Estudio de envejecimiento de Mataró: Factores hormonales y genéticos que influyen en el envejecimiento

[spa] Antecedentes del tema: El envejecimiento es un proceso heterogéneo caracterizado por el deterioro de la capacidad funcional y la mayor susceptibilidad a desarrollar síndrome metabólico (SM) y otras enfermedades que puede llevar a una situación de fragilidad o a una senectud robusta. Hipótesis: Determinada condición hormonal y la combinación de ciertas variantes alélicas del gen de ghrelina, IGF-I y del receptor de glucocorticoides (R-GC), se asocian a mayor prevalencia de SM y menor capacidad funcional en ancianos. Objetivos: 1) Determinar el posible papel de los ejes somatotropo, gonadal y adrenal en la capacidad funcional y el desarrollo de fragilidad en nuestra población de estudio. 2) Determinar la frecuencia de los 6 polimorfismos más frecuentes para el gen de ghrelina, la variante alélica de 192 pb del promotor del gen de IGF-I y del polimorfismo ER22/23EK del gen del R-GC. 3) Evaluar la potencial asociación entre las mencionadas variantes alélicas y la fuerza muscular, capacidad funcional, estado mental y nutricional, y la presencia de los distintos componentes del SM. 4) Estudiar el papel de la obestatina en el estado nutricional, hambre, riesgo de SM y deterioro funcional en la muestra poblacional. 5) Determinar si alguno de los marcadores metabólicos y hormonales se asocia a una mayor supervivencia en el estudio longitudinal. Metodología: estudio longitudinal observacional, de base poblacional iniciado en 2001, con los sujetos participantes en el Estudio de Envejecimiento de Mataró (EEM) y con seguimiento a 3 y 10 años (2004-2005 y 2011-2012). En dichas fases se incluyeron 310 sujetos (160M/150H) de 70a no institucionalizados. Se recogieron datos sobre criterios de SM, capacidad funcional mediante Barthel, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment (MNA), criterios de fragilidad por Fried y variables antropométicas en cada corte. Se determinaron hormonas sexuales, adrenales, IGF-I, ghrelina y obestatina totales y marcadores genéticos. Resultados y conclusiones: 1) Los ejes somatotropo, gonadal y adrenal juegan un papel en el estado de salud, el envejecimiento y el desarrollo de fragilidad, especialmente el eje adrenal en las mujeres y los ejes somatotropo y gonadal en los varones. a. El estradiol en relación al MNA, la testosterona con el índice Barthel y el MMSE, y la DHEA en relación al MMSE. b. El desarrollo de fragilidad se asocia con niveles inferiores de testosterona, pero sólo en varones. 2) La prevalencia de los distintos polimorfismos es parecido al descrito en otras poblaciones, salvo en el caso del polimorfismo ER22/23EK del gen del R-GC, que es algo inferior en nuestra muestra. 3) Existe una asociación entre las distintas variantes alélicas de los distintos genes estudiados y los componentes del SM, así como con la capacidad funcional: a. Los homocigotos para el 192 pb del promotor del gen de IGF-I tienen una mejor condición de envejecimiento, con menor prevalencia en alteraciones metabólicas y un mejor estado mental, nutricional y funcional. b. Los portadores de ER22/23EK presentan una menor prevalencia de HTA. c. Los polimorfismos de la ghrelina, especialmente -604GA, -501AC y M72L, se asocian con ciertos componentes del SM, especialmente con la obesidad central, el IMC y el perfil lipídico. d. El polimorfismo L90G se asocia a la función cognitiva. 4) La obestatina está elevada en las mujeres ancianas con el SM y: a. Parece estar asociada a cambios en el perímetro de cintura, lo que apunta a un papel de la obestatina en la obesidad. b. Se asocia a menor fuerza muscular, peor capacidad funcional y estado cognitivo. 5) En relación a la supervivencia: a. El perímetro de cintura se asocia con la supervivencia en forma de U. b. Los factores hormonales (esteroides adrenales y eje somatotropo) influyen en la supervivencia en los participantes en el EEM.[eng] Hypothesis: Certain hormonal condition and the combination of certain allelic variants of the ghrelin gene, IGF-I and glucocorticoid receptor (R-GC), are associated with higher prevalence of MS and less functional capacity in the elderly. Goals: 1) To determine the possible role of the somatotropic, gonadal and adrenal axes in functional capacity and the development of frailty in our study population. 2) To determine the frequency of the 6 most ghrelin gene polymorphisms, IGF-I gene promoter polymorphism 192bp and ER22 /23EK gene polymorphism in R-GC. 3) To evaluate the potential association between allelic variants and muscle strength, functional capacity, mental and nutritional status, and the presence of the various components of MS. 4) To study the role of obestatin in nutritional status, hunger, SM risk and functional impairment in the population sample. 5) To determine if any of the metabolic and hormonal markers is associated with a higher survival rate in the longitudinal study. Methodology: a population-based started in 2001 in which participated 310 non-institutionalized subjects (160W / 150M) of 70y from Mataro Aging Study (MAS) with a follow-up at 3 and 10 years. MS criteria data, functional capacity, hormones and genetic markers were determined. Results and conclusions: 1) The somatotropic, gonadal and adrenal axes play a role in health, aging and the development of frailty, especially the adrenal axis in women and somatotropic and gonadal axis in men. The development of frailty is associated with lower levels of testosterone in males. 2) The prevalence of different polymorphisms is similar to that described in other populations, except in the case of the ER22 / 23EK gene polymorphism in R-GC, which is somewhat lower in our sample. 3) There is an association between different allelic variants of different genes studied and MS components as well as functional capacity: a. Homozygous for the 192 by have a better condition of aging. b. The carriers of ER22 / 23EK had a lower prevalence of hypertension. c. The polymorphisms of ghrelin, especially -604GA, -501AC and M72L are associated with certain components of MS. L9OG is associated with cognitive function. 4) The obestatin is higher in elderly women with MS and it seems to be associated with changes in waist circumference and with reduced muscle strength, poor functional capacity and cognitive status. 5) Waist circumference is associated with survival in a U shape pattern. Hormonal factors (adrenal steroids and somatotropic axis) influence survival in participants in the MAS

Ketoconazole- and Metyrapone-Induced Reductions on Urinary Steroid Metabolites Alter the Urinary Free Cortisol Immunoassay Reliability in Cushing Syndrome

Introduction: Twenty-four-hour urinary free cortisol (24h-UFC) is the most used test for follow-up decision-making in patients with Cushing syndrome (CS) under medical treatment. However, 24h-UFC determinations by immunoassays (IA) are commonly overestimated because of steroid metabolites' cross-reaction. It is still uncertain how ketoconazole (KTZ)- and metyrapone (MTP)-induced changes on the urinary steroid metabolites can alter the 24h-UFC*IA determinations' reliability. Methods: 24h-UFC was analyzed by IA and gas chromatography-mass spectrometry (GC-MS) in 193 samples (81 before treatment, 73 during KTZ, and 39 during MTP) from 34 CS patients. In addition, urinary steroidome was analyzed by GC-MS on each patient before and during treatment. Results: Before treatment, 24h-UFC*IA determinations were overestimated by a factor of 1.75 (95% CI 1.60-1.94) compared to those by GC-MS. However, during KTZ treatment, 24h-UFC*IA results were similar (0.98:1) to those by GC-MS (95% CI, 0.83-1.20). In patients taking MTP, IA bias only decreased 0.55, resulting in persistence of an overestimation factor of 1.33:1 (95% CI, 1.09-1.76). High method agreement between GC-MS and IA before treatment (R2 = 0.954) declined in patients under KTZ (R2 = 0.632) but not in MTP (R2 = 0.917). Upper limit normal (ULN) reductions in patients taking KTZ were 27% larger when using 24h-UFC*IA compared to 24h-UFC*GC-MS, which resulted in higher false efficacy and misleading biochemical classification of 15% of patients. Urinary excretion changes of 22 urinary steroid metabolites explained 86% of the 24h-UFC*IA interference. Larger urinary excretion reductions of 6β-hydroxy-cortisol, 20α-dihydrocortisol, and 18-hydroxy-cortisol in patients with KTZ elucidated the higher 24h-UFC*IA bias decrement compared to MTP-treated patients. Conclusion: KTZ and MTP alter the urinary excretion of IA cross-reactive steroid metabolites, thus decreasing the cross-reactive interference of 24h-UFC*IA determinations present before treatment. Consequently, this interference reduction in 24h-UFC*IA leads to loss of method agreement with GC-MS and high risk of overestimating the biochemical impact of KTZ and MTP in controlling CS because of poor reliability of reference ranges and ULN

In vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies

Objective. In this paper, we present a detailed in vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle (SCM), obtained through ultrasound-guided near-infrared time-domain and diffuse correlation spectroscopies. Approach. A total of sixty-five subjects (forty-nine females, sixteen males) among healthy volunteers and thyroid nodule patients have been recruited for the study. Their SCM hemodynamic (oxy-, deoxy- and total hemoglobin concentrations, blood flow, blood oxygen saturation and metabolic rate of oxygen extraction) and optical properties (wavelength dependent absorption and reduced scattering coefficients) have been measured by the use of a novel hybrid device combining in a single unit time-domain near-infrared spectroscopy, diffuse correlation spectroscopy and simultaneous ultrasound imaging. Main results. We provide detailed tables of the results related to SCM baseline (i.e. muscle at rest) properties, and reveal significant differences on the measured parameters due to variables such as side of the neck, sex, age, body mass index, depth and thickness of the muscle, allowing future clinical studies to take into account such dependencies. Significance. The non-invasive monitoring of the hemodynamics and metabolism of the sternocleidomastoid muscle during respiration became a topic of increased interest partially due to the increased use of mechanical ventilation during the COVID-19 pandemic. Near-infrared diffuse optical spectroscopies were proposed as potential practical monitors of increased recruitment of SCM during respiratory distress. They can provide clinically relevant information on the degree of the patient's respiratory effort that is needed to maintain an optimal minute ventilation, with potential clinical application ranging from evaluating chronic pulmonary diseases to more acute settings, such as acute respiratory failure, or to determine the readiness to wean from invasive mechanical ventilation.</p

Comparison of [18F] fluorocholine PET/CT with [99mTc] sestamibi and ultrasonography to detect parathyroid lesions in primary hyperparathyroidism: a prospective study.

Background: Primary hyperparathyroidism is a common endocrine disorder produced by the increase of parathyroid hormone (PTH) due to a benign adenoma of a single parathyroid gland, or as multiple gland hyperplasia, or as a rare malignant tumor. Preoperative imaging scans are frequently necessary for the minimally invasive parathyroidectomies to identify the location of enlarged parathyroid glands and to design the procedure. Methods: The diagnostic reliability of [18F]fluorocholine positron emission tomography/computed tomography (FCH PET/CT), [99mTc]sestamibi [multiplexed ion beam imaging (MIBI)] and cervical ultrasonography was analyzed in 37 patients diagnosed with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. The three preoperative imaging techniques were correlated with intraoperative and histopathological findings as well as changes in biochemical parameters (serum PTH and calcium levels). Statistical analysis was carried out with SPSS version 24.0. Results: In 30 of 37 patients (81.1%), FCH PET/CT correctly localized the pathological gland. In 3 cases of ectopic adenomas, the accuracy of the techniques was 100% (3/3) for FCH PET/CT, 66.7% (2/3) for MIBI, and 33.3% (1/3) for neck ultrasonography. Neither neck ultrasonography nor MIBI were able to locate pathological parathyroid glands in those patients with multiglandular disease, while FCH PET/CT correctly located one patient (1/3, 33.3%) with two adenomas and 3 patients (3/6, 50.0%) with hyperplasia. The three imaging techniques, FCH PET/CT, MIBI and neck ultrasound yielded a sensitivity of 92.1%, 57.9% and 32.4%, a positive predictive value of 94.6%, 84.6% and 78.6%, and a diagnostic accuracy of 96.4%, 85.7% and 79.0%, respectively. Conclusions: In this group of patients diagnosed with primary hyperparathyroidism, FCH PET/CT was superior to MIBI and neck ultrasound in detecting adenomas, particularly in the presence of ectopic glands or multiglandular disease

New Care Models for Transgender People in the Spanish Health System: Demands, Controversies and Reflections

[Resumen] La atención sanitaria a las personas transgénero en España se ha establecido de manera progresiva desde 1999, año en que Andalucía crea la primera unidad multidisciplinar para el tratamiento integral de la reasignación de sexo. Este documento analiza los cambios sociales, las demandas y debates entre usuarios y profesionales y los nuevos modelos de atención sanitaria, y también plantea reflexiones sobre la situación actual. La apertura social en España en la concepción de la diversidad sexual y de género es bastante favorable. Las demandas de los usuarios no son uniformes y no siempre coinciden con los criterios de los profesionales. En algunas comunidades autónomas la asistencia sanitaria se está distanciando del modelo recomendado internacionalmente, que basa la atención en equipos especializados o Unidades de Identidad de Género (UIG). Estos nuevos modelos centran la asistencia en la Atención Primaria, además de en endocrinólogos y pediatras de área sin una evaluación coordinada con Salud Mental. Los principales factores contribuyentes al cambio reciente han sido las demandas desde algunas asociaciones de “despatologización” y “descentralización”. Estos nuevos modelos centran la asistencia en la Atención Primaria, además de en endocrinólogos y pediatras de área sin una evaluación coordinada con Salud Mental. Los profesionales que integran las unidades de género, si bien reconocen la necesidad de una visión amplia de la realidad transgénero, alertan del riesgo que supone tratar a personas trans sin una colaboración de especialistas en Salud Mental o por profesionales de área con escasa experiencia. Además, anticipan que la descentralización no facilita el estudio de grandes cohortes, dificultando el avance del conocimiento y la evaluación contrastada con países del entorno. En resumen, los nuevos modelos sanitarios, aunque ofrecen la atención en proximidad, no garantizan mejoras en la calidad ni promueven el análisis comparado de los resultados.[Abstract] Health care for transgender people in Spain has been progressively established since 1999 when the first multidisciplinary unit for the treatment of sex reassignment was created in Andalusia. In this document, the social changes, the demands and debates of users and professionals, the new models of health care for trans people, and reflections on the current situation, have been analysed. The social openness in Spain regarding sexual and gender diversity has evolved quite positively. The health demands of the transgender users are not uniform and do not always match with the criteria of the professionals. In some Spanish regions, health care is distancing itself from the internationally recommended multidisciplinary model. The new healthcare models have been established under the aegis of primary care and/or endocrinologist in the area, without a required psychological assessment. The main contributing factors for this change of model have been the pressure from some associations with demands for "depathologization" and "decentralization". The professionals of gender units, while recognizing the need for a broader vision of trans reality, warn of the risk of treating trans people without the involvement of mental health specialists or by professionals in proximity with little experience. Moreover, the decentralization would not allow acting on large cohorts, which hinders the advance of knowledge and contrasted evaluations with neighbouring countries. In summary, the new health models, although intended to facilitate care through proximity, do not guarantee improvements in quality and difficult to make a comparative evaluation of the results

The LUCA device: a multi-modal platform combining diffuse optics and ultrasound imaging for thyroid cancer screening

We present the LUCA device, a multi-modal platform combining eight-wavelengthnear infrared time resolved spectroscopy, sixteen-channel diffuse correlation spectroscopy and a clinical ultrasound in a single device. By simultaneously measuring the tissue hemodynamics and performing ultrasound imaging, this platform aims to tackle the low specificity and sensitivit yof the current thyroid cancer diagnosis techniques, improving the screening of thyroid nodules.Here, we show a detailed description of the device, components and modules. Furthermore,we show the device tests performed through well established protocols for phantom validation,and the performance assessment forin vivo. The characterization tests demonstrate that LUCA device is capable of performing high quality measurements, with a precision in determining invivo tissue optical and dynamic properties of better than 3%, and a reproducibility of better than10% after ultrasound-guided probe repositioning, even with low photon count-rates, making it suitable for a wide variety of clinical applications

Nuevos modelos de atención sanitaria para las personas transgénero en el sistema sanitario español: Demandas, controversias y reflexiones

Health care for transgender people in Spain has been progressively established since 1999 when the first multidisciplinary unit for the treatment of sex reassignment was created in Andalusia. In this document, the social changes, the demands and debates of users and professionals, the new models of health care for trans people, and reflections on the current situation, have been analysed. The social openness in Spain regarding sexual and gender diversity has evolved quite positively. The health demands of the transgender users are not uniform and do not always match with the criteria of the professionals. In some Spanish regions, health care is distancing itself from the internationally recommended multidisciplinary model. The new healthcare models have been established under the aegis of primary care and/or endocrinologist in the area, without a required psychological assessment. The main contributing factors for this change of model have been the pressure from some associations with demands for “depathologization” and “decentralization”. The professionals of gender units, while recognizing the need for a broader vision of trans reality, warn of the risk of treating trans people without the involvement of mental health specialists or by professionals in proximity with little experience. Moreover, the decentralization would not allow acting on large cohorts, which hinders the advance of knowledge and contrasted evaluations with neighbouring countries. In summary, the new health models, although intended to facilitate care through proximity, do not guarantee improvements in quality and difficult to make a comparative evaluation of the results.La atención sanitaria a las personas transgénero en España se ha establecido de manera progresiva desde 1999, año en que Andalucía crea la primera unidad multidisciplinar para el tratamiento integral de la reasignación de sexo. Este documento analiza los cambios sociales, las demandas y debates entre usuarios y profesionales y los nuevos modelos de atención sanitaria, y también plantea reflexiones sobre la situación actual. La apertura social en España en la concepción de la diversidad sexual y de género es bastante favorable. Las demandas de los usuarios no son uniformes y no siempre coinciden con los criterios de los profesionales. En algunas comunidades autónomas la asistencia sanitaria se está distanciando del modelo recomendado internacionalmente, que basa la atención en equipos especializados o Unidades de Identidad de Género (UIG). Estos nuevos modelos centran la asistencia en la Atención Primaria, además de en endocrinólogos y pediatras de área sin una evaluación coordinada con Salud Mental. Los principales factores contribuyentes al cambio reciente han sido las demandas desde algunas asociaciones de “despatologización” y “descentralización”. Los profesionales que integran las unidades de género, si bien reconocen la necesidad de una visión amplia de la realidad transgénero, alertan del riesgo que supone tratar a personas trans sin una colaboración de especialistas en Salud Mental o por profesionales de área con escasa experiencia. Además, anticipan que la descentralización no facilita el estudio de grandes cohortes, dificultando el avance del conocimiento y la evaluación contrastada con países del entorno. En resumen, los nuevos modelos sanitarios, aunque ofrecen la atención en proximidad, no garantizan mejoras en la calidad ni promueven el análisis comparado de los resultados

Surgical outcomes in the pheochromocytoma surgery. Results from the PHEO-RISK STUDY.

To identify presurgical and surgical risk factors for postsurgical complications in the pheochromocytoma surgery. A retrospective study of pheochromocytomas submitted to surgery in ten Spanish hospitals between 2011 and 2021. Postoperative complications were classified according to Clavien-Dindo scale. One hundred and sixty-two surgeries (159 patients) were included. Preoperative antihypertensive blockade was performed in 95.1% of the patients, being doxazosin in monotherapy (43.8%) the most frequent regimen. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more frequently (49.4% vs 25.0%, P = 0.003) than patients treated with phenoxybenzamine, but no differences in the rate of intraoperative and postsurgical complications were observed. However, patients treated with phenoxybenzamine had a longer hospital stay (12.2 ± 11.16 vs 6.2 ± 6.82, P  Preoperative medical treatment and postsurgical monitoring of pheochromocytoma should be especially careful in patients with diabetes, cerebrovascular disease, higher levels of plasma glucose and urine free metanephrine and norepinephrine, and with pheochromocytomas >5 cm, due to the higher risk of postsurgical complications

Predictive model of pheochromocytoma based on the imaging features of the adrenal tumours.

The purpose of our study was to develop a predictive model to rule out pheochromocytoma among adrenal tumours, based on unenhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) features. We performed a retrospective multicentre study of 1131 patients presenting with adrenal lesions including 163 subjects with histological confirmation of pheochromocytoma (PHEO), and 968 patients showing no clinical suspicion of pheochromocytoma in whom plasma and/or urinary metanephrines and/or catecholamines were within reference ranges (non-PHEO). We found that tumour size was significantly larger in PHEO than non-PHEO lesions (44.3 ± 33.2 versus 20.6 ± 9.2 mm respectively; P

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society