Determination of the aldosterone/plasma renin activity ratio for the screening of primary hyperaldosteronism in essential hypertension: a multicentric study

El hiperaldosteronismo primario (HAP) es una afección caracterizada por la producción inapropiadamente elevada y una relativa autonomía del sistema renina-angiotensina. Estimaciones previas, basadas sólo en la evaluación de hipertensos con hipokalemia, consideraban al HAP como una causa poco frecuente de hipertensión (1%). Sin embargo, estudios actuales fundamentados en el cálculo de la relación aldosterona/ actividad de renina plasmática (RAA) arrojan una incidencia mayor (5-10%), siendo la hipertensión arterial (HTA) normokalémica la presentación más frecuente. Dada la amplitud de los valores de corte de la RAA, el Departamento de Suprarrenal de SAEM diseñó un estudio multicéntrico prospectivo en una población de Argentina con el objetivo de establecer nuestro propio valor y determinar así la prevalencia de HAP. Fueron estudiados 353 individuos de ambos sexos, 104 controles normotensos, sin antecedentes familiares de HTA y 249 pacientes hipertensos. Se indicó dieta normosódica y la suspensión de antihipertensivos que interfieran con el eje mineralocorticoideo. Las determinaciones de la actividad de renina plasmática (ARP), DIA-SorinRIA, y de aldosterona, RIA-DPC, fueron realizadas en un único laboratorio. Se realizó ionograma y se evaluaron parámetros clínicos y bioquímicos de síndrome metabólico. La RAA calculada según el percentilo 95 en los controles, fue establecida en la cifra de 36 como valor de corte para sospechar HAP en los hipertensos, requiriéndose una concentración de aldosterona >15 ng/ml. Con una RAA≥36, se realizaron pruebas confirmatorias de sobrecarga salina o de fludrocortisona. La RAA fue ≥36 en 31/249 pacientes, confirmándose HAP en 8 (7 adenomas y 1 hiperplasia), con una prevalencia del 3.2%. Los restantes no completaron estudios confirmatorios. La presencia de síndrome metabólico fue similar en los hipertensos con y sin HAP. En conclusión, este primer estudio multicéntrico argentino determinó nuestro valor de corte de la RAA en 36. Su aplicación permitió establecer una prevalencia de HAP del 3,2% que, aunque podría estar subestimada, resulta significativamente mayor que la previa histórica y concuerda con la incidencia referida en la bibliografía.Primary hyperaldosteronism (PHA) or Conn's disease was classically suspected in the presence of hypertension (H) and hypokalemia. It was previously considered as a rare cause of H, being reported in only 1% of hypertensive patients. It can be caused by an adrenal adenoma (the former usual presentation) or by adrenal hyperplasia. But since the use of the aldosterone/plasma renin activity ratio (AAR) as the screening method in the last years, it is currently considered as almost the most frequent cause of secondary H., accounting for 5-10% of essential H. Plasma rennin activity (PRA) determination is a laborious procedure with low reproducibility and it directly affects the AAR; thus each laboratory must assess its own cut-off value. Therefore, in the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM), we performed this multicentric prospective study of a population of Argentina with the aim of assessing our own AAR cut-off level in normotensive controls in order to apply it for PHA screening in essential hypertensive patients. We studied 353 adult subjects: 104 controls, aged 45,18 ± 13,78 years-old ( X±SD), with no history of arterial hypertension in their first-degree relatives and with two separate day-registry of blood pressure≤ 139/85 mmHg and 249 hypertensive patients, aged 51± 13,6 years-old ( X ± SD), with arterial blood pressure≥ 140/90 mmHg in the sitting position. Subjects with cardiac, renal, hepatic and neurological diseases were excluded as well as those with Cushing´s syndrome, hyperthyroidism, untreated hypothyroidism, diabetes mellitus and patients under glucocorticoids, oral contraceptive pills or estrogen therapy. A normal sodium diet was indicated and potassium was supplemented when needed. Blood was withdrawn between 8 and 10:00 a.m. with the subjects in the upright position. Aldosterone (A) was determined by DPC radioimmunoassay (RIA) and PRA, by DIA-Sorin RIA. The A normal levels are 4-30 ng/dl for ambulatory individuals on a normal sodium diet and the PRA normal values are < 3,3 ng/ml/h. In order to avoid false positive results in the hypertensive group, AAR was calculated when A was above 15 ng/dl. We measured the waist circumference and we determined the body mass index. Blood sodium, potassium, calcium, urea, creatinine, cholesterol, HDL-C, LDL-C, triglyceride and liver function tests were performed. Statistical Analysis and Results Since the AAR variable showed a non-normal distribution, the cut-off value was considered as the 95th percentile in the control group, which was calculated as 36. This is also in accordance to the function of the empirical distribution of Collings and Hamilton. In our 249 hypertensive patients, 31 had an AAR ≥ 36. PHA was confirmed in 8: seven has an adrenal adenoma and one had hyperplasia. The prevalence of PHA in our population was 3,2 %, with a 95th confidence interval ranging from 1,4 to 6,2 %. In the remaining 23 patients, confirmatory tests could not be completed. There was no correlation between the severity of the hypertension and the AAR value, with no statistical significant differences between those with or without PHA. Likewise, we found no correlation between PRA and advancing age. In hypertensive patients, metabolic syndrome was more prevalent than in controls, but it was present to the same extent in those with or without PHA. Conclusions To our knowledge, this is the first multicentric study performed in Argentina to determine the aldosterone/ plasma renin activity ratio in our normotensive control population. Our AAR value of 36 agrees with the levels reported in the international literature: thus an AAR ≥ 36 along with an aldosterone ≥ 15 ng/ml in hypertensive patients lead us to suspect PHA and to perform confirmatory tests. Applying these criteria, we found a prevalence of 3,2% of PHA in essential HTA. It is possible that this value may be underestimated due to the fact that confirmatory tests could not be completed in all the hypertensive subjects with an AAR≥ 36. In spite of this, our prevalence is significantly greater than the historical one and it lies in the range reported in the literature.Fil: Pardes, E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Belli, S.. Hospital Dr. C. Durand; ArgentinaFil: Cornaló, D.. Hospital Rivadavia; ArgentinaFil: Contreras, Liliana Noemi. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Costa, L.. Hospital Dr. A. Posadas; ArgentinaFil: Chervin. R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Damilano, S.. Laboratorio de Bioanalítica; ArgentinaFil: Fenili, C.. Laboratorio de Bioanalítica; ArgentinaFil: Gómez, R. M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Leal Reyna, M.. Complejo Médico Policial "Churruca"; ArgentinaFil: Lupi, S.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Martínez, M.. Hospital Francés; ArgentinaFil: Nofal, M.. Clínica Bazterrica; ArgentinaFil: Ruibal, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; Argentin

Dal bilancio sociale 2005 ai progetti per il futuro

Il Bilancio sociale è uno strumento adottato dalle amministrazioni pubbliche per rendere note, in modo chiaro e sintetico, le scelte fatte, le azioni realizzate, le risorse impiegate e i risultati ottenuti. Attraverso Il Bilancio sociale l'Ente Parco si prefigge, soprattutto, di fornire i dati sui i caratteri geografici dell'area, presentare la gestione dell'area protetta e acquisire un nuovo modello di rendicontazione che permetta di costruire un quadro completo sulle iniziative e le attività svolt

Dal bilancio sociale 2005 ai progetti per il futuro

Il Bilancio sociale è uno strumento adottato dalle amministrazioni pubbliche per rendere note, in modo chiaro e sintetico, le scelte fatte, le azioni realizzate, le risorse impiegate e i risultati ottenuti. Attraverso Il Bilancio sociale l’Ente Parco si prefigge, soprattutto, di fornire i dati sui i caratteri geografici dell’area, presentare la gestione dell’area protetta e acquisire un nuovo modello di rendicontazione che permetta di costruire un quadro completo sulle iniziative e le attività svolte

Polarized white light from hybrid organic/III-nitrides grating structures.

Highly polarised white light emission from a hybrid organic/inorganic device has been achieved. The hybrid devices are fabricated by means of combining blue InGaN-based multiple quantum wells (MQWs) with a one-dimensional (1D) grating structure and down-conversion F8BT yellow light emitting polymer. The 1D grating structure converts the blue emission from unpolarised to highly polarised; Highly polarised yellow emission has been achieved from the F8BT polymer filled and aligned along the periodic nano-channels of the grating structure as a result of enhanced nano-confinement. Optical polarization measurements show that our device demonstrates a polarization degree of up to 43% for the smallest nano-channel width. Furthermore, the hybrid device with such a grating structure allows us to achieve an optimum relative orientation between the dipoles in the donor (i.e., InGaN/GaN MQWs) and the diploes in the acceptor (i.e., the F8BT), maximizing the efficiency of non-radiative energy transfer (NRET) between the donor and the acceptor. Time-resolved micro photoluminescence measurements show a 2.5 times enhancement in the NRET efficiency, giving a maximal NRET efficiency of 90%. It is worth highlighting that the approach developed paves the way for the fabrication of highly polarized white light emitters

Deep RNA Sequencing Reveals Novel Cardiac Transcriptomic Signatures for Physiological and Pathological Hypertrophy

Although both physiological hypertrophy (PHH) and pathological hypertrophy (PAH) of the heart have similar morphological appearances, only PAH leads to fatal heart failure. In the present study, we used RNA sequencing (RNA-Seq) to determine the transcriptomic signatures for both PHH and PAH. Approximately 13–20 million reads were obtained for both models, among which PAH showed more differentially expressed genes (DEGs) (2,041) than PHH (245). The expression of 417 genes was barely detectable in the normal heart but was suddenly activated in PAH. Among them, Foxm1 and Plk1 are of particular interest, since Ingenuity Pathway Analysis (IPA) using DEGs and upstream motif analysis showed that they are essential hub proteins that regulate the expression of downstream proteins associated with PAH. Meanwhile, 52 genes related to collagen, chemokines, and actin showed opposite expression patterns between PHH and PAH. MAZ-binding motifs were enriched in the upstream region of the participating genes. Alternative splicing (AS) of exon variants was also examined using RNA-Seq data for PAH and PHH. We found 317 and 196 exon inclusions and exon exclusions, respectively, for PAH, and 242 and 172 exon inclusions and exclusions, respectively for PHH. The AS pattern was mostly related to gains or losses of domains, changes in activity, and localization of the encoded proteins. The splicing variants of 8 genes (i.e., Fhl1, Rcan1, Ndrg2, Synpo, Ttll1, Cxxc5, Egfl7, and Tmpo) were experimentally confirmed. Multilateral pathway analysis showed that the patterns of quantitative (DEG) and qualitative (AS) changes differ depending on the type of pathway in PAH and PHH. One of the most significant changes in PHH is the severe downregulation of autoimmune pathways accompanied by significant AS. These findings revealed the unique transcriptomic signatures of PAH and PHH and also provided a more comprehensive understanding at both the quantitative and qualitative levels

Monolithically integrated white light LEDs on (11-22) semi-polar GaN templates

Carrier transport issues in a (11–22) semi-polar GaN based white light emitting diode (consisting of yellow and blue emissions) have been investigated by detailed simulations, demonstrating that the growth order of yellow and blue InGaN quantum wells plays a critically important role in achieving white emission. The growth order needs to be yellow InGaN quantum wells first and then a blue InGaN quantum well after the growth of n-type GaN. The fundamental reason is due to the poor hole concentration distribution across the whole InGaN quantum well region. In order to effectively capture holes in both the yellow InGaN quantum wells and the blue InGaN quantum well, a thin GaN spacer has been introduced prior to the blue InGaN quantum well. The detailed simulations of the band diagram and the hole concentration distribution across the yellow and the blue quantum wells have been conducted, showing that the thin GaN spacer can effectively balance the hole concentration between the yellow and the blue InGaN quantum wells, eventually determining their relative intensity between the yellow and the blue emissions. Based on this simulation, we have demonstrated a monolithically multi-colour LED grown on our high quality semi-polar (11–22) GaN templates

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p&lt;0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p&lt;0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved