Publications by authors named "Assumpta Caixàs"

59 Publications

Altered Gesture Imitation and Brain Anatomy in Adult Prader-Willi Syndrome Patients.

J Int Neuropsychol Soc 2021 Mar 4:1-13. Epub 2021 Mar 4.

Specialized Service in Mental Health and Intellectual Disability Department, Institut Assistència Sanitària (IAS), Parc Hospitalari Martí i Julià, Girona, Spain.

Objective: To explore motor praxis in adults with Prader-Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements.

Method: Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis.

Results: Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas.

Conclusions: Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.
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http://dx.doi.org/10.1017/S1355617721000060DOI Listing
March 2021

Influence of the BDNF Val66Met polymorphism on weight loss after bariatric surgery: a 24-month follow-up.

Surg Obes Relat Dis 2021 Jan 27;17(1):185-192. Epub 2020 Aug 27.

Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain; Centre for Biomedical Research Network on Mental Health, Instituto de Salud Carlos III, Barcelona, Spain. Electronic address:

Background: Bariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery.

Objectives: To examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity.

Setting: University hospital in Spain.

Methods: The present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated.

Results: Longitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D.

Conclusion: Our data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect.
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http://dx.doi.org/10.1016/j.soard.2020.08.012DOI Listing
January 2021

The SEEN comprehensive clinical survey of adult obesity: Executive summary.

Endocrinol Diabetes Nutr 2021 Feb 12;68(2):130-136. Epub 2020 Sep 12.

Servicio de Endocrinología y Nutrición, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Gregorio Marañón, Madrid, España.

Obesity is one of the great challenges in healthcare nowadays with important implications for health so requiring comprehensive management. This document aims to establish practical and evidence-based recommendations for the diagnosis and management of in Spain, from the perspective of the clinical endocrinologist. A position statement has been made that can be consulted at www.seen.es, and that has been agreed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), together with the Nutrition Area (NutriSEEN) and the Working Group of Endocrinology, Nutrition and Physical Exercise (GENEFSEEN).
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http://dx.doi.org/10.1016/j.endinu.2020.05.003DOI Listing
February 2021

Longitudinal changes in telomere length in a cohort of obese patients submitted to bariatric surgery: a 2-year follow-up.

Surg Obes Relat Dis 2020 Nov 27;16(11):1794-1801. Epub 2020 Jun 27.

Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain; Centre for Biomedical Research Network on Mental Health, Instituto de Salud Carlos III, Barcelona, Spain. Electronic address:

Background: Telomere length (TL) is one biomarker of cell aging used to explore the effects of the environment on age-related pathologies. Obesity and high body mass index have been identified as a risk factors for shortened TL.

Objective: To evaluate TL in different subtypes of obese patients, and to examine changes in TL in relation to weight loss after bariatric surgery.

Setting: University Hospital in Spain.

Methods: A cohort of 94 patients submitted to bariatric surgery were followed-up during 24 months (t: lost to follow-up = 0%). All patients were evaluated before surgery (t) and during the postoperative period (t, t, and t) for body mass index and metabolic variables. We assessed TL at each timepoint using quantitative polymerase chain reactions and the telomere sequence to single-copy gene sequence ratio method.

Results: Patients with class III obesity showed significantly shorter TL at baseline than those patients with class II obesity (P = .027). No differences in TL were found between patients with or without type 2 diabetes or metabolic syndrome. Longitudinal analysis did not show an effect of time, type of surgery, age, or sex on TL. However, a generalized estimating equation model showed that TL was shorter amongst class III obesity patients across the time course (P = .008). Comparison between patients with obesity class II and class III showed differences in TL at t (adjusted P = .024), whereby class II patients had longer TL. However, no difference was observed at the other evaluated times.

Conclusion: Obesity severity may have negative effects on TL independently of type 2 diabetes or metabolic syndrome. Although TL is significantly longer in class II obesity patients relative to class III 6 months after bariatric surgery. This difference is not apparent after 24 months.
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http://dx.doi.org/10.1016/j.soard.2020.06.027DOI Listing
November 2020

Response to the letter to the editor: FKBP5 polymorphism rs1360780 and weight loss after bariatric surgery.

Surg Obes Relat Dis 2020 07 1;16(7):974-975. Epub 2020 Apr 1.

Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona, Spain; Centre for Biomedical Research Network on Mental Health, Instituto de Salud Carlos III, Barcelona, Spain.

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http://dx.doi.org/10.1016/j.soard.2020.03.026DOI Listing
July 2020

New Metrics to Assess Type 2 Diabetes After Bariatric Surgery: The "Time-Within-Remission Range".

J Clin Med 2020 Apr 9;9(4). Epub 2020 Apr 9.

Hospital Universitario San Cecilio, 18016 Granada, Spain.

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the "time-within-remission range" as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, "time-within-remission range" and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m) underwent primary bariatric procedures. "Time-within-remission range" were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques ( < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the "time-within-remission range". The association of bariatric techniques with "time-within-remission range", using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The "time-within-remission range" unveils a superiority of gastric bypass compared to sleeve gastrectomy.
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http://dx.doi.org/10.3390/jcm9041070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230819PMC
April 2020

Central Adrenal Insufficiency Is Rare in Adults With Prader-Willi Syndrome.

J Clin Endocrinol Metab 2020 07;105(7)

Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Context: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension-already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity-or even mortality.

Objective: To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT).

Design: Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645).

Setting: Outpatient clinic.

Patients Or Other Participants: Eighty-two adults with genetically confirmed PWS.

Main Outcome Measure: For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient.

Results: Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism.

Conclusions: Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS.
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http://dx.doi.org/10.1210/clinem/dgaa168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211032PMC
July 2020

SEEDO-SEMERGEN consensus document on continuous care of obesity between Primary Care and Specialist Hospital Units 2019.

Med Clin (Barc) 2020 09 17;155(6):267.e1-267.e11. Epub 2020 Feb 17.

Sociedad Española de Obesidad (SEEDO), España; Servicio de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, España; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), España.

The high prevalence of obesity in our environment, a chronic disease of complex management and responsible for multiple comorbidities, requires the implementation of coordination strategies in clinical care between primary care and specialist hospital units. In a cross-sectional care model, primary care physicians guide all therapeutic management related to obesity. Together with them, specialists in endocrinology and nutrition and other health staff help to form a functional unit that focuses on obesity. The main goal of this document is to improve the coordination between care levels, to optimize resources, avoid patients' unrealistic expectations and improve patient follow-up after discharge from hospital.
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http://dx.doi.org/10.1016/j.medcli.2019.10.014DOI Listing
September 2020

Synovial Adiponectin Was More Associated with Clinical Severity than Synovial Leptin in Women with Knee Osteoarthritis.

Cartilage 2020 Feb 20:1947603520904776. Epub 2020 Feb 20.

Rheumatology Department, Parc Taulí University Hospital, Sabadell, Barcelona, Spain.

Objective: Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis.

Design: Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum.

Results: Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control.

Conclusions: Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.
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http://dx.doi.org/10.1177/1947603520904776DOI Listing
February 2020

Role of the FKBP5 polymorphism rs1360780, age, sex, and type of surgery in weight loss after bariatric surgery: a follow-up study.

Surg Obes Relat Dis 2020 Apr 16;16(4):581-589. Epub 2019 Dec 16.

Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain; Centre for Biomedical Research Network on Mental Health, Instituto de Salud Carlos III, Barcelona, Spain. Electronic address:

Background: Emerging evidence suggests that the FK506 binding protein 51 (FKBP5/FKBP51), encoded by the FKBP5 gene, influences weight and metabolic regulation. The T allele of a functional polymorphism in FKBP5 (rs1360780), has been associated with the expression of FKBP51 and weight loss after bariatric surgery.

Objective: To examine the role of the FKBP5 rs1360780 polymorphism in relation to age, sex, and type of surgery in weight loss after bariatric surgery in patients with severe obesity.

Setting: University Hospital in Spain METHODS: A cohort of 151 obese patients submitted to Roux-en-Y gastric bypass (62.3%) and sleeve gastrectomy (37.7%) were followed-up during 24-months (t; loss to follow-up: 0%). During the postoperative period body mass index (BMI) and percentage of excess and total weight loss were evaluated.

Results: The BMI analysis showed an effect of the interaction FKBP5 genotype by sex (P = .0004) and a tendency to the interaction genotype by surgery (P = .048), so that men carrying the T allele had higher BMI at t than those without the T allele, and T-allele carriers that underwent sleeve gastrectomy had higher BMI at t than the noncarriers. Additionally, we found an interaction between FKBP5 and age for the percentage of excess weight loss and BMI (P = .0005 and P = 1.5e-7, respectively), whereby individuals >48 years with the T allele displayed significant differences for the analyzed variables at t compared with the homozygotes for the alternate C allele showing lower weight loss.

Conclusion: FKBP5 rs1360780 genotype has specific effects on weight loss outcomes after bariatric surgery depending on sex, age, and type of surgery, suggesting worse results in older males carrying the T allele who have undergone sleeve gastrectomy.
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http://dx.doi.org/10.1016/j.soard.2019.12.002DOI Listing
April 2020

Review of the management of diarrhea syndrome after a bariatric surgery.

Endocrinol Diabetes Nutr 2020 Jun - Jul;67(6):401-407. Epub 2019 Dec 13.

Unidad de Gastroenterología, Servicio de Aparato Digestivo, Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, España.

Obesity is a prevalent health problem in our population. Bariatric surgery is the indicated treatment for severe cases. It is very effective (together with an adequate lifestyle modification) but it is also associated with frequent adverse events. One of the most frequent and disturbing adverse event is diarrhea. Diarrhea after bariatric surgery may be secondary to multiple causes and the physiopathogenic mechanisms may depend on the type of surgery performed. The most frequent diarrhea mechanisms are dumping syndrome, vagotomy, short bowel syndrome, carbohydrate malabsorption, protein malabsorption, alterations of the microbiota, Clostridium difficile infection, bacterial overgrowth, bile salt malabsorption, pancreatic insufficiency, endocrinological disorders, addictive disorders, and other digestive disorders not necessarily related to surgery.
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http://dx.doi.org/10.1016/j.endinu.2019.09.013DOI Listing
December 2019

Simultaneous onset of type 1 diabetes mellitus and silent thyroiditis under durvalumab treatment

Endocrinol Diabetes Metab Case Rep 2019 Jul 15;2019(1). Epub 2019 Jul 15.

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Sabadell, Barcelona, Spain

Summary: Durvalumab, a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules, is increasingly used in advanced neoplasias. Durvalumab use is associated with increased immune-related adverse events. We report a case of a 55-year-old man who presented to our emergency room with hyperglycaemia after receiving durvalumab for urothelial high-grade non-muscle-invasive bladder cancer. On presentation, he had polyuria, polyphagia, nausea and vomiting, and laboratory test revealed diabetic ketoacidosis (DKA). Other than durvalumab, no precipitating factors were identified. Pre-durvalumab blood glucose was normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. Simultaneously, he presented a thyroid hormone pattern that evolved in 10 weeks from subclinical hyperthyroidism (initially attributed to iodinated contrast used in a previous computerised tomography) to overt hyperthyroidism and then to severe primary hypothyroidism (TSH: 34.40 µU/mL, free thyroxine (FT4): <0.23 ng/dL and free tri-iodothyronine (FT3): 0.57 pg/mL). Replacement therapy with levothyroxine was initiated. Finally, he was tested positive for anti-glutamic acid decarboxylase (GAD65), anti-thyroglobulin (Tg) and antithyroid peroxidase (TPO) antibodies (Abs) and diagnosed with type 1 diabetes mellitus (DM) and silent thyroiditis caused by durvalumab. When durvalumab was stopped, he maintained the treatment of multiple daily insulin doses and levothyroxine. Clinicians need to be alerted about the development of endocrinopathies, such as DM, DKA and primary hypothyroidism in the patients receiving durvalumab.

Learning Points: Patients treated with anti-PD-L1 should be screened for the most common immune-related adverse events (irAEs). Glucose levels and thyroid function should be monitored before and during the treatment. Durvalumab is mainly associated with thyroid and endocrine pancreas dysfunction. In the patients with significant autoimmune background, risk–benefit balance of antineoplastic immunotherapy should be accurately assessed.
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http://dx.doi.org/10.1530/EDM-19-0045DOI Listing
July 2019

Longitudinal changes of microbiome composition and microbial metabolomics after surgical weight loss in individuals with obesity.

Surg Obes Relat Dis 2019 Aug 10;15(8):1367-1373. Epub 2019 Jun 10.

New York Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York. Electronic address:

Background: Some of the metabolic effects of bariatric surgery may be mediated by the gut microbiome.

Objectives: To study the effect of bariatric surgery on changes to gut microbiota composition and bacterial pathways, and their relation to metabolic parameters after bariatric surgery.

Settings: University hospitals in the United States and Spain.

Methods: Microbial diversity and composition by 16 S rRNA sequencing, putative bacterial pathways, and targeted circulating metabolites were studied in 26 individuals with severe obesity, with and without type 2 diabetes, before and at 3, 6, and 12 months after either gastric bypass or sleeve gastrectomy.

Results: Bariatric surgery tended to increase alpha diversity, and significantly altered beta diversity, microbiota composition, and function up to 6 months after surgery, but these changes tend to regress to presurgery levels by 12 months. Twelve of 15 bacterial pathways enriched after surgery also regressed to presurgery levels at 12 months. Network analysis identified groups of bacteria significantly correlated with levels of circulating metabolites over time. There were no differences between study sites, surgery type, or diabetes status in terms of microbial diversity and composition at baseline and after surgery.

Conclusions: The association among changes in microbiome with decreased circulating biomarkers of inflammation, increased bile acids, and products of choline metabolism and other bacterial pathways suggest that the microbiome partially mediates improvement of metabolism during the first year after bariatric surgery.
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http://dx.doi.org/10.1016/j.soard.2019.05.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722012PMC
August 2019

Assessing Motivational Stages and Processes of Change for Weight Management Around Bariatric Surgery: a Multicenter Study.

Obes Surg 2019 10;29(10):3348-3356

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

Introduction/purpose: The assessment of the patients' motivation as a predictor of behavioral change via five stages (pre-contemplation, contemplation, preparation, action, and maintenance) and four processes (emotional re-evaluation, weight management actions, environmental restructuring, and weight consequences evaluation) of change.

Materials/methods: A total of 542 participants (251 waiting for bariatric surgery (BS), 90 undergoing BS, and 201 controls) completed the Stages (S-Weight) and Processes (P-Weight) of Change in Overweight and Obese People questionnaires in a multicenter cross-sectional study.

Results: A higher percentage of subjects seeking BS (31.7%) were in the action stage (16.7% of post-BS patients, p < 0.001; 14.9% of controls, p < 0.001). The referred body mass index (BMI) reduction was higher in subjects in active stages (3.6 ± 4.4 kg/m in maintenance versus 1.4 ± 1.4 kg/m in contemplation, p < 0.001). In the P-Weight questionnaire, patients looking for BS scored significant higher in the four processes of change than controls. In addition, a positive and significantly correlation between BMI and the four processes was observed. In the stepwise multivariate analysis, BMI and the S-Weight allocation were constantly associated with the four processes of change.

Conclusion: Obesity is accompanied by a modifying behavioral stage, suggesting that subjects before BS are seriously thinking about overcoming excess weight. To identify subjects on the waiting list for BS who will be more receptive to weight lost interventions remains a challenge.
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http://dx.doi.org/10.1007/s11695-019-04001-4DOI Listing
October 2019

Psychopathological disorders in Prader-Willi syndrome.

Endocrinol Diabetes Nutr 2019 Nov 18;66(9):579-587. Epub 2019 Apr 18.

Servicio de Endocrinología y Nutrición, Hospital Universitari Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España. Electronic address:

Prader-Willi syndrome is a genetic disorder caused by chromosomal changes in segment 15q11-q13 including cognitive, mental, and behavioral symptoms, as well as a specific physical phenotype. Both the most common psychopathological changes (intellectual disability, obsessions, impulsivity, autism spectrum disorders, self-injuries) and the main psychiatric comorbidities (affective disorders, psychosis, obsessive-compulsive disorder, autism spectrum disorder) are characterized by a great heterogeneity, which warrants the need for better identification of their frequency and clinical signs. In addition to its effects on body compositionand hypotony, growth hormone has been shown to be useful for regulating patient behavior, and psychoactive drugs are also an option. Other alternatives have shown promising results in experimental trials. Adequate understanding of the psychopathology associated to Prader-Willi syndrome would allow for improving clinical approach, symptom identification, detection of comorbidities, and administration of more effective treatments, leading to better clinical outcomes.
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http://dx.doi.org/10.1016/j.endinu.2019.03.004DOI Listing
November 2019

Lack of response to disgusting food in the hypothalamus and related structures in Prader Willi syndrome.

Neuroimage Clin 2019 4;21:101662. Epub 2019 Jan 4.

Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT- UAB, 08208 Sabadell, Spain.

Objective: To investigate, based on a putative abnormal neural processing of disgusting signals in Prader Willi syndrome (PWS) patients, the brain response to visual representations of disgusting food in PWS using functional MRI (fMRI).

Methods: Twenty-one genetically-confirmed PWS patients, 30 age- and sex-matched and 28 BMI-matched control subjects viewed a movie depicting disgusting food-related scenes interspersed with scenes of appetizing food while fMRI was acquired. Brain activation maps were compared between groups and correlated with disgust and hunger ratings.

Results: At the cortical level, the response to disgusting food representations in PWS patients was qualitatively similar to that of control subjects, albeit less extensive, and engaged brain regions typically related to visually-evoked disgust, such as the anterior insula/frontal operculum, the lateral frontal cortex and visual areas. By contrast, activation was almost absent in limbic structures directly concerned with the regulation of instinctive behavior robustly activated in control subjects, such as the hypothalamus, amygdala/hippocampus and periaqueductal gray.

Conclusions: Our study provides novel insights into the neural substrates of appetite control in a genetically-mediated cause of obesity. The presence of significant cortical changes further indicates that PWS patients consciously process disgusting stimuli, but the virtual absence of response in deep, limbic structures suggests that disgusting signals do not adequately reach the primary brain system for the appetite control.
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http://dx.doi.org/10.1016/j.nicl.2019.101662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412080PMC
January 2020

Outcomes of Bariatric Surgery in Patients with Cirrhosis.

Obes Surg 2019 02;29(2):585-592

Department of Endocrinology and Nutrition, Parc Taulí University Hospital, UAB, Sabadell, Spain.

Context: Information concerning the risk-benefit profile of bariatric surgery in subjects with liver cirrhosis is scarce. Our aim was to describe the long-term outcomes of bariatric surgery in a cohort of patients with liver cirrhosis submitted to bariatric surgery.

Methods: This was a multicenter, retrospective observational study performed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), with a review of patients with cirrhosis who had undergone bariatric surgery during the period from April 2004 to March 2017 in ten public reference hospitals in Spain.

Results: Data on 41 patients with cirrhosis submitted to obesity surgery were collected (mean age 53.8 ± 7.9 years, 46.3% women, presurgical BMI 45 ± 8.3 kg/m). All but one patient belonged to Child-Pugh class A, and sleeve gastrectomy was conducted in 68.3% of cases. Percentage of total weight loss (%TWL) was 26.33 ± 8.3% and 21.16 ± 15.32% at 1 and 5 years after surgery, respectively. This was accompanied by a significant reduction of type 2 diabetes, high blood pressure, and dyslipidemia and by an improvement of liver enzymes over time. Model for End-Stage Liver Disease (MELD) index increased from 7.2 ± 1.9 to 9.8 ± 4.6 after 5 years. Seven patients (17%) developed early postsurgical complications. No postsurgical mortality was observed. During follow-up, only five patients developed liver decompensation.

Conclusions: Bariatric surgery in selected patients with liver cirrhosis has metabolic benefits that could have a positive impact on liver prognosis.

Trial Registration: Controlledtrials.com Identifier: 10.1186/ISRCTN15009106.
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http://dx.doi.org/10.1007/s11695-018-3562-8DOI Listing
February 2019

Kallmann syndrome and ichthyosis: a case of contiguous gene deletion syndrome.

Endocrinol Diabetes Metab Case Rep 2017 Sep 28;2017. Epub 2017 Sep 28.

Endocrinology Department, Parc Taulí University Hospital, Sabadell, Barcelona, Spain.

Kallmann syndrome is a genetically heterogeneous form of hypogonadotropic hypogonadism caused by gonadotropin-releasing hormone deficiency and characterized by anosmia or hyposmia due to hypoplasia of the olfactory bulbs; osteoporosis and metabolic syndrome can develop due to longstanding untreated hypogonadism. Kallmann syndrome affects 1 in 10 000 men and 1 in 50 000 women. Defects in 17 genes, including KAL1, have been implicated. Kallmann syndrome can be associated with X-linked ichthyosis, a skin disorder characterized by early onset dark, dry, irregular scales affecting the limb and trunk, caused by a defect of the steroid sulfatase gene (STS). Both KAL1 and STS are located in the Xp22.3 region; therefore, deletions in this region cause a contiguous gene syndrome. We report the case of a 32-year-old man with ichthyosis referred for evaluation of excessive height (2.07 m) and weight (BMI: 29.6 kg/m2), microgenitalia and absence of secondary sex characteristics. We diagnosed Kallmann syndrome with ichthyosis due to a deletion in Xp22.3, a rare phenomenon. Learning points: Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism with anosmia or hyposmia associated with defects in the production or action of gonadotropin-releasing hormone (GnRH) and hypoplasia of the olfactory bulbs. Several genes have been implicated in Kallmann syndrome, including KAL1, located in the Xp22.3 region, which is responsible for X-linked Kallmann syndrome. KAL1 encodes the protein anosmin-1. X-linked ichthyosis is caused by deficiency of the steroid sulfatase enzyme, encoded by STS, which is also located in the Xp22.3 region. Deletions involving this region can affect both genes and result in contiguous gene syndromes. Phenotype can guide clinicians toward suspicion of a specific genetic mutation. KAL1 mutations are mostly related to microgenitalia, unilateral renal agenesis and synkinesia, although patients need not present all these abnormalities. Longstanding untreated hypogonadism is associated with poor sexual health, osteoporosis and metabolic syndrome with the concomitant risk of developing type 2 diabetes mellitus and obesity. Treatment aims to promote the development of secondary sex characteristics, build and sustain normal bone and muscle mass and restore fertility. Treatment can also help minimize some psychological consequences. Treatments available for patients with congenital GnRH deficiency such as Kallmann syndrome include gonadal steroid hormones, human gonadotropins and GnRH. The choice of therapy depends on the goal or goals.
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http://dx.doi.org/10.1530/EDM-17-0083DOI Listing
September 2017

Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting.

J Clin Lipidol 2018 Nov - Dec;12(6):1452-1462. Epub 2018 Sep 7.

Institut de Recerca - Hospital de la Santa Creu i Sant Pau, Serveis de Bioquímica, i d'Endocrinologia i Nutrició, IIB Sant Pau, CIBERDEM, Universitat Autònoma de Barcelona, Departaments de Bioquímica i Biologia Molecular, i Medicina, Barcelona, Spain. Electronic address:

Background: Autosomal dominant hypercholesterolemia (ADH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is estimated to be greatly underdiagnosed. The most cost-effective strategy for increasing ADH diagnosis is a cascade screening from mutation-positive probands.

Objective: The objective of this study was to evaluate the results from 2008 to 2016 of ADH genetic analysis performed in our clinical laboratory, serving most lipid units of Catalonia, a Spanish region with approximately 7.5 million inhabitants.

Methods: After the application of the Dutch Lipid Clinic Network (DLCN) clinical diagnostic score for ADH, this information and blood or saliva from 23 different lipid clinic units were investigated in our laboratory. DNA was screened for mutations in LDLR, APOB, and PCSK9, using the DNA-array LIPOchip, the next-generation sequencing SEQPRO LIPO RS platform, and multiplex ligation-dependent probe amplification (MLPA). The Simon Broome Register Group (SBRG) criteria was calculated and analyzed for comparative purposes.

Results: A total of 967 unrelated samples were analyzed. From this, 158 pathogenic variants were detected in 356 patients. The main components of the DLCN criteria associated with the presence of mutation were plasma LDL cholesterol (LDLc), age, and the presence of tendinous xanthomata. The contribution of family history to the diagnosis was lower than in other studies. DLCN and SBRG were similarly useful for predicting the presence of mutation.

Conclusion: In a real clinical practice, multicenter setting in Catalonia, the percentage of positive genetic diagnosis in patients potentially affected by ADH was 38.6%. The DLCN showed a relatively low capacity to predict mutation detection but a higher one for ruling out mutation.
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http://dx.doi.org/10.1016/j.jacl.2018.09.002DOI Listing
October 2019

Treatment with growth hormone in the prader-willi syndrome.

Endocrinol Diabetes Nutr 2018 Apr 3;65(4):229-236. Epub 2018 Mar 3.

Servicio de Endocrinología y Nutrición, Hospital Universitari Parc Tauli, , Sabadell, España. Electronic address:

Introduction: The Prader-Willi syndrome (PWS) is a rare genetic disorder caused by absence of expression of the paternal alleles in región 15q11.2-q13. Obesity and hormonal deficiencies, especially of growth hormone (GH), are the most important signs from the therapeutic viewpoint. Recombinant GH (rGH) is effective in children and represents the mainstay in treatment; by contrast, little evidence in available in adult patients.

Objective: To review the reported evidence on the beneficial and adverse effects of treatment with rGH in children and adults.

Design: A review was made of 62 original articles published between 2000 and 2017 using the PubMed database.

Results: In pediatric and adult PWS, rGH improves body morphology and composition, physical performance, cognition, psychomotor development, respiratory function, and quality of life with few adverse effects.

Conclusions: Treatment with rGH is effective and safe and improves quality of life in both children and adults with PWS.
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http://dx.doi.org/10.1016/j.endinu.2018.01.006DOI Listing
April 2018

Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy.

Diabetes Technol Ther 2018 04 22;20(4):296-302. Epub 2018 Feb 22.

3 Pathology Department, Parc Taulí Sabadell University Hospital, Institut d'Investigacio i Innovació Parc Taulí, Autonomous University of Barcelona , Barcelona, Spain .

Background: Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance.

Methods: Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%.

Results: Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm; P < 0.05).

Conclusion: The accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.
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http://dx.doi.org/10.1089/dia.2017.0321DOI Listing
April 2018

Clinical and ultrasonographic features associated to response to intraarticular corticosteroid injection. A one year follow up prospective cohort study in knee osteoarthritis patient with joint effusion.

PLoS One 2018 19;13(1):e0191342. Epub 2018 Jan 19.

Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain.

Objectives: Intraarticular injection is used for pain relief in knee osteoarthritis (OA), but there is not a well defined profile of patient who could get more benefit from it. The purpose of this study was to evaluate the frequency of pain relief at one year after corticosteroids intraarticular injection and to identify clinical factors associated to response in patients with knee osteoarthritis with joint effusion.

Methods: One-year prospective cohort study of patients with knee OA with joint effusion confirmed by ultrasound. An intraarticular injection was performed following a clinical protocol. Anthropometric measurements, laboratory parameters, clinical severity, ultrasound parameters and radiological severity were collected. Response regarding pain and presence of synovial fluid on ultrasound at one month and at one year were evaluated. Clinical responder were consider in subjects with enough improvement to carry out normal daily activities with pain VAS<40mm.

Results: One hundred and thirty-two patients were included.A significant number of patients (61.4%) improved pain at one year following the protocol established in this study. Pain and ultrasound synovial fluid at one month appeared to predict the response at one year. The Lequesne index and the percentage of body fat were independently associated to pain at one year while the Lequesne index and ultrasound synovial hypertrophy were independently related to the presence of synovial fluid at one year.

Conclusions: The status regarding pain or ultrasound synovial fluid at one month after an intraarticular joint injection appeared to predict the status at one year in patients with knee osteoarthritis and synovial effusion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191342PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774783PMC
March 2018

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial.

PLoS One 2018 10;13(1):e0190849. Epub 2018 Jan 10.

Department of Endocrinology, Bone Diseases, Genetics, and Gynaecology, Children's Hospital, Toulouse, France.

Context And Objective: Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available.

Methods And Design: Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures.

Results: AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion.

Conclusions: AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190849PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761957PMC
February 2018

Improvement in cognitive abilities following cabergoline treatment in patients with a prolactin-secreting pituitary adenoma.

Int Clin Psychopharmacol 2018 03;33(2):98-102

Departments of Mental Health, CIBERSAM.

Hyperprolactinaemia may affect sexual and reproductive functioning. However, recent studies suggest that increased prolactin levels may also have negative effects on cognition. We aimed to study whether the reduction in prolactin levels by cabergoline in patients with hyperprolactinaemia is followed by an improvement in cognitive tasks. We studied seven patients with hyperprolactinaemia caused by a prolactinoma that had an indication to start treatment with cabergoline. All patients were assessed twice (baseline and 6-12 months after cabergoline treatment) with a cognitive battery. Plasma prolactin levels were determined. We found a significant improvement in the speed of processing, working memory, visual learning and reasoning and problem-solving domains after cabergoline treatment. Improvements in speed of processing and reasoning and problem solving were greater in patients with baseline prolactin levels above the median. In summary, a reduction in prolactin levels by cabergoline in patients with hyperprolactinaemia is followed by an improvement in cognitive abilities. This finding suggests that prolactin may be involved in cognitive processes, although cabergoline could also have procognitive effects that are independent of prolactin changes. Further clinical trials are needed to confirm the potential cognitive-enhancement properties of cabergoline in patients with chronic hyperprolactinaemia.
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http://dx.doi.org/10.1097/YIC.0000000000000199DOI Listing
March 2018

Mapping the sequence of brain events in response to disgusting food.

Hum Brain Mapp 2018 01 11;39(1):369-380. Epub 2017 Oct 11.

Endocrinology and Nutrition Department, Sabadell University Hospital (UAB), Corporació Sanitària Parc Taulí, Sabadell, 08208, Spain.

Warning signals indicating that a food is potentially dangerous may evoke a response that is not limited to the feeling of disgust. We investigated the sequence of brain events in response to visual representations of disgusting food using a dynamic image analysis. Functional MRI was acquired in 30 healthy subjects while they were watching a movie showing disgusting food scenes interspersed with the scenes of appetizing food. Imaging analysis included the identification of the global brain response and the generation of frame-by-frame activation maps at the temporal resolution of 2 s. Robust activations were identified in brain structures conventionally associated with the experience of disgust, but our analysis also captured a variety of other brain elements showing distinct temporal evolutions. The earliest events included transient changes in the orbitofrontal cortex and visual areas, followed by a more durable engagement of the periaqueductal gray, a pivotal element in the mediation of responses to threat. A subsequent core phase was characterized by the activation of subcortical and cortical structures directly concerned not only with the emotional dimension of disgust (e.g., amygdala-hippocampus, insula), but also with the regulation of food intake (e.g., hypothalamus). In a later phase, neural excitement extended to broad cortical areas, the thalamus and cerebellum, and finally to the default mode network that signaled the progressive termination of the evoked response. The response to disgusting food representations is not limited to the emotional domain of disgust, and may sequentially involve a variety of broadly distributed brain networks. Hum Brain Mapp 39:369-380, 2018. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866415PMC
January 2018

Gastric Dilatation and Abdominal Compartment Syndrome in a Child with Prader-Willi Syndrome.

Am J Case Rep 2017 Jun 7;18:637-640. Epub 2017 Jun 7.

Department of Paediatric Endocrinology, Parc Tauli Sabadell, Hospital Universitari, Universitat Autònoma de Barcelona, Sabadell, Spain.

BACKGROUND Prader-Willi syndrome (PWS) is a genetic disorder characterized by initial muscular hypotonia and feeding difficulties, and later an insatiable appetite, hyperphagia and obesity along with mild to moderate intellectual impairment. Affected individuals' food-seeking behavior and suspected delayed gastric emptying can lead to gastric dilatation with subsequent necrosis and perforation. CASE REPORT We present the case of a 5-year-old boy diagnosed with Prader-Willi syndrome at neonatal age due to muscular hypotonia, who started growth hormone therapy at 20 months. He presented with two episodes of a rapidly progressing gastric dilatation that led to abdominal hypertension and secondary shock at the age of 2 and 5. No large amount of food was eaten before any of the episodes, and he had abdominal pain and vomiting on both occasions. On arrival at the emergency room, a nasogastric tube was placed and aspiration of food material was performed. Abdominal X-ray and CT scan revealed massive gastric dilatation. He was admitted at the Pediatric Intensive Care Unit and after a variable period of fasting, tolerated oral intake and could be discharged. CONCLUSIONS Gastric dilatation due to gastroparesis in PWS is a rare complication. However, it is a life-threatening situation and physicians should therefore maintain a high level of suspicion for gastric dilatation when patients present with warning symptoms such as abdominal pain or discomfort and vomiting.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469321PMC
http://dx.doi.org/10.12659/ajcr.903608DOI Listing
June 2017

Takotsubo cardiomyopathy in amiodarone-induced hyperthyroidism.

Endocrinol Diabetes Metab Case Rep 2017 15;2017. Epub 2017 Feb 15.

Endocrinology Department, Parc Taulí Sabadell University Hospital, Sabadell Barcelona, Spain.

Summary: Takotsubo cardiomyopathy (TC) is an atypical, severe but reversible form of acute heart insufficiency. It typically presents with left ventricular failure, transient apical and mid-segments hypokinesis, absence of significant coronary stenosis and new electrographic abnormalities and/or elevation in serum cardiac enzymes. Although TC ('broken heart syndrome') has classically been associated with emotional trauma, evidence suggests that other precipitants might exist, including iatrogenic and thyroid-mediated forms. Thyroid disease is a relatively common comorbidity in TC patients. We report a case of TC in a postmenopausal female with no history of emotional trauma or other potential precipitant factors who was diagnosed with amiodarone-induced hyperthyroidism during her hospital stay. Though some case reports of thyroid-related TC exist, we are not aware of any other reported case of TC precipitated by amiodarone-induced hyperthyroidism.

Learning Points: TC is a relatively new, rare, transient, severe, but reversible cardiovascular condition that is characterized by an acute left ventricular cardiac failure, which can clinically, analytically and electrocardiographically mimic an acute myocardial infarction.Many precipitant factors have been described in TC, being the most classical and emotional trauma. However, thyroid dysfunction is also a significant condition frequently found in patients with TC.A hypercatecholaminergic state leading to cardiomyocyte damage has been established as the main fact of TC physiopathology. Hyperthyroidism induces an upregulation of β-adrenergic receptors.Both hyperthyroidism and hypothyroidism have been related with TC development. Most reported cases of TC involving thyroid dysfunction correspond to hyperthyroidism due to Graves-Basedow disease, but there are also descriptions with severe hypothyroidism, radioiodine treatment or thyroid surgery.Amiodarone is a class III antiarrhythmic agent widely used, and it is a well-known cause of thyroid dysfunction, which can present either with hypothyroidism or hyperthyroidism, as approximately 40 percent of the amiodarone molecule is composed of iodine.In this case, a type II amiodarone-induced hyperthyroidism was the precipitant factor of a TC in a patient with a pre-existing atrial fibrillation. Given the high prevalence of atrial fibrillation and the wide use of amiodarone, the risk of this iatrogenic effect should be taken into account.
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http://dx.doi.org/10.1530/EDM-16-0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404472PMC
February 2017

Impact of Bariatric Surgery on Heme Oxygenase-1, Inflammation, and Insulin Resistance in Morbid Obesity with Obstructive Sleep Apnea.

Obes Surg 2017 09;27(9):2338-2346

Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Universitat Autònoma de Barcelona, c/ Parc Taulí no 1, 08208, Sabadell, Barcelona, Spain.

Introduction: Morbid obesity and obstructive sleep apnea (OSA) interact at an inflammatory level. Bariatric surgery reduces inflammatory responses associated with obesity. Heme oxygenase-1 (HO-1) is an enzyme with anti-inflammatory properties, which might be increased in morbid obesity or OSA. We studied morbidly obese patients with OSA to determine: (a) HO-1 plasma concentrations according to OSA severity and their relationship with insulin resistance and inflammation and (b) the impact of bariatric surgery on HO-1 and parameters of insulin resistance and inflammation.

Material And Methods: We analyzed the homeostasis model insulin resistance index (HOMA) and plasma concentrations of HO-1, tumor necrosis factor alpha, interleukin-6, interleukin-1-beta, C reactive protein (CRP), and adiponectin according to polysomnography findings in 66 morbidly obese patients before bariatric surgery and 12 months after surgery.

Results: Before surgery, HO-1 plasma concentrations were similar in three groups of patients with mild, moderate, and severe OSA, and correlated with HOMA (r = 0.27, p = 0.02). Twelve months after surgery, low-grade inflammation and insulin resistance had decreased in all the groups, but HO-1 plasma concentration had decreased only in the severe OSA group (p = 0.02). In this group, the reduction in HO-1 correlated with a reduction in CRP concentrations (r = 0.43, p = 0.04) and with improved HOMA score (r = 0.37, p = 0.03).

Conclusions: Bariatric surgery decreases HO-1 concentrations in morbid obesity with severe OSA, and this decrease is associated with decreases in insulin resistance and in inflammation.
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http://dx.doi.org/10.1007/s11695-017-2635-4DOI Listing
September 2017

Long-Term Outcomes in Patients with Morbid Obesity and Type 1 Diabetes Undergoing Bariatric Surgery.

Obes Surg 2017 04;27(4):856-863

Endocrinology and Nutrition Department, Hospital Universitari Arnau de Vilanova, Avda. Rovira Roure 80, 25198, Lleida, Spain.

Background: This study aims to describe the long-term outcomes of bariatric surgery in a cohort of patients with type 1 diabetes (T1DM).

Methods: Thirty-two patients with T1DM and initial BMI of 41.3 ± 4.8 kg/m were studied, 18.7 % undergoing duodenal switch (DS), 34.4 % gastric bypass, and 46.9 % sleeve gastrectomy and followed-up after surgery for 4.6 ± 2.6 years. Changes in BMI, HbA, insulin requirements, evolution of comorbidities, and microvascular complications were registered annually after surgery.

Results: Percentage of total weight loss (%TWL) 12 months after surgery was 30.4 ± 9.2 % and at 5 years, it decreased to 28.1 ± 11.5 % (p = 0.02). HbA was reduced during the first year from 8.5 ± 1.3 to 7.9 ± 1.4 %, p = 0.016. In the long-term, HbA returned to baseline values. There was a sustained reduction of 51 % in total daily insulin dose, and the decrease in the number of patients with hypertension, dyslipidemia, and obstructive sleep apnea was 42.8, 25, and 66 %, respectively. Retinopathy remained mainly unaffected, and 25 % of patients with microalbuminuria regressed to normoalbuminuria.

Conclusions: Bariatric surgery in patients with T1DM mainly provides benefits of weight reduction, on insulin requirements, obesity comorbidities, and some benefits in diabetes complications, but might have only minimal effect on the glycemic control in the long term. This trial was registered at www.controlledtrials.com as ISRCTN49980913.
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http://dx.doi.org/10.1007/s11695-016-2390-yDOI Listing
April 2017

Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome.

PLoS One 2016;11(9):e0163468. Epub 2016 Sep 29.

Department of Endocrinology and Nutrition, Sabadell University Hospital, Corporació Sanitària Parc Taulí, Sabadell, Spain, Autonomous University of Barcelona, Bellaterra, Spain.

Context: Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis.

Objectives: To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS.

Design: Experimental study.

Setting: University hospital.

Subjects: 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls.

Interventions: Subjects ingested a liquid meal after fasting ≥10 hours.

Main Outcome Measures: Leptin and BDNF levels in plasma extracted before ingestion and 30', 60', and 120' after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60' and 120' after ingestion.

Results: Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05). Leptin was higher in PWS patients than in controls at all time points (p<0.001). PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65-0.94). In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13-0.9). Postprandial leptin patterns did no differ among genetic subtypes.

Conclusions: Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163468PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042477PMC
September 2016