Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cells.

BACKGROUND & AIMS: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. METHODS: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. RESULTS: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. CONCLUSIONS: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes.

Evaluation of Vitamin and Trace Element Requirements after Sleeve Gastrectomy at Long Term.

BACKGROUND: Nutritional deficiencies are common after bariatric surgery, but data are scarce after sleeve gastrectomy (SG) at long term. METHODS: We performed a prospective nutritional status evaluation before and at 2 and 5 years after SG in morbid obese patients receiving mulvitamin and mineral supplementation at a Spanish university hospital. One hundred seventy-six patients (49.3 ± 9.1 years and 46.7 ± 7.4 kg/m2) were evaluated; 51 of them were followed during 5 years. Anthropometric, compliance supplementation intake, and micronutrient evaluation were performed. RESULTS: Baseline concentrations were below normal values for 25(OH) vitamin D (73%), folic acid (16.5%), cobalamin (6.9%), pyridoxine (12%), thiamine (3.4%), and copper (0.5%). Anemia was found in 23%. In 49% of the subjects, at least one micronutrient deficiency was found at 2 years after SG. Vitamin D deficiency persisted at 2 and 5 years higher than 30% of patients. Frequencies of deficiencies for folic acid, B12, B6, and B1 vitamins decreased significantly after 2 years with normalization at 5 years. Copper deficiency increased between 1 and 2 years and it persisted at 5 years after SG. Vitamin supplementation compliance decreased progressively from the first year after surgery (94.8 to 81% at 2 years and to 53% 5 years after surgery). CONCLUSIONS: Vitamin D deficiency is the most prevalent long-term nutritional deficiency after SG. About half of patients show some micronutrient deficiency at medium long term, despite supplementation. A proactive follow-up is required to ensure a personalized and adequate supplementation in all surgically treated obese patients including those in which SG has been performed.

IGF1 modifications after bariatric surgery in morbidly obese patients: potential implications of nutritional status according to specific surgical technique.

OBJECTIVES: IGF1 is decreased in morbidly obese (MO) patients and its changes after bariatric surgery weight loss (WL) are not well known. The aim of this study was to analyse IGF1 modifications in MO patients after WL and its relationship to ghrelin and to different types of surgeries. DESIGN: Retrospective follow-up study at the University Medical Center. METHODS: One hundred and nine MO patients (age 44.19.3, BMI 51.748.75KG/M(2)) were evaluated at baseline and 1 year after surgery: 28 sleeve gastrectomy (SG), 31 distal modified (m), and 50 ringed (r) Roux-en-Y gastric bypass (RYGBP) surgery. Changes in IGF1, IGFBP3, ratio IGF1:IGFBP3, and ghrelin were evaluated 1 year after surgery. RESULTS: Baseline prevalence of low IGF1 (defined by s.d. IGF1<-2) was 22%, and %WL 1 year after surgery was 34.9±8.9%. There was a significant decrease in IGFBP3 in all the procedures, an increase in IGF1:IGFBP3 ratio in rRYGBP and SG, but total IGF1 only increased significantly in SG. Albumin concentrations decreased in mRYGBP, did not change in rRYGBP, but increased in SG after surgery. Total ghrelin concentrations increased after both RYGBPs and decreased after SG (P<0.05 in all cases). The prevalence of low IGF1 decreased in SG (28.6 vs 10.1%, P=0.03) and did not change in RYGPBP techniques. The %albumin change was the only dependent variable associated with the % total IGF1 change. CONCLUSIONS: Recovery of low IGF1 after bariatric surgery was specifically related to the albumin modifications induced by surgery and was not related to ghrelin modifications.

Intact parathyroid hormone measurement at 24 hours after thyroid surgery as predictor of parathyroid function at long term.

BACKGROUND: There is no consensus about the usefulness of postoperative intact parathyroid hormone (iPTH) determination to predict permanent hypoparathyroidism (pHPP). We evaluated the value of calcium (Ca2+) and iPTH concentration at 24 hours after total thyroidectomy (TT) for predicting pHPP. METHODS: Ca2+ and iPTH levels from 70 consecutive patients who underwent TT were measured at 24 hours and 6 months after TT. RESULTS: Five patients (7.1%) developed pHPP. An iPTH concentration ≤5.8 pg/mL at 24 hours after TT identified patients at risk for pHPP (sensitivity, 100%; specificity, 81.5%), but it was not accurate enough to predict its development (positive predictive value, 30%). Conversely, an iPTH level >5.8 pg/mL predicted normal parathyroid function at 6 months (negative predictive value, 100%). Compared with iPTH, a postoperative Ca2+ level ≤1.95 mmol/L was 60% sensitive and 78.5% specific to predict pHPP. CONCLUSIONS: An iPTH concentration >5.8 pg/mL on the first postoperative day rules out pHPP with much better diagnostic accuracy than Ca2+. Postoperative iPTH could be helpful in identifying patients at risk for developing pHPP.

Leptin and thyrotropin relationship is modulated by smoking status in euthyroid subjects.

BACKGROUND: The relationship between thyrotropin (TSH) concentrations and body mass index (BMI) in euthyroid subjects has been demonstrated only in some studies. Leptin regulates TSH secretion and TSH stimulates leptin secretion. The main aims of our study were to assess the relationship between leptin, the thyroid axis, and thyroid autoimmunity in a representative sample of a nonhospitalized euthyroid adult population of Catalonia and to determine whether smoking status could influence this relationship. METHODS: This cross-sectional population-based study includes 894 euthyroid iodine-sufficient adults (390 men, 44.87±15.03 years old) with BMI 26.19±4.61 kg/m(2), representative of people living in Catalonia. The study analyzes the relationship between TSH, free thyroxine (FT4), leptin, thyroperoxidase and/or thyroglobulin antibodies (thyroid autoimmunity), smoking status, and BMI. Measurements also include glycemia and insulinemia to calculate homeostasis model assessment of insulin resistance (HOMA-IR) index as a measure of insulin sensitivity. RESULTS: In the univariate analysis and in the overall group, TSH correlated directly with BMI, leptin, and HOMA-IR (p=0.039, p<0.001, and p=0.010, respectively). In all men, TSH correlated directly with leptin (p=0.004), and in all women, directly with leptin (p=0.002) and HOMA-IR (p=0.031) and inversely with FT4 (p=0.024). Only in men who smoke, TSH correlated directly with leptin (p=0.010) and HOMA-IR (p=0.024). In women, TSH correlated directly with leptin (p=0.004) and in nonsmoking women, inversely with FT4 (p=0.047). In the multiple regression analysis, age (ß=-0.00310, p=0.0265), smoking status (ß=-0.24085, p=0.0202), and thyroid autoimmunity (ß=0.20652, p=0.0075) were independent predictors of TSH variations. Leptin was a significant independent predictor of TSH variations only in smokers (ß=0.16451, p=0.047). CONCLUSIONS: Leptin is an independent predictor of TSH concentration variations only in euthyroid smoker subjects of both sexes at all ranges of BMI, but not in nonsmokers. Age, smoking status, and positive thyroid autoimmunity also influenced TSH variability.

Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery.

BACKGROUND: The effect of weight loss by bariatric surgery on gonadal hormones in morbidly obese males is not entirely known. The main objective of the study was to analyze gonadal hormonal changes after weight loss. METHODS: An observational study was conducted before and after 12 months of weight loss at a clinical research center. Thirty-three men [age 40.5 ± 9.9, body mass index (BMI) 50.3 ± 6.1 kg/m(2)] undergoing bariatric surgery were included. The main outcome measures were as follows: changes in total (TT) and free testosterone (FT), estradiol (E2), sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), inhibin B, and prolactin (PRL). RESULTS: Baseline prevalence of hypogonadism (defined by TT < 300 ng/dl or FT < 65 pg/ml) was 78.8 and 51.5%, respectively. Hypogonadal patients were older and showed inhibin B and AMH significantly lower than those with normal TT. BMI correlated negatively with TT, LH, and SHBG. Regression analyses showed a significant and independent association of hypogonadism with age (OR = 1.2, p = 0.01), BMI (OR = 1.3, p = 0.03), and AMH (OR = 0.4, p = 0.03) after adjustments. After 1 year, percentage of weight loss (%WL) was 18.8 ± 5.2%, and there was a significant increase of TT, FT, SHBG, and FSH and a decrease of E2 and PRL. Prevalence of persistent hypogonadism after surgery was 6% (low TT) and 15% (low FT). %WL was significantly associated with percent changes in SHBG (r = -0.4, p = 0.04), inhibin B (r = -0.4, p = 0.03), and AMH (r = -0.4, p = 0.01). Age and %WL were the only significant and independent parameters associated with %TT change. CONCLUSIONS: Obesity-associated hypogonadism is very prevalent in males with morbid obesity and is mostly reversed after sustained weight loss by bariatric surgery.

Effects of two variants of Roux-en-Y Gastric bypass on metabolism behaviour: focus on plasma ghrelin concentrations over a 2-year follow-up.

BACKGROUND: To study the effects of two variants of Roux-en-Y gastric bypass (RYGBP) on plasma ghrelin concentrations according to different exposure of gastric fundus to the nutrient pathway. METHODS: A prospective longitudinal 2-year follow-up study was conducted. Ninety-six morbidly obese (MO) patients (age range: 41.6 +/- 9.6 years, body mass index: 53 +/- 9.5 kg/m(2)) were assigned to two bariatric surgical (BS) procedures: one that preserves food contact with gastric fundus (ringed RYGBP, n = 50) and the other that avoids it (modified RYGBP, n = 46). Different anthropometric and biochemical parameters were studied, focusing on ghrelin concentrations at baseline and 6, 12, and 24 months post-BS. RESULTS: At 24 months post-BS, all metabolic parameters studied had improved in all patients compared with those at 1-year follow-up and baseline (p < 0.05). However, high-density lipoprotein cholesterol concentrations took 2 years to normalise in 80% of patients, interleukin-6 decreased significantly in relation to baseline only after 2 years from BS (p < 0.001), and tumour necrosis factor alpha concentrations did not significantly decrease during the 2 years of follow-up. Plasma ghrelin concentrations increased in both surgical groups compare to baseline during the first year (24.6% in modified RYGBP and 36.62% in ringed RYGBP) and remained stable at the second year of follow-up, with no statistical differences between groups. CONCLUSIONS: In the second year of follow-up after BS, morbidity continued to improve in MO patients despite a lesser weight loss in relation to the first year. An increase in plasma ghrelin concentrations was found, regardless of nutrient contact with gastric fundus. Furthermore, changes in plasma ghrelin concentrations appeared to be independent of weight loss.

Association of the IGF1/pregnancy-associated plasma protein-A system and adipocytokine levels with the presence and the morphology of carotid plaques in type 2 diabetes mellitus patients with stable glycaemic control.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) has been implicated in the atherosclerotic process through regulation of local expression of IGF1. In type 2 diabetes mellitus, glycaemic control has been involved in PAPP-A expression. We compared PAPP-A, IGF1, inflammatory markers and adiponectin concentrations in type 2 diabetic patients with and without carotid plaques and evaluated the relationship between these serum parameters and ultrasound carotid markers of atherosclerosis. METHODS: We studied 125 consecutive type 2 diabetic patients. Clinical data, metabolic variables, hemostatic factors (plasma type-1 plasminogen activator inhibitor, fibrinogen), high-ultrasensitive C reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin, IGF1 and PAPP-A were determined. Patients were classified into two groups according to the presence of carotid plaques on ultrasound. Carotid intima-media thickness (IMT) and morphology of carotid plaques were evaluated. RESULTS: The mean age was 61.5+/-7.3 years and the mean glycated hemoglobin of 6.8+/-0.9%. A total of 60% presented carotid plaques. Both groups were homogeneous in anthropometric data, biochemical determinations and hemostatic factors. Adiponectin, hsCRP, TNF-alpha and IL-6 were similar in both groups. No differences were observed in serum PAPP-A (0.46 (0.22-0.86) vs 0.38 (0.18-0.66) mIU/l and in SDS IGF1 (-0.34+/-1.38 vs -0.67+/-1.35)) in patients with and without carotid plaques respectively. PAPP-A and IGF1 were not correlated with IMT. CONCLUSIONS: Serum PAPP-A and IGF1 do not appear to be useful serum biomarkers for carotid atherosclerosis in type 2 diabetic patients with stable glycemic control, despite scientific evidence of their local role in atherosclerosis.

Plasma ghrelin concentrations in type 1 diabetic patients with autoimmune atrophic gastritis.

OBJECTIVE: Type 1 diabetes mellitus patients (DM1) show increased prevalence of pernicious anaemia, the histological substrate of which is type A chronic atrophic gastritis (CAG) in the stomach corpus, the main source of ghrelin. We aimed to compare plasma ghrelin concentrations in DM1 patients with type A CAG (DM1-CAG), DM1 patients without type A CAG and healthy controls and in DM1-CAG group, to ascertain a possible relationship between ghrelin and biochemical markers of gastric mucosa atrophy and/or neuroendocrine (NE) cell hyperplasia and histological gastric biopsy findings. DESIGN AND METHODS: Fifteen DM1-CAG patients were matched for age, sex and body mass index with 15 DM1 patients without type A CAG and 15 controls. Pepsinogen I, pepsinogen II, gastrin, parietal cell antibodies, chromogranin A (CgA) and ghrelin were determined in all subjects. In DM1-CAG patients, immunohistochemical analysis of gastric biopsies using antibodies to CgA and ghrelin was performed. RESULTS: Ghrelin concentrations differed among groups; however, paired comparisons between groups were not significant. In DM1-CAG, no correlation was found between ghrelin and gastric body atrophy markers, pepsinogen I and the pepsinogen I/II ratio. Immunohistochemical studies of DMI-CAG patients showed CgA staining in 12 and ghrelin staining in 6, which was confined to the foci of NE cell hyperplasia. Those patients who stained positive for ghrelin had higher ghrelin concentrations when compared with the negative patients. CONCLUSIONS: Ghrelin concentrations are not decreased in DM1-CAG patients; thus, our data suggest that ghrelin is not a good marker of gastric mucosa atrophy in these patients, given the possible ghrelin synthesis in hyperplastic gastric endocrine/enterochromaffin-like cells.

Postpartum thyroiditis: long-term follow-up.

OBJECTIVE: To determine the incidence of persistent hypothyroidism (PH) after a long follow-up in 45 patients with postpartum thyroiditis (PPT) from a nonselected population of 641 pregnant women (PPT incidence 7.8%) and the clinical and biochemical factors associated with PPT evolution. DESIGN AND PATIENTS: The 45 women who developed PPT were followed for 8.1 +/- 2.2 years after delivery. MEASUREMENTS: Age at delivery, family and personal history, smoking, newborn gender, breast-feeding, and PPT course were recorded. Thyrotropin (TSH) and free thyroxine (T(4)) concentrations and antithyroid antibodies were evaluated at each visit. PH was considered when it persisted one year after being diagnosed. RESULTS: Fourteen of 45 patients with PPT developed PH with a probability of 56% after a PPT episode with hypothyroidism. None of the patients who developed hyperthyroidism alone during PPT evolved to PH. PH risk was higher if the newborn was a girl (relative risk [RR] 3.88) and increased for each additional TSH unit during PPT and for every additional year of the mother's age. CONCLUSIONS: The probability of developing PH after a PPT with hypothyroidism episode is 56%. PPT screening in all women permits us to establish levothyroxine treatment, if necessary, before a new pregnancy.

Reanimación cardiopulmonar mediante la tos: Aplicación en la práctica anestésica. Presentación de un caso / Cardiopulmonary resuscitation through cough. Implementation in the anesthetic practice. A case report

Introducción: La reanimación cardiopulmonar mediante la tos (tos-RCP), es una técnica de auto-reanimación. Se ha observado que algunos pacientes con paro cardiaco monitorizado en fibrilación ventricular, si se les ordena toser vigorosamente antes de perder la conciencia, son capaces de permanecer conscientes durante 100 segundos. Objetivo: Presentar un caso donde se aplicó la tos-RCP y argumentar su uso en la práctica anestésica. Material y método: Se presenta un paciente al cual se le aplicó con éxito la tos-RCP durante la anestesia espinal, en el H.C.Q.D. "Joaquín Albarrán", recogiéndose los datos de la historia clínica y del protocolo de anestesia archivados en el hospital. Además, se realizó una revisión bibliográfica actualizada sobre el tema. Presentación del caso: Paciente masculino, de estado físico ASA II, con el diagnóstico de hernia inguinal izquierda, para lo cual se realiza herniorrafia bajo los efectos de la anestesia espinal. A los 25 minutos de realizada la espinal, hace bradicardia aguda severa y asistolia. Inmediatamente se ordena al paciente toser vigorosamente, mientras se tomaron otras medidas para tratar la bradiasistolia; a los 45 segundos de asistolia, se restablece el ritmo sinusal, y en todo momento el paciente estuvo consciente. Conclusiones: La aplicación de la tos-RCP durante el paro vagal monitorizado en el curso de la anestesia espinal, es un método eficaz para mantener la conciencia, mientras se toman otras medidas para corregir la etiología del paro