Recommendations of the GARIN group for dietary managing of patient with chronic kidney disease

[ES] Introducción y objetivos: en el tratamiento dietético de los pacientes con enfermedad renal crónica (ERC) existen muchas áreas de incertidumbre. El grupo de trabajo GARIN tiene como objetivo defi nir su posición en este campo. Material y métodos: revisión bibliográfi ca previa y reunión presencial en la que se discutieron y contestaron preguntas específi cas sobre el tema. Resultados: la actuación terapéutica debe ser individualizada y atendiendo al grado de enfermedad renal que presente el paciente y a sus comorbilidades. En cuanto a la terapia médica nutricional, nuestro grupo propone tres niveles diferentes de actuación, en los que las recomendaciones de ingesta proteica, fi bra, ácidos grasos o potasio son distintas. Además, sugerimos utilizar el concepto ratio fósforo/proteína en el ajuste de la dieta del paciente con ERC. Damos recomendaciones en cuanto al tratamiento en diabetes y en suplementación artifi cial. Conclusiones: estas recomendaciones aportan respuestas concretas sobre cuestiones comunes en la asistencia a pacientes con ERC.[EN] Background and objectives: by means of this update, the GARIN working group aims to defi ne its position regarding the dietary treatment of patients with chronic kidney disease (CKD). In this area there are many aspects of uncertainty. Material and methods: bibliographical review and specifi c questions in advance were discussed and answered at a meeting in the form of conclusions. Results: the therapeutic action must be individualized and taking into account the degree of renal failure that the patient presents and their comorbidities. Regarding nutritional medical therapy, our group proposes three different levels of action, in which the recommendations of protein intake, fi ber, fatty acids or potassium are different. In addition, we suggest using the phosphorus/protein ratio concept in adjusting the diet of the patient with CKD. We give recommendations regarding treatment in diabetes and artifi cial supplementation. Conclusions: these recommendations about dietary issues in patients with CKD can add value to clinical work.Nestlé Health Nutrition cubrió todos los gastos de transporte y de alquiler de salones para las sesiones físicas, pero no ha tomado parte en el desarrollo, diseño o manuscrito del artículo

Variations in diabetes remission rates after bariatric surgery in Spanish adults according to the use of different diagnostic criteria for diabetes

Abstract Background There are multiple criteria to define remission of type 2 diabetes (DM2) after bariatric surgery but there is not a specific one widely accepted. Our objectives were to compare diagnostic criteria for DM2 remission after bariatric surgery: Criteria from Spanish scientific associations (SEEN/SEEDO/SED) and from the American Diabetes Association (ADA). We also aim to analyse the degree of correlation between these sets of criteria. Methods Retrospective observational study in 127 patients undergoing bariatric surgery in a single centre (Hospital Universitario Reina Sofía, Córdoba, Spain) between January 2001 and December 2009. We analysed DM2 remission following bariatric surgery comparing DM2 diagnostic criteria approved by Spanish scientific associations and ADA criteria. Results In total, 62.2% of patients were women; mean age was 47.1 years. Following surgery, 52% achieved complete remission according to ADA criteria, and 63.8% following the criteria approved by Spanish associations (p = 0.001);18.9 and 8.7%, respectively, showed partial remission (p = 0.007), and 29.1 and 27.6% no remission, according to the criteria approved by each association (p = 0.003). There was good correlation between both sets of criteria (Rho 0.781; p < 0.001). Conclusions In our series, using more stringent criteria for defining DM2 remission (ADA criteria) results in a lower rate of remission, although we found a a high degree of correlation between both sets of criteria

Randomized Study to Evaluate the Impact of Telemedicine Care in Patients With Type 1 Diabetes With Multiple Doses of Insulin and Suboptimal HbA1c in Andalusia (Spain): PLATEDIAN Study

Diabetes Group of SAEDYN (Andalusian Society of Endocrinology, Diabetes, and Nutrition).[Objective] To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes.[Research design and methods] PLATEDIAN (Telemedicine on Metabolic Control in Type 1 Diabetes Mellitus Andalusian Patients) (NCT03332472) was a multicenter, randomized, 6-month follow-up, open-label, parallel-group controlled study performed in patients with type 1 diabetes with suboptimal metabolic control (HbA1c <8% [<64 mmol/mol]), treated with multiple daily injections. A total of 388 patients were assessed for eligibility; 379 of them were randomized 1:1 to three face-to-face visits (control cohort [CC]) (n = 167) or the replacement of an intermediate face-to-face visit by a telemedicine visit using Diabetic (intervention cohort [IC]) (n = 163). The primary efficacy end point was the mean change of HbA1c levels from baseline to month 6. Other efficacy and safety end points were mean blood glucose, glucose variability, episodes of hypoglycemia and hyperglycemia, patient-reported outcomes, and physicians’ satisfaction.[Results] At month 6, the mean change in HbA1c levels was −0.04 ± 0.5% (−0.5 ± 5.8 mmol/mol) in the CC and 0.01 ± 0.6% (0.1 ± 6.0 mmol/mol) in the IC (P = 0.4941). The number of patients who achieved HbA1c <7% (<53 mmol/mol) was 73 and 78 in the CC and IC, respectively. Significant differences were not found regarding safety end points at 6 months. Changes in HRQoL between the first visit and final visit did not differ between cohorts, and, regarding fear of hypoglycemia (FH-15 score ≥28), statistically significant differences observed at baseline remained unchanged at 6 months (P < 0.05).[Conclusions] The use of telemedicine in patients with type 1 diabetes with HbA1c <8% (<64 mmol/mol) provides similar efficacy and safety outcomes as face-to-face visits.This study was sponsored by the Andalusian Society of Endocrinology, Diabetes, and Nutrition (SAEDYN). A.M.-G. was the recipient of a postdoctoral grant (Juan Rodes JR 17/00023) from the Spanish Ministry of Economy and Competitiveness

Catecholaminergic Crisis After a Bleeding Complication of COVID-19 Infection: A Case Report.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents in some cases with hemostatic and thrombotic complications. Pheochromocytomas are unusual, though potentially lethal tumors. Herein we describe the first case of hemorrhage in a pheochromocytoma related to SARS-CoV-2 infection. A 62-year-old man consulted for syncope, fever, and palpitations. He was diagnosed with SARS-CoV-2 pneumonia and presented with a hemorrhage in a previously unknown adrenal mass, which resulted in a catecholaminergic crisis. Medical treatment and surgery were required for symptom control and stabilization. We hereby alert clinicians to watch for additional/unreported clinical manifestations in COVID-19 infection

Association between radiological parameters and clinical and molecular characteristics in human somatotropinomas

Abstract Acromegaly is a rare but severe disease, originated in 95% of cases by a growth hormone-secreting adenoma (somatotropinoma) in the pituitary. Magnetic resonance imaging (MRI) is a non-invasive technique used for the diagnosis and prognosis of pituitary tumours. The aim of this study was to determine whether the use of T2-weighted signal intensity at MRI could help to improve the characterisation of somatotropinomas, by analysing its relationship with clinical/molecular features. An observational study was implemented in a cohort of 22 patients (mean age = 42.1 ± 17.2 years; 59% women; 95% size>10 mm). Suprasellar-extended somatotropinomas presented larger diameters vs. non-extended tumours. T2-imaging revealed that 59% of tumours were hyperintense and 41% isointense adenomas, wherein hyperintense were more invasive (according to Knosp-score) than isointense adenomas. A higher proportion of hyperintense somatotropinomas presented extrasellar-growth, suprasellar-growth and invasion of the cavernous sinus compared to isointense adenomas. Interestingly, somatostatin receptor-3 and dopamine receptor-5 (DRD5) expression levels were associated with extrasellar and/or suprasellar extension. Additionally, DRD5 was also higher in hyperintense adenomas and its expression was directly correlated with Knosp-score and with tumour diameter. Hence, T2-weighted MRI on somatotropinomas represents a potential tool to refine their diagnosis and prognosis, and could support the election of preoperative treatment, when required

Statins Directly Regulate Pituitary Cell Function and Exert Antitumor Effects in Pituitary Tumors

[Introduction] Pituitary neuroendocrine tumors (PitNETs), the most abundant of all intracranial tumors, entail severe comorbidities. First-line therapy is transsphenoidal surgery, but subsequent pharmacological therapy is often required. Unfortunately, many patients are/become unresponsive to available drugs (somatostatin analogues [SSAs]/dopamine agonists), underscoring the need for new therapies. Statins are well-known drugs commonly prescribed to treat hyperlipidemia/cardiovascular diseases, but can convey additional beneficial effects, including antitumor actions. The direct effects of statins on normal human pituitary or PitNETs are poorly known. Thus, we aimed to explore the direct effects of statins, especially simvastatin, on key functional parameters in normal and tumoral pituitary cells, and to evaluate the combined effects of simvastatin with metformin (MF) or SSAs.[Methods] Effects of statins in cell proliferation/viability, hormone secretion, and signaling pathways were evaluated in normal pituitary cells from a primate model (Papio anubis), tumor cells from corticotropinomas, somatotropinomas, nonfunctioning pituitary tumors, and PitNET cell-lines (AtT20/GH3-cells).[Results] All statins decreased AtT20-cell proliferation, simvastatin showing stronger effects. Indeed, simvastatin reduced cell viability and/or hormone secretion in all PitNETs subtypes and cell-lines, and ACTH/GH/PRL/FSH/LH secretion (but not expression), in primate cell cultures, by modulating MAPK/PI3K/mTOR pathways and expression of key receptors (GH-releasing hormone-receptor/ghrelin-R/Kiss1-R) regulating pituitary function. Addition of MF or SSAs did not enhance simvastatin antitumor effects.[Conclusion] Our data reveal direct antitumor effects of simvastatin on PitNET-cells, paving the way to explore these compounds as a possible tool to treat PitNETs

Biguanides Exert Antitumoral Actions in Pituitary Tumor Cells Through AMPK-Dependent and -Independent Mechanisms

[Context] Pituitary neuroendocrine tumors (PitNETs) are a commonly underestimated pathology in terms of incidence and associated morbimortality. Currently, an appreciable subset of patients are resistant or poorly responsive to the main current medical treatments [i.e., synthetic somatostatin analogs (SSAs) and dopamine agonists]. Thus, development and optimization of novel and available medical therapies is necessary. Biguanides (metformin, buformin, and phenformin) are antidiabetic drugs that exert antitumoral actions in several tumor types, but their pharmacological effects on PitNETs are poorly known.[Objective] We aimed to explore the direct effects of biguanides on key functions (cell viability, hormone release, apoptosis, and signaling pathways) in primary cell cultures from human PitNETs and cell lines. Additionally, we evaluated the effect of combined metformin with SSAs on cell viability and hormone secretion.[Design] A total of 13 corticotropinomas, 13 somatotropinomas, 13 nonfunctioning PitNETs, 3 prolactinomas, and 2 tumoral pituitary cell lines (AtT-20 and GH3) were used to evaluate the direct effects of biguanides on cell viability, hormone release, apoptosis, and signaling pathways.[Results] Biguanides reduced cell viability in all PitNETs and cell lines (with phenformin being the most effective biguanide) and increased apoptosis in somatotropinomas. Moreover, buformin and phenformin, but not metformin, reduced hormone secretion in a cell type–specific manner. Combination metformin/SSA therapy did not increase SSA monotherapy effectiveness. Effects of biguanides on PitNETs could involve the modulation of AMP-activated protein kinase–dependent ([Ca2+]i, PI3K/Akt) and independent (MAPK) mechanisms.[Conclusion] Altogether, our data unveil clear antitumoral effects of biguanides on PitNET cells, opening avenues to explore their potential as drugs to treat these pathologies.This work has been funded by the following grants: Junta de Andalucía (CTS-1406 to R.M.L., BIO-0139 to J.P.C.), Ministerio de Ciencia, Innovación y Universidades (BFU2016-80360-R to J.P.C., FJCI-2016-30825 to A.I.C.), and Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, “Investing in Your Future”: PI16/00264 to R.M.L., CP15/00156 to M.D.G., and CIBERobn). CIBER is an initiative of Instituto de Salud Carlos III.Peer reviewe

Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease

[Context] Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse.[Objectives] This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas.[Methods] A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years’ follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery.[Results] Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P < .001).[Conclusion] This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas.This work was supported by the Junta de Andalucía (Nos. P20_00442, PEER-0048-2020, A-0006-2017, A-0055-2018, C-0015-2014, RC-0006-2018; postdoctoral grant DOC_01584, and BIO-0139); Ministry of Science and Innovation (Nos. PID2019-105564RB-I00 and PID2019-105201RB-I00); Instituto de Salud Carlos III, cofunded by the European Union (ERDF/ESF, “Investing in your future”; Nos. PI13/02043; PI16/00175, PI21/01012, and Sara Borrell programme CD19/00255); Spanish Ministry of Universities (predoctoral contract FPU16-05059); a GETNE2019 research grant; and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.Peer reviewe