabolic disorders rising as an alternative way of paracrine/endocrine communication. In particular, in relation to adipose tissue (AT) secreted EVs, the current knowledge about its composition and function is still very limited. Nevertheless, those vesicles have been lately suggested as key players in AT communication at local level, and also with other metabolic peripheral and central organs participating in physiological homoeostasis, and also contributing to the metabolic deregulation related to obesity, diabetes, and associated comorbidities. The aim of this review is to summarize the most relevant data around the EVs secreted by adipose tissue, and especially in the context of obesity, focusing in its protein cargo. The description of the most frequent proteins identified in EVs shed by AT and its components, including their changes under pathological status, will give the reader a whole picture about the membrane/antigens, and intracellular proteins known so far, in an attempt to elucidate functional roles, and also suggesting biomarkers and new paths of therapeutic action.

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes.

Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

GLP1 Receptor Agonist and SGLT2 Inhibitor Combination: An Effective Approach in Real-world Clinical Practice.

PURPOSE: The aim of this study was to evaluate the effectiveness and safety of combination therapy with a sodium-glucose cotransporter-2 (SGLT2) inhibitor and a glucagon-like peptide-1 receptor agonist (GLP1RA) in patients with inadequately controlled type 2 diabetes. METHODS: A retrospective search of electronic prescriptions of patients undergoing GLP1RA and SGLT2 inhibitor combination therapy was conducted. Once the patients had been identified, demographic data, blood and urine analyses (glycosylated hemoglobin [HbA1c], glucose, renal function, albuminuria, lipid profile, liver enzymes, and uric acid), physical examination (weight, body mass index, and blood pressure), and adverse effects were obtained from their electronic clinical records according to each of the following 3 periods: before the initiation of the combination, the first visit after initiation, and the last available visit. The influence of the duration of diabetes and the drug combination sequence on the effectiveness of the treatment was also analyzed. Statistical analysis was performed with SPSS version 21.0 (IBM SPSS Statistics, IBM Corporation, Armonk, New York). Quantitative variables are presented as mean and SD and were compared by using the Student t test, one-way ANOVA, or repeated measures ANOVA with Bonferroni correction. Categorical variables are expressed as percentages and were compared by using the χ2 test. RESULTS: A total of 212 patients were included, with women accounting for 52.4%. The mean age (SD) of the population was 61.5 (9.6) years. A significant reduction in HbA1c (-12 mmol/mol [-1.1%]) was observed with combined therapy (P < 0.001). The target of HbA1c <53 mmol/mol (<7%) was achieved in 42% of the participants. Mean weight loss was -3.5 kg, and almost 40% of the patients attained the weight loss goal of ≥5% (P < 0.001 in all analyses). Transaminase levels and renal parameters also improved. These benefits persisted over time and bore no relation to the evolution of diabetes. Simultaneous initiation of a combination of a GLP1RA and SGLT2 inhibitor led to faster weight loss and a greater decrease in HbA1c than when they are used sequentially; however, the long-term benefits in terms of metabolic control were similar. Adverse events were rare, and a tendency for a reduced insulin dose was observed. IMPLICATIONS: The findings of this study reveal the combined benefits of a GLP1RA and SGLT2 inhibitor in real-world clinical practice. In general, the combined treatment was well tolerated, and few adverse events were detected.

Data on hyper-activation of GPVI signalling in obese patients: Towards the identification of novel antiplatelet targets in obesity.

This data article is associated with the manuscript "GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: elucidating potential anti-atherothrombotic targets in obesity" [1]. The study refers to a combination of different approaches in order to identify platelet-derived biomarkers in obesity. A total of 34 obese patients and their lean-matched controls were included in the study. We carried out a proteomic and functional (aggregation assays) analysis to find alterations in platelet-derived signalling pathways. After that, biochemical and mechanistic (flow cytometry assays) approaches were done in order to confirm a hyperactivation of the GPVI-related signalling pathway.

Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-ß are targets of the autoimmune response in type 1 diabetes.

Type 1 diabetes (T1D) results from the destruction of pancreatic ß-cells by the immune system, and CD8+ T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-ß. Previous work has shown increased proliferative responses to whole S100-ß in both human T1D patients and the nonobese diabetic (NOD) mouse model. We describe for the first time naturally processed and presented epitopes (NPPEs) presented by class I human leukocyte antigen-A*02:01 (A2.1) molecules derived from S100-ß. These NPPEs triggered IFN-γ responses more frequently in both newly diagnosed and long-term T1D patients compared with healthy donors. Furthermore, the same NPPEs are recognized during the autoimmune response leading to diabetes in A2.1-transgenic NOD mice as early as 4 wk of age. Interestingly, when these NPPEs are used to prevent diabetes in this animal model, an acceleration of the disease is observed together with an exacerbation in insulitis and an increase in S100-ß-specific cytotoxicity in vaccinated animals. Whether these can be used in diabetes prevention needs to be carefully evaluated in animal models before use in future clinical assays.-Calviño-Sampedro, C., Gomez-Tourino, I., Cordero, O. J., Reche, P. A., Gómez-Perosanz, M., Sánchez-Trincado, J. L., Rodríguez, M. Á., Sueiro, A. M., Viñuela, J. E., Calviño, R. V. Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-ß are targets of the autoimmune response in type 1 diabetes.

GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: Elucidating potential anti-atherothrombotic targets in obesity.

BACKGROUND AND AIMS: Platelets play a fundamental role in the increased atherothrombotic risk related to central obesity since they show hyperactivation and lower sensitivity to antiplatelet therapy in obese patients. The main goal of this study was to identify platelet biomarkers related to the risk of atherothrombosis in obese patients, confirm platelet activation levels in these patients, and identify altered activation pathways. METHODS: Platelets were obtained from cohorts of obese patients and age- and sex-matched lean controls. Biochemical and proteome analyses were done by two-dimensional differential in-gel electrophoresis (2D-DIGE), mass spectrometry, and immunoblotting. Functional and mechanistic studies were conducted with aggregation assays and flow cytometry. RESULTS: We confirmed an up-regulation of αIIb and fibrinogen isoforms in platelets from obese patients. A complementary platelet aggregation approach showed platelets from obese patients are hyper-reactive in response to collagen and collagen-related peptide (CRP), revealing the collagen receptor Glycoprotein VI (GPVI) signalling as one of the altered pathways. We also found the active form of Src (pTyr418) is up-regulated in platelets from obese individuals, which links proteomics to aggregation data. Moreover, we showed that CRP-activated platelets present higher levels of tyrosine phosphorylated PLCγ2 in obese patients, confirming alterations in GPVI signalling. In line with the above, flow cytometry studies show higher surface expression levels of total GPVI and GPVI-dimer in obese platelets, both correlating with BMI. CONCLUSIONS: Our results suggest a higher activation state of SFKs-mediated signalling pathways in platelets from obese patients, with a primary involvement of GPVI signalling.

A Combination of Proteomic Approaches Identifies A Panel of Circulating Extracellular Vesicle Proteins Related to the Risk of Suffering Cardiovascular Disease in Obese Patients.

Plasma-derived extracellular vesicles (EVs) have been extensively described as putative biomarkers in different diseases. Interestingly, increased levels of EVs subpopulations are well known to associate with obesity. The goal of this study is to identify EVs-derived biomarkers in plasma from obese patients in order to predict the development of pathological events associated with obesity. Samples are obtained from 22 obese patients and their lean-matched controls are divided into two cohorts: one for a 2D fluorescence difference gel electrophoresis (2D-DIGE)-based study, and the other one for a label free LC-MS/MS-based approach. EVs are isolated following a serial ultracentrifugation protocol. Twenty-two and 23 differentially regulated features are detected from 2D-DIGE and label free LC-MS/MS, respectively; most of them involve in the coagulation and complement cascades. Remarkably, there is an upregulation of complement C4, complement C3, and fibrinogen in obese patients following both approaches, the latter two also validated by 2D-western-blotting in an independent cohort. These results correlate with a proinflammatory and prothrombotic state of those individuals. On the other hand, a downregulation of adiponectin leading to an increased risk of suffering cardiovascular diseases has been shown. The results suggest the relevance of plasma-derived-EVs proteins as a source of potential biomarkers for the development of atherothrombotic events in obesity.

Epidemiology of home enteral nutrition: an approximation to reality.

INTRODUCTION: home enteral nutrition (HEN) has undergone an important development; however, there is a notable lack of information with regard to its incidence and characteristics. OBJECTIVES: our aim was to assess the state of HEN in our area. METHODS: an observational, prospective study, involving all patients who had initiated HEN in the Nutrition Unit during a year. Epidemiological, functional, and nutritional evolution of the patients was described and incidence of HEN was calculated. RESULTS: HEN incidences totalled 229/100,000 inhabitants/year. The HEN population in our area was characterized by the aged and a high frequency of comorbidity and functional limitations. Neurological and oncological diseases accounted for 50% of indications. The remaining cases were malnourished patients who had received short periods of HEN after hospitalization or a hip fracture. Oral supplements (60%) with standard and hypercaloric formulas were used the most. At baseline, 75% of the patients suffered from malnutrition. During the follow-up, patients showed weight gain (1.6%), an increase in the percentage of normal weight and overweight (from 74% to 82.7%, p = 0.001) and a reduction in pressure ulcers (15.7% vs10.3%, p < 0.001). The median duration of HEN was 8.5 months. Only a quarter of the patients experienced complications (mostly mild gastrointestinal complications); 43.1% had died at the end of the follow-up. CONCLUSIONS: in our area, the HEN incidence was much higher than those described in the literature. HEN appears to be a safe therapy with few complications that improves the nutritional status of the patients, even with short periods of administration.

Epidemiology of home enteral nutrition: an approximation to reality / Epidemiología de la nutrición enteral domiciliaria: una aproximación a la realidad

Introduction: home enteral nutrition (HEN) has undergone an important development; however, there is a notable lack of information with regard to its incidence and characteristics. Objectives: our aim was to assess the state of HEN in our area. Methods: an observational, prospective study, involving all patients who had initiated HEN in the Nutrition Unit during a year. Epidemiological, functional, and nutritional evolution of the patients was described and incidence of HEN was calculated. Results: HEN incidences totalled 229/100,000 inhabitants/year. The HEN population in our area was characterized by the aged and a high frequency of comorbidity and functional limitations. Neurological and oncological diseases accounted for 50% of indications. The remaining cases were malnourished patients who had received short periods of HEN after hospitalization or a hip fracture. Oral supplements (60%) with standard and hypercaloric formulas were used the most. At baseline, 75% of the patients suffered from malnutrition. During the follow-up, patients showed weight gain (1.6%), an increase in the percentage of normal weight and overweight (from 74% to 82.7%, p = 0.001) and a reduction in pressure ulcers (15.7% vs10.3%, p < 0.001). The median duration of HEN was 8.5 months. Only a quarter of the patients experienced complications (mostly mild gastrointestinal complications); 43.1% had died at the end of the follow-up. Conclusions: in our area, the HEN incidence was much higher than those described in the literature. HEN appears to be a safe therapy with few complications that improves the nutritional status of the patients, even with short periods of administration

Introducción: la nutrición enteral domiciliaria (NED) ha experimentado un importante desarrollo, aunque aún existe una notable carencia de información acerca de su incidencia y características. Objetivos: evaluar el estado de la NED en nuestra área. Métodos: estudio observacional y prospectivo que incluyó a todos los pacientes que iniciaron NED en el periodo de un año. Describimos su evolución epidemiológica, funcional y nutricional y calculamos la incidencia de NED. Resultados: la incidencia de NED alcanzó los 229/100.000 habitantes/año. La población con NED se caracterizó por ser añosa, con una elevada frecuencia de comorbilidad y limitación funcional. Las enfermedades neurológicas y oncológicas representaron el 50% de las indicaciones. El resto fueron pacientes malnutridos que recibieron periodos cortos de NED tras una hospitalización o fractura de cadera. Los suplementos orales con fórmulas estándar o hipercalóricas fueron los más utilizados (60%). Al inicio, el 75% de los pacientes tenía malnutrición. En el seguimiento, los pacientes lograron aumento de peso (1,6%) y mayor porcentaje de normopeso o sobrepeso (de 74% a 82,7%, p = 0,001). Las úlceras por presión se redujeron (15,7% vs. 10,3%, p < 0,001). La duración mediana de NED fue 8,5 meses. Solo una cuarta parte de los pacientes experimentaron complicaciones, la mayoría de ellas gastrointestinales y leves. El 43,1% había fallecido al final del seguimiento. Conclusiones: en nuestra área, la incidencia de NED es más elevada respecto a lo descrito en la literatura. La NED es un tratamiento seguro con pocas complicaciones que mejora el estado nutricional de los pacientes, incluso con periodos cortos de administración

ECONOMIC BURDEN OF HOME ARTIFICIAL NUTRITION IN THE HEALTH AREA OF SANTIAGO DE COMPOSTELA.

INTRODUCTION: home artificial nutrition (HAN) is a growing therapy, but the absence of obligatory registries complicates the calculation of its real economic burden. The aim of this study was to assess the state and economic impact of HAN in our health area. METHODS: an observational, prospective study was designed to calculate the cost of nutritional formulas and materials in patients who initiated HAN in the nutrition unit during a year. RESULTS: we included 573 new patients with HAN during the study period, 60% of whom were treated with oral supplements. The median daily cost of oral HAN was 3.65 (IQR 18.63) euros compared to a cost of 8.86 (IQR 20.02) euros for enteral-access HAN. The daily expenditure per 1 000 kcal of diet was higher for patients on oral HAN than for patients with tubes (5.13 vs. 4.52 euros, p < 0.001). The median cost of the complete HAN treatments during the study period was also calculated (186.60 euros and 531.99 euros for oral and tube HAN, respectively). The total estimated cost for all patients who initiated HAN in the study period was around one million euros. CONCLUSIONS: HAN represented an important economic burden in our health area, but the estimated daily cost of HAN was moderate, probably because of the high frequency of oral HAN, the adjusted treatments, and the centralized dispensation by the hospital pharmacy.

Introducción: la nutrición artificial domiciliaria (NAD) es una terapia en creciente desarrollo, pero la ausencia de registros obligatorios hace difícil calcular la carga económica que implica. Nuestro objetivo es evaluar el estado y el impacto económico de la NAD en nuestra área sanitaria. Métodos: estudio observacional y prospectivo diseñado para estimar el gasto en fórmulas y materiales nutricionales en los pacientes que iniciaron NAD durante 1 año. Resultados: se incluyeron 573 pacientes que iniciaron NAD en el período de estudio. El 60% recibieron suplementos orales. La mediana de gasto diario fue de 3,65 (RIC 18,63) euros en la NAD oral y de 8,86 (RIC 20,02) euros en la NAD por acceso enteral. El gasto por 1.000 kcal de dieta fue superior en los pacientes con NAD oral respecto a los pacientes con NAD enteral (5,13 vs. 4,52 euros, p < 0.001). Asimismo se calculó la mediana de gasto completo de los tratamientos durante todo el período de estudio (186,60 euros y 531,99 euros en NAD oral y enteral, respectivamente). Considerando el gasto conjunto de todos los pacientes que iniciaron NAD en el período de estudio, el gasto estimado estaría en torno a un millón de euros. Conclusiones: la NAD representa una importante carga económica en nuestra área sanitaria. Sin embargo, el gasto diario estimado fue moderado, probablemente por la elevada proporción de NAD oral en nuestra muestra, la revisión frecuente de la indicación y la centralización de la dispensación desde el servicio de Farmacia Hospitalaria.

Economic burden of home artificial nutrition in the health area of Santiago de Compostela / Impacto económico de la nutrición artificial domiciliaria en el área sanitaria de Santiago de Compostela

Introduction: home artificial nutrition (HAN) is a growing therapy, but the absence of obligatory registries complicates the calculation of its real economic burden. The aim of this study was to assess the state and economic impact of HAN in our health area. Methods: an observational, prospective study was designed to calculate the cost of nutritional formulas and materials in patients who initiated HAN in the nutrition unit during a year. Results: we included 573 new patients with HAN during the study period, 60% of whom were treated with oral supplements. The median daily cost of oral HAN was 3.65 (IQR 18.63) euros compared to a cost of 8.86 (IQR 20.02) euros for enteral-access HAN. The daily expenditure per 1 000 kcal of diet was higher for patients on oral HAN than for patients with tubes (5.13 vs. 4.52 euros, p <0.001). The median cost of the complete HAN treatments during the study period was also calculated (186.60 euros and 531.99 euros for oral and tube HAN, respectively). The total estimated cost for all patients who initiated HAN in the study period was around one million euros. Conclusions: HAN represented an important economic burden in our health area, but the estimated daily cost of HAN was moderate, probably because of the high frequency of oral HAN, the adjusted treatments, and the centralized dispensation by the hospital pharmacy (AU)

Introducción: la nutrición artificial domiciliaria (NAD) es una terapia en creciente desarrollo, pero la ausencia de registros obligatorios hace difícil calcular la carga econó- mica que implica. Nuestro objetivo es evaluar el estado y el impacto económico de la NAD en nuestra área sanitaria. Métodos: estudio observacional y prospectivo diseñado para estimar el gasto en fórmulas y materiales nutricionales en los pacientes que iniciaron NAD durante 1 año. Resultados: se incluyeron 573 pacientes que iniciaron NAD en el período de estudio. El 60% recibieron suplementos orales. La mediana de gasto diario fue de 3,65 (RIC 18,63) euros en la NAD oral y de 8,86 (RIC 20,02) euros en la NAD por acceso enteral. El gasto por 1.000 kcal de dieta fue superior en los pacientes con NAD oral respecto a los pacientes con NAD enteral (5,13 vs. 4,52 euros, p<0.001). Asimismo se calculó la mediana de gasto completo de los tratamientos durante todo el período de estudio (186,60 euros y 531,99 euros en NAD oral y enteral, respectivamente). Considerando el gasto conjunto de todos los pacientes que iniciaron NAD en el período de estudio, el gasto estimado estaría en torno a un millón de euros. Conclusiones: la NAD representa una importante carga económica en nuestra área sanitaria. Sin embargo, el gasto diario estimado fue moderado, probablemente por la elevada proporción de NAD oral en nuestra muestra, la revisión frecuente de la indicación y la centralización de la dispensación desde el servicio de Farmacia Hospitalaria (AU)