Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?

BACKGROUND: Fibroblast growth factor 21 (FGF21) has been suggested to be an endocrine signal of nutritional status and an active regulator of metabolism. However, there is no agreement on the effect of weight-loss therapies on circulating levels of FGF21 in humans. OBJECTIVE: To assess FGF21 circulating levels in adiposity excess and after different weight-loss strategies prescribed in five different groups from four independent centers. SUBJECTS AND METHODS: Body composition, ketosis, insulin sensitivity and FGF21 were evaluated in 181 excess body weight and 14 normal-weight subjects. From the excess body weight patients, two independent groups (discovery cohort; n=20 and validation cohort; n=28) undertook a very low-calorie ketogenic (VLCK) diet, a third group followed a low-calorie (LC) diet (n=84) and other two groups underwent bariatric surgery (discovery cohort; n=24 and validation cohort; n=25). The follow-up was 4 to 6 or 12 months, respectively. RESULTS: FGF21 levels were higher in excess body weight patients than in normal-weight subjects. The energy-restriction therapy to lose weight induced a significant decrease, with respect to baseline, in circulating levels of FGF21 (VLCK: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obese patients showed a significant increase in FGF21, especially 1 month after surgery (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: FGF21 levels were reduced after energy-restricted treatments and severely increased after bariatric surgery, independently of the weight reduction magnitude, insulin sensitivity or ketosis. Therefore, FGF21 appears to be a marker of severe nutritional stress.

Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes.

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.

Lymphangioleiomyomatosis: a study of 72 patients from the Spanish registry.

BACKGROUND: Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease that almost exclusively affects young women of childbearing age. The true incidence and prevalence of LAM are unknown. This study was conducted to evaluate the characteristics of lymphangioleiomyomatosis in Spain. METHODS: Over a 2-year period, a questionnaire designed for this study was collected. This questionnaire included sociodemograhic, clinical, radiological and functional data. Information about the study and this questionnaire were both sent by e-mail to all the participants of the interstitial disease registry of 2004. RESULTS: Seventy-two patients, all of whom were women, were included in the registry, with a mean age of 44.56 +/- 11.1 yr. Sixty-three patients (87.5%) presented the sporadic LAM and 9 (12.5%) presented LAM associated with tuberous sclerosis (LAM-TS). LAM diagnosis was confirmed with an open lung biopsy in 57 patients (79.2%) and was performed with thoracic HRCT compatible with LAM diagnosis in the other 15 cases. The most frequent symptom was dyspnoea (90%) followed by cough (44.4%). Almost 40% of patients presented renal angiomyolipomas in the study and the most frequent spirometric pattern was obstructive in more than half of the patients. Most patients with LAM-TS (88.8%) had renal angiomyolipomas compared with 31.7% in the sporadic LAM group. CONCLUSION: The characteristics of the Spanish population affected with LAM are similar to those of other countries. Most patients were symptomatic, had a history of previous pneumothorax and presented abnormal radiological findings and pulmonary function tests.

Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism.

The assessment of risk and appropriate treatment of patients with acute pulmonary embolism (PE) remains a challenge. The prognostic performance of cardiac troponin I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in consecutive haemodynamically stable patients with PE. The present study included 318 haemodynamically stable patients with PE. During the 30-day study period, 23 (7%) patients died. cTnI was elevated (>or=0.1 ng x mL(-1)) in 102 (32%) patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of illness assessed using the PE severity index (PESI) were significantly associated with an increased risk for mortality, but no significant association was found between elevation of cTnI and 30-day mortality in a logistic regression analysis. When only fatal PE was considered, multivariate analysis showed that severity of illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence interval (CI) 1.1-12.8) were associated with a significant increase in the risk for death. The negative predictive value (95% CI) of a negative cTnI for mortality was 93 (90-97)%. In conclusion, in haemodynamically stable patients with acute pulmonary embolism, cardiac troponin I was not an independent predictor of 30-day all-cause mortality, although it did predict fatal pulmonary embolism.

Burden assessment in caregivers of patients with home artificial nutrition: a need and a challenge.

BACKGROUND/OBJECTIVES: Caregiving can be a stressful task with severe consequences on caregivers' health. Our aim was to evaluate the profile and the burden of caregivers of patients with home artificial nutrition (HAN) in our area. SUBJECTS/METHODS: We conducted a prospective observational study of patients who had started HAN over a period of a year (n=573) and their home caregivers (n=103). Epidemiological characteristics of the patients and the type of HAN were registered. Caregivers' profile data (gender, age and degree of kinship) and Zarit Burden Assessments were recorded. RESULTS: Care recipients had a median age of 79.0 (IQR 87) years, neurological and oncological diseases in 50% and a high rate of mobility limitations (80%). Oral supplements with high-calorie formulas were predominant (60%). The usual caregiver profile was a patient's daughter with a mean age of 53.1 (s.d. 13.4) years acting as the primary caregiver. Burden was absent in 49.5%, light in 18.4% and intense in 32% of caregivers. Intense burden was more frequent in oral over enteral nutrition (42% versus 22.6%; P=0.036). Supplementary nutrition was also associated with higher caregiver burden scores compared with complete diets. In patients with functional limitations, a tendency toward a slightly higher burden was observed. No differences in caregiver burden were detected according to other patient or caregiver characteristics. CONCLUSIONS: HAN type appears to be a factor influencing caregiver burden and therefore, evaluation of caregiver burden should be part of HAN programs.

Routine use of pleural fluid cultures. Are they indicated? Limited yield, minimal impact on treatment decisions.

In pleural infection, it has been recommended that Gram stain and cultures should be obtained on a routine basis. However, this recommendation has not been tested prospectively. We evaluated the yield of microbiological studies in 259 patients with parapneumonic pleural effusion. Microbiological studies were positive on the pleural fluid of 50 patients (19.3%). In 48 of the 50 patients with positive microbiological results (96%), the need for pleural drainage was correctly predicted by pleural fluid parameters. There were no differences in hospital stay (9.5+/-2.5 days versus 9.9+/-3.2 days, P=0.68) or in mortality (2 deaths in each group, P=0.58) between the group of patients in which antibiotic treatment was changed according to microbiological results and the group of patients in which it is not. In conclusion, this study demonstrates that, at least in our institution, routine microbial investigation of pleural fluid adds very little to the standard management of parapneumonic effusions.

Introduction of Basic Dermatologic Ultrasound in Undergraduate Medical Education.

Purpose: Teaching ultrasound procedures to undergraduates has recently been proposed to improve the quality of medical education. We address the impact of applying standardized dermatologic ultrasound teaching to our undergraduates. Materials and Methods: Medical students were offered an additional theoretical and practical seminar involving hands-on ultrasound dermatologic ultrasound during their mandatory dermatology practical training. The students' theoretical knowledge and dermatologic ultrasoud skills were tested with a multiple choice questionnaire extracted from Level 1 Spanish Society of Ultrasound Dermatologic Ultrasound accreditation exam before and after the course. After the course, the students were asked to answer a course evaluation questionnaire Results: The multiple-choice question scores after the course showed statistically significant improvement (5.82 vs. 8.71%; P<0.001). The questionnaire revealed that students were satisfied with the course, felt that it increased both their dermatologic and ultrasound knowledge, and indicated that they wanted more sonographic hands-on training in both dermatologic ultrasound and other medical fields. Conclusion: Using both objective and subjective methods, we showed that the introduction of standardized ultrasound training programs in undergraduate medical education can improve both students' understanding of the technique and the quality of medical education in dermatology.

[Prognostic value of syncope in the presentation of pulmonary embolism]. / El síncope como forma de presentación de la embolia de pulmón: valor pronóstico.

OBJECTIVE: Although the prognostic value of syncope has not been specifically addressed, it has generally been considered an indicator of poor prognosis in pulmonary embolism. The objective of this study was to carry out a prospective evaluation of the risk of recurrence and/or death in patients with pulmonary embolism that presents with syncope. PATIENTS AND METHODS: A total of 168 patients had a confirmed diagnosis of pulmonary embolism. Twelve were lost to follow up and did not enter statistical analysis. The mean follow-up period was 5 months. RESULTS: The prevalence of syncope in the patients studied was 22%. Of the 34 patients who presented syncope, objectively confirmed recurrence occurred in 2 (5.9%). In the patients who did not present syncope, recurrence was confirmed in 8 (6.6%; P=.8). Death occurred in 2 patients (5.9%) from the group presenting syncope and 15 (12.3%) from the remaining patients in the series (P=.4). The relative risk of recurrence and/or death associated with presentation of syncope was 0.5 (95% confidence interval, 0.2-1.8). A similar risk was obtained following adjustment for the presence or absence of cancer or deep vein thrombosis. CONCLUSIONS: Patients with pulmonary embolism that presents with syncope do not have an increased risk of recurrence and/or death.

Long-term clinical follow-up of adult idiopathic pulmonary hemosiderosis and celiac disease.

A 22-year-old man with a history of repeated whole blood transfusions since the age of 7, was admitted to the hospital for dyspnea and blood-stained sputum. A complete blood cell count, a test for reticulin antibodies, an x-ray film of the chest, a transbronchial biopsy and a biopsy of the small bowel were performed and the results confirmed the diagnosis of IPH, associated with CD. The patient has been asymptomatic for four years on a gluten-free diet. In cases of IPH, it may be important to investigate the coexistence of CD because treatment of the latter could lead to a better prognosis.

Toxic-oil syndrome. Gallium-67 scanning and bronchoalveolar lavage studies in patients with abnormal lung function.

The toxic-oil syndrome (TOS) is a multisystem disorder whose etiology and pathogenesis are as yet unknown. Lung alterations persist in a significant number of TOS patients due to the underlying vascular lesion. Computer-assisted 67Ga scanning and bronchoalveolar lavage (BAL) studies were performed in 14 TOS patients with sustained abnormal diffusing capacity for carbon monoxide (Dco). No significant difference was observed between the 67Ga uptake index of the TOS and control populations. Likewise, there was no significant difference in the number of effector cells recovered from the lungs of TOS patients and controls by bronchoalveolar lavage. However, a rise in IgA and IgG concentrations (p less than 0.002) and a fall in alpha 1-antitrypsin (p less than 0.05) and transferrin (p less than 0.01) were observed in the TOS group. Phospholipid and lecithin concentrations in the lavage fluid were similar for patients and controls. The alveolar macrophage function assayed in three TOS patients was normal. These observations raise new questions about the outcome of lung pathology in TOS and warrant further follow-up studies of the lung abnormalities observed.

Toxicodermia secundaria a sobredosificación de omeprazol de curso atípico / Skin toxicity secondary to an overdose of omeprazole: An atypical course

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