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1.
Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study.
García de Lucas, MD, Caballero, I, Fernández-García, JC, Domínguez-Rodríguez, M, Moreno-Moreno, P, Jiménez-Millán, A, Botana-López, M, Avilés, B, Merino-Torres, JF, Soto, A, et al
Frontiers in endocrinology. 2023;:1240279
Abstract
OBJECTIVES Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined. METHOD This is an observational, ambispective, multicenter, nationwide, real-world study designed to compare safety/efficacy of OW s.c. 1 mg semaglutide in T2D patients with or without CKD. The influence of CKD severity was also addressed. Patients were followed up for 12 months. Primary end-points were glycosylated hemoglobin (HbA1c), weight, and renal outcomes. Secondary end-points included insulin resistance, atherogenic and hepatic steatosis indexes, and changes in antihyperglycemic medications. RESULTS A total of 296 and 190 T2D patients without or with CKD, respectively, were recruited. Baseline CKD risk was moderate, high, or very high in 82, 53, and 45 patients, respectively. Treatment reduced HbA1c by 0.90%-1.20%. Relevant differences were seen neither between non-CKD and CKD patients nor among CKD subgroups. Notable weight losses were achieved in both non-CKD and CKD patients. The median reduction was higher in the former at 6 months (5.90 kg vs. 4.50 kg, P = 0.008) and at end of study (6.90 kg vs. 5.00 kg, P = 0.087). A trend toward slightly lower weight losses as CKD severity increased was observed. CKD markers improved across all CKD subgroups. Relevant differences were not observed for other variables, either between non-CKD and CKD patients, or among CKD subgroups. Safety concerns were not reported. CONCLUSION The safety/efficacy of OW s.c. semaglutide to improve glycemic control and weight in T2D patients with CKD is not notably lower than that in T2D patients without renal failure. CKD severity barely influences treatment response. OW s.c. semaglutide can be useful to manage T2D patients with CKD in daily clinical practice.
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Impact of Diabetes Mellitus in Patients with Pancreatic Neuro-Endocrine Tumors: Causes, Consequences, and Future Perspectives.
Hernandez-Rienda, L, Del Olmo-García, MI, Merino-Torres, JF
Metabolites. 2022;(11)
Abstract
Diabetes mellitus (DM) and pancreatic neuroendocrine tumors (pNETs) are two entities closely linked together. DM has been described as a risk factor for the development of pNETs and for the aggressiveness of the disease. On the other hand, DM due to pNETs is frequently undiagnosed or misclassified as type 2 DM when it is due to type 3 DM. In addition, metformin, a commonly prescribed drug for type 2 DM, has an antiproliferative property and is gaining increasing attention as an antitumor agent. This review article presents the findings published in the last few years on pNETs and DMs. Emphasis will be placed on DM as a risk factor, pNET as a risk factor for the development of type 3 DM, the management of type 3 DM on pNET, and DM as a prognostic factor in patients with pNET, as well as the future clinical implications of DM in these patients. The coexistence of DM and pNET is extensively presented. It is important to perform future clinical trials, which are necessary to establish the role of metformin on pNET disease. Increasing awareness among professionals managing pNET on the importance of a correct DM diagnosis and management of the disease must be a priority due to the implications on mortality and comorbidities it may have in these patients.
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The Potential Roles of Extracellular Vesicles as Biomarkers for Parkinson's Disease: A Systematic Review.
Valencia, J, Ferreira, M, Merino-Torres, JF, Marcilla, A, Soriano, JM
International journal of molecular sciences. 2022;(19)
Abstract
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.
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Response to targeted radionuclide therapy with [131I]MIBG AND [177Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review.
Prado-Wohlwend, S, Del Olmo-García, MI, Bello-Arques, P, Merino-Torres, JF
Frontiers in endocrinology. 2022;:957172
Abstract
PURPOSE Targeted radionuclide therapy (TRT) with [131I]MIBG and [177Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [131I]MIBG and [177Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location. METHODS This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student's t distribution. RESULTS In linear regression models, [131I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [131I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample. CONCLUSION Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [131I]MIBG and PRRT-Lu.
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[177Lu]Lu-DOTA-TATE and [131I]MIBG Phenotypic Imaging-Based Therapy in Metastatic/Inoperable Pheochromocytomas and Paragangliomas: Comparative Results in a Single Center.
Prado-Wohlwend, S, Del Olmo-García, MI, Bello-Arques, P, Merino-Torres, JF
Frontiers in endocrinology. 2022;:778322
Abstract
PURPOSE The aim of the study is to assess phenotypic imaging patterns and the response to treatment with [177Lu]Lu-DOTA-TATE and/or [131I]MIBG in paragangliomas (PGLs) and pheochromocytomas (PHEOs), globally and according to the primary location. METHODS This is a 17-patient retrospective observational study, with 9 cases treated with [177Lu]Lu-DOTA-TATE and 8 with [131I]MIBG (37 total treatments). Functional imaging scans and treatment responses were studied in order to choose the best therapeutic option and to define the progression-free survival (PFS) and disease control rate (DCR) according to treatment modality and primary location. RESULTS All patients were studied with phenotypic nuclear medicine images. Twelve of 17 patients were tested with both [123I]MIBG and somatostatin receptor images, and 6/12 showed appropriate expression of both targets to treatment in the phenotypic images. The rest of the patients were tested with one of the image modalities or only showed suitable uptake of a single radiotracer and were treated with the corresponding therapeutic option. [177Lu]Lu-DOTA-TATE PFS was 29 months with a DCR of 88.8%. [131I]MIBG PFS was 18.5 months with a 62.5% DCR. According to the primary location, the best PFS was in PHEOs treated with [177Lu]Lu-DOTA-TATE. Although the series are small due to the low disease prevalence and do not allow to yield statistically significant differences, this first study comparing [177Lu]Lu-DOTA-TATE and [131I]MIBG displays a trend to an overall longer PFS with [177Lu]Lu-DOTA-TATE, especially in the adrenal primary location. When both radionuclide targets are expressed, the patients' comorbidity and treatment effectiveness should be valued together with the intensity uptake in the phenotypic image in order to choose the best therapeutic option. These preliminary retrospective results reinforce the need for a prospective, multicentric trial to be confirmed.
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NUTRARET: Effect of 2-Year Nutraceutical Supplementation on Redox Status and Visual Function of Patients With Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Trial.
Olivares-González, L, Salom, D, González-García, E, Hervás, D, Mejía-Chiqui, N, Melero, M, Velasco, S, Muresan, BT, Campillo, I, Vila-Clérigues, N, et al
Frontiers in nutrition. 2022;:847910
Abstract
Oxidative stress plays a major role in the pathogenesis of retinitis pigmentosa (RP). The main goal of this study was to evaluate the effect of 2-year nutritional intervention with antioxidant nutraceuticals on the visual function of RP patients. Secondly, we assessed how nutritional intervention affected ocular and systemic redox status. We carried out a randomized, double-blind, placebo-controlled study. Thirty-one patients with RP participated in the study. RP patients randomly received either a mixture of nutraceuticals (NUT) containing folic acid, vitamin B6, vitamin A, zinc, copper, selenium, lutein, and zeaxanthin or placebo daily for 2 years. At baseline and after 2-year of the nutritional supplementation, visual function, dietetic-nutritional evaluations, serum concentration of nutraceuticals, plasma and aqueous humor concentration of several markers of redox status and inflammation were assessed. Retinal function and structure were assessed by multifocal electroretinogram (mfERG), spectral domain-optical coherence tomography (SD-OCT) and automated visual field (VF) tests. Nutritional status was estimated with validated questionnaires. Total antioxidant capacity, extracellular superoxide dismutase (SOD3), catalase (CAT), and glutathione peroxidase (GPx) activities, protein carbonyl adducts (CAR) content, thiobarbituric acid reactive substances (TBARS) formation (as indicator of lipid peroxidation), metabolites of the nitric oxide (NOX) and cytokine (interleukin 6 and tumor necrosis factor alpha) concentrations were assessed by biochemical and immunological techniques in aqueous humor or/and blood. Bayesian approach was performed to determine the probability of an effect. Region of practical equivalence (ROPE) was used. At baseline, Bayesian analysis revealed a high probability of an altered ocular redox status and to a lesser extent systemic redox status in RP patients compared to controls. Twenty-five patients (10 in the treated arm and 15 in the placebo arm) completed the nutritional intervention. After 2 years of supplementation, patients who received NUT presented better retinal responses (mfERG responses) compared to patients who received placebo. Besides, patients who received NUT showed better ocular antioxidant response (SOD3 activity) and lower oxidative damage (CAR) than those who received placebo. This study suggested that long-term NUT supplementation could slow down visual impairment and ameliorate ocular oxidative stress.
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Glucagon-Like Peptide-1 Receptor Agonist Use in People Living with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Narrative Review of the Key Evidence with Practical Considerations.
Górriz, JL, Romera, I, Cobo, A, O'Brien, PD, Merino-Torres, JF
Diabetes therapy : research, treatment and education of diabetes and related disorders. 2022;(3):389-421
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Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are incretin-mimetic agents that are effective adjuncts in the treatment of diabetes. This class of medications is also associated with promoting weight loss and a low risk of hypoglycemia, and some have been shown to be associated with a significant reduction of major cardiovascular events. Mounting evidence suggests that GLP-1 RAs have benefits beyond reducing blood glucose that include improving kidney function in people living with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), a common microvascular complication of T2DM. Several large clinical studies, the majority of which are cardiovascular outcome trials, indicate that GLP-1 RA therapy is safe and tolerable for people living with T2DM and compromised renal function, and also suggest that GLP-1 RAs may have renoprotective properties. Although evidence from clinical trials has shown GLP-1 RAs to be safe and efficacious in people living with T2DM and renal impairment, their use is uncommon in this patient population. With continuing developments in the field of GLP-1 RA therapy, it is important for physicians to understand the benefits and practical use of GLP-1 RAs, as well as the clinical evidence, in order to achieve positive patient outcomes. Here, we review evidence on GLP-1 RA use in people living with T2DM and CKD and summarize renal outcomes from clinical studies. We provide practical considerations for GLP-1 RA use to provide an added benefit to guide treatment in this high-risk patient population.
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"Five Keys to Safer Food" and COVID-19.
San Onofre, N, Soler, C, Merino-Torres, JF, Soriano, JM
Nutrients. 2021;(12)
Abstract
On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) and, up to 18:37 a.m. on 9 December 2021, it has produced 268,440,530 cases and 5,299,511 deaths. This disease, in some patients, included pneumonia and shortness of breath, being transmitted through droplets and aerosols. To date, there is no scientific literature to justify transmission directly from foods. In this review, we applied the precautionary principle for the home and the food industry using the known "Five Keys to Safer Food" manual developed by the World Health Organization (WHO) and extended punctually in its core information from five keys, in the light of new COVID-19 evidence, to guarantee a possible food safety tool.
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COVID Obesity: A One-Year Narrative Review.
Ovalle, DLP, Rodrigo-Cano, S, González, A, Soler, C, Catalá-Gregori, AI, Merino-Torres, JF, Soriano, JM
Nutrients. 2021;(6)
Abstract
On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). This study focuses on a narrative review about the illness during the first year of the pandemic in relation to obesity. Databases were used to search studies published up to 8 December 2020. In total, 4430 articles and other scientific literature were found, and 24 articles were included in this one-year narrative review. The mean BMI value of severe COVID-19 patients ranged from 24.5 to 33.4 kg/m2, versus <18.5 to 24.3 kg/m2 for non-severe patients. Articles using the terms obesity or overweight without indicating the BMI value in these patients were common, but this is not useful, as the anthropometric parameters, when not defined by this index, are confusing due to the classification being different in the West compared to among Asian and Korean criteria-based adults. We proposed a new term, called COVID obesity, to define the importance of this anthropometric parameter, among others, in relation with this pandemic.
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Prevention and Management of Hormonal Crisis during Theragnosis with LU-DOTA-TATE in Neuroendocrine Tumors. A Systematic Review and Approach Proposal.
Del Olmo-García, MI, Muros, MA, López-de-la-Torre, M, Agudelo, M, Bello, P, Soriano, JM, Merino-Torres, JF
Journal of clinical medicine. 2020;(7)
Abstract
Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTR) on their cell surface. The first-line pharmacological treatment for inoperable metastatic functioning well-differentiated NETs are somatostatin analogs. On second line, Lu-DOTA-TATE (177Lu-DOTA0 Tyr 3 octreotate) has shown stabilization of the disease and an increase in progression free survival, as well as effectiveness in controlling symptoms and increasing quality of life. The management of functional NETs before and during LU-DOTA-TATE treatment is specially challenging, as several complications such as severe carcinoid and catecholamine crisis have been described. The aim of this review is to establish practical guidance for the management and prevention of the most common hormonal crises during radionuclide treatment with Lu-DOTA-TATE: carcinoid syndrome (CS) and catecholamine hypersecretion, as well as to provide a brief commentary on other infrequent metabolic complications. To establish a practical approach, a systematic review was performed. This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and conducted using MEDLINE (accessed from PubMed), Google Scholar and ClinicalTrials.gov. Literature searches found 449 citations, and finally nine were considered for this systematic review.