The intracellular angiotensin system buffersdeleterious effects of the extracellular paracrine system

The‘classical’renin–angiotensin system (RAS) is a circulating system that controls blood pressure. Local/paracrine RAS,identified in a variety of tissues, including the brain, is involved in different functions and diseases, and RAS blockers arecommonly used in clinical practice. A third type of RAS (intracellular/intracrine RAS) has been observed in some types of cells,including neurons. However, its role is still unknown. The present results indicate that in brain cells the intracellular RAScounteracts the intracellular superoxide/H2O2and oxidative stress induced by the extracellular/paracrine angiotensin II acting onplasma membrane receptors. Activation of nuclear receptors by intracellular or internalized angiotensin triggers a number ofmechanisms that protect the cell, such as an increase in the levels of protective angiotensin type 2 receptors, intracellularangiotensin, PGC-1αand IGF-1/SIRT1. Interestingly, this protective mechanism is altered in isolated nuclei from brains of agedanimals. The present results indicate that at least in the brain, AT1 receptor blockers acting only on the extracellular or paracrineRAS may offer better protection of cellsWe thank Dr. Wei-Dong Le for providing the MES 23.5dopaminergic cell line, Dr. Manuel Serrano and Dr. Ruben Nogueiras for providing thetransgenic mice overexpressing SIRT1, and Dr. Daniel Henrion for providing the AT2KO mice. We thank Pilar Aldrey, Iria Novoa and Cristina Gianzo for their technicalassistance. This study was funded by the Spanish Ministry of Economy andCompetitiveness (BFU2015-70523), Spanish Ministry of Health (RD12/0019/0020,RD16/0011/0016 and CIBERNED), Galician Government (XUGA, GRC2014/002ED431G/05 and CIMUS accreditation 2016‐2019) and FEDER (Regional EuropeanDevelopment Fund)S

Groundwater intensive use and mining in south-eastern peninsular Spain: Hydrogeological, economic and social aspects

Intensive groundwater development is a common circumstance in semiarid and arid areas. Often abstraction exceeds recharge, thus continuously depleting reserves. There is groundwater mining when the recovery of aquifer reserves needs more than 50 years. The MASE project has been carried out to compile what is known about Spain and specifically about the south-eastern Iberian Peninsula and the Canary Islands. The objective was the synthetic analysis of available data on the hydrological, economic, managerial, social, and ethical aspects of groundwater mining. Since the mid-20th century, intensive use of groundwater in south-eastern Spain allowed extending and securing the areas with traditional surface water irrigation of cash crops and their extension to former dry lands, taking advantage of good soils and climate. This fostered a huge economic and social development. Intensive agriculture is a main activity, although tourism plays currently an increasing economic role in the coasts. Many aquifers are relatively high yielding small carbonate units where the total groundwater level drawdown may currently exceed 300 m. Groundwater storage depletion is estimated about 15 km3. This volume is close to the total contribution of the Tagus-Segura water transfer, but without large investments paid for with public funds. Seawater desalination complements urban supply and part of cash crop cultivation. Reclaimed urban waste water is used for irrigation. Groundwater mining produces benefits but associated to sometimes serious economic, administrative, legal and environmental problems. The use of an exhaustible vital resource raises ethical concerns. It cannot continue under the current legal conditions. A progressive change of water use paradigm is the way out, but this is not in the mind of most water managers and politicians. The positive and negative results observed in south-eastern Spain may help to analyse other areas under similar hydrogeological conditions in a less advanced stage of water use evolution

Temporal headache and jaw claudication may be the key for the diagnosis of giant cell arteritis

Temporal artery biopsy (TAB) is a surgical procedure with a low positive yield. The purpose of this study is to determine which variables are the most important in the giant cell arteritis (GCA) diagnosis. The objective of this evaluation is to improve the percentage of positive temporal artery biopsy and if possible, avoid the biopsy in some cases. A retrospective clinical study consisted of 90 patients who had undergone TAB at the Río Hortega Hospital (Spain) from January 2009 to December 2016. Clinical findings, erythrocyte sedimentation rates (ESR) and other laboratory parameters, American College of Rheumatology (ACR) criteria for GCA score and biopsy results were recorded. Nineteen (21.1%) biopsies were positive for GCA. The mean age in positive TAB was 78.6 years old (SD 7.93), and 73.7% were female. Presence of temporal headache (p = 0.003), jaw claudication (p = 0.001), abnormal artery exploration (p = 0.023), elevated erythrocyte sedimentation rate (p = 0.035), CRP (p = 0.018) and platelets (p = 0.042), were significantly associated with GCA. Multivariate logistic regression revealed that the best predictors for the diagnosis of GCA are headache and jaw claudication, adjusted by sex, age, and temporal exploration. TAB has benefit only for patients who score a 2 or 3 on the ACR criteria for GCA without biopsy. These findings highlight the need for a better diagnostic strategy for patients with suspected temporal arteritis

SEPAR Recommendations for COVID-19 Vaccination in Patients With Respiratory Diseases

La Sociedad Espanola de Neumología y Cirugía Torácica (SEPAR) ha elaborado este documento de reco mendaciones sobre la vacuna para la COVID-19 en las enfermedades respiratorias, con el objetivo de ayudar al personal sanitario en la toma de decisiones sobre cómo actuar en la vacunación de estos pacientes. Las recomendaciones han sido elaboradas por un grupo de expertos en la materia, tras la revisión de la literatura recopilada hasta el 7 de marzo del 2021, y de la información aportada por distintas sociedades científicas, agencias del medicamento y estrategias de organismos gubernamentales hasta esa fecha. Podemos concluir que las vacunas para la COVID-19 no solo son seguras y eficaces, sino que, en aquellos pacientes vulnerables con enfermedades respiratorias crónicas, son prioritarias. Además, la implicación activa de los profesionales sanitarios que manejan estas patologías en la estrategia de vacunación es clave para lograr una buena adherencia y coberturas vacunales elevadas.The Spanish Society of Pneumonology and Thoracic Surgery (SEPAR) has elaborated this document of recommendations for COVID-19 vaccination in patients with respiratory diseases aimed to help healthcare personnel make decisions about how to act in case of COVID-19 vaccination in these patients. The recommendations have been developed by a group of experts in this field after reviewing the materials published up to March 7, 2021, the information provided by different scientific societies, drug agencies and the strategies of the governmental bodies up to this date. We can conclude that COVID-19 vaccines are not only safe and effective, but also prior in vulnerable patients with chronic respiratory diseases. In addition, an active involvement of healthcare professionals, who manage these diseases, in the vaccination strategy is the key to achieve good adherence and high vaccination coverage

Lung cancer survival in never-smokers and exposure to residential radon: results of the LCRINS study

We aimed to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential-radon, age, histological type, and diagnostic stage. We included lung cancer cases diagnosed in a multicentre, hospital-based, case-control-study of never-smoker patients, diagnosed from January-2011 to March-2015 (Lung Cancer Research In Never Smokers study). 369 never-smokers (79% women; median age 71 years; 80% adenocarcinoma; 66% stage IV) were included. Median overall survival, and at one, 3 and 5 years of diagnosis was 18.3 months, 61%, 32% and 22%, respectively. Higher median survival rates were obtained for: younger age, adenocarcinoma, actionable mutations, and earlier-stage at diagnosis. Higher indoor radon showed a higher risk of death in multivariate analysis. Median lung cancer survival in never-smokers seems higher than that in ever-smokers. Patients with actionable mutations have a significantly higher survival. Higher indoor-radon exposure has a negative effect on survivalThis paper was funded by the following competitive research grants awarded to the individual case-control studies, which are part of this pooled study: Galician Regional Authority (Xunta de Galicia): 10CSA208057PR “Risk factors of lung cancer in never smokers: a multicentre case-control study in the Northwest of Spain.” 2010. Spain; Carlos III Institute of Health (Instituto de Salud Carlos III), Ministry of Science and Innovation of Spain, grant number PI03/1248. 2003. Spain; Carlos III Institute of Health (grant FIS 92/0176) and the Galician Regional Health Authority (grant XUGA 91010). 1992. Spain; Galician Regional Authority: grant number XUGA 208001B93. 1993; Carlos III Institute of Health, Ministry of Science and Innovation of Spain, grant number PI13/01765. 2013. Spain; ISCIII - PI15/01211 - Cofinanciado FEDER. Spain.This paper was funded by the following competitive research grants awarded to the individual case-control studies, which are part of this pooled study: • Galician Regional Authority (Xunta de Galicia): 10CSA208057PR “Risk factors of lung cancer in never smokers: a multicentre case-control study in the Northwest of Spain.” 2010. Spain. • Carlos III Institute of Health (Instituto de Salud Carlos III), Ministry of Science and Innovation of Spain, grant number PI03/1248. 2003. Spain. • Carlos III Institute of Health (grant FIS 92/0176) and the Galician Regional Health Authority (grant XUGA 91010). 1992. Spain. • Galician Regional Authority: grant number XUGA 208001B93. 1993. • Carlos III Institute of Health, Ministry of Science and Innovation of Spain, grant number PI13/01765. 2013. Spain. • ISCIII - PI15/01211 - Cofinanciado FEDER. Spain

A logistic model for the detection of circulating tumour cells in human metastatic colorectal cancer

The accuracy in the diagnosis of metastatic colorectal cancer (mCRC) represents one of the challenges in the clinical management of patients. The detection of circulating tumour cells (CTC) is becoming a promising alternative to current detection techniques, as it focuses on one of the players of the metastatic disease and it should provide with more specific and sensitive detection rates. Here, we describe an improved method of detection of CTC from mCRC patients by combining immune-enrichment, optimal purification of RNA from very low cell numbers, and the selection of accurate PCR probes. As a result, we obtained a logistic model that combines GAPDH and VIL1 normalized to CD45 rendering powerful results in the detection of CTC from mCRC patients (AUROC value 0.8599). We further demonstrated the utility of this model at the clinical setting, as a reliable prognosis tool to determine progression-free survival in mCRC patients. Overall, we developed a strategy that ameliorates the specificity and sensitivity in the detection of CTC, resulting in a robust and promising logistic model for the clinical management of metastatic colorectal cancer patients.Ministerio de Sanidad, Consumo y Bienestar Social. Beca número: CP08/00142Programa Comisión Europea Fondo Europeo de Desarollo Regional (FEDER

Connected Insulin Pens and Caps : An Expert's Recommendation from the Area of Diabetes of the Spanish Endocrinology and Nutrition Society (SEEN)

Undoubtedly, technological advances have revolutionised diabetes management in recent years. The development of advanced closed hybrid loop insulin pumps or continuous glucose monitoring (CGM) systems, among others, have increased the quality of life and improved glycaemic control of people with diabetes. However, only some patients have access to such technology, and only some want to use it. CGM has become much more widespread, but in terms of insulin delivery, most people with type 1 diabetes (T1D) and almost all people with type 2 diabetes (T2D) on insulin therapy are treated with multiple-dose insulin injections (MDI) rather than an insulin pump. For these patients, using connected insulin pens or caps has shown benefits in reducing missed insulin injections and promoting correct administration over time. In addition, using these devices improves the quality of life and user satisfaction. The integration of insulin injection and CGM data facilitates both users and the healthcare team to analyse glucose control and implement appropriate therapeutic changes, reducing therapeutic inertia. This expert's recommendation reviews the characteristics of the devices marketed or in the process of being marketed and their available scientific evidence. Finally, it suggests the profile of users and professionals who would benefit most, the barriers to its generalisation and the changes in the care model that implementing these devices can bring with it

Factors associated with therapeutic response in acromegaly diagnosed in the elderly in Spain

ContextSome reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. ObjectiveThis study aimed at identifying predictors of response to SRL in elderly patients. DesignMulticentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. ResultsOne-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 +/- 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean +/- SD) were 2.7 +/- 1.4 and 11.0 +/- 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 +/- 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis <= 6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4-91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01-0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71-0.94). ConclusionsThe most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis <= 6 ng/ml and female gender, but not age per se, were associated with a greater chance of response to SRL