GALIPDIA study: Reaching lipid targets in a population with type 2 diabetes (T2DM) from the Northwest of Spain.

AIM: To assess the degree of compliance with the European ESC/EAS 2016 and 2019 dyslipidaemia guidelines in patients with type 2 diabetes mellitus (T2DM). METHODS: Multicentre retrospective cross-sectional study, conducted in 380 adults with T2DM and dyslipidaemia in 7 Spanish health areas. INCLUSION CRITERIA: minimum follow-up of one year in Endocrinology Units, at least one visit in 2020 and a lipid profile measurement in the last 3 months. EXCLUSION CRITERIA: familial hypercholesterolaemia, recent hospitalisation, active oncological pathology and dialysis. RESULTS: According to the 2016 and 2019 guidelines the majority of patients were classified as being at very high cardiovascular risk (86.8% vs. 72.1%, respectively). LDL-c compliance was adequate in 62.1% of patients according to the 2016 guidelines and 39.7% according to the 2019 guidelines (p<0.001). Clinical conditions such as history of cardiovascular disease and therapy-related aspects (use of statins, especially high-potency statins, combination therapies and good adherence) were significantly associated with greater achievement of lipid targets. CONCLUSION: There is a discrepancy between dyslipidaemia guideline recommendations and the reality of lipid control in patients with T2DM, despite most of these patients being at very high cardiovascular risk. Strategies to optimise lipid-lowering treatments need to be implemented.

Pseudohypoxia in paraganglioma and pheochromocytoma is associated with an immunosuppressive phenotype.

Metastatic pheochromocytoma and paraganglioma (PPGL) have poor prognosis and limited therapeutic options. The recent advent of immunotherapies showing remarkable clinical efficacies against various cancer types offers the possibility of novel opportunities also for metastatic PPGL. Most PPGLs are pathogenically linked to inactivating mutations in genes encoding different succinate dehydrogenase (SDH) subunits. This causes activation of the hypoxia-inducible factor 2 (HIF2)-mediated transcriptional program in the absence of decreased intratumoral oxygen levels, a phenomenon known as pseudohypoxia. Genuine hypoxia in a tumor creates an immunosuppressive tumor microenvironment. However, the impact of pseudohypoxia in the immune landscape of tumors remains largely unexplored. In this study, tumoral expression of programmed death-ligand 1 (PD-L1) and HIF2α and tumor infiltration of CD8 T lymphocytes (CTLs) were examined in PPGL specimens from 102 patients. We assessed associations between PD-L1, CTL infiltration, HIF2α expression, and the mutational status of SDH genes. Our results show that high PD-L1 expression levels in tumor cells and CTL tumor infiltration were more frequent in metastatic than nonmetastatic PPGL. However, this phenotype was negatively associated with SDH mutations and high HIF2α protein expression. These data were validated by analysis of mRNA levels of genes expressing PD-L1, CD8, and HIF2α in PPGL included in The Cancer Genome Atlas database. Further, PD-L1 and CD8 expression was lower in norepinephrine than epinephrine-secreting PPGL. This in silico analysis also revealed the low PD-L1 or CD8 expression levels in tumors with inactivating mutations in VHL or activating mutations in the HIF2α-coding gene, EPAS1, which, together with SDH-mutated tumors, comprise the pseudohypoxic molecular subtype of PPGL. These findings suggest that pseudohypoxic tumor cells induce extrinsic signaling toward the immune cells promoting the development of an immunosuppressive environment. It also provides compelling support to explore the differential response of metastatic PPGL to immune checkpoint inhibitors. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Biological implications of selenium in adolescent rats exposed to binge drinking: Oxidative, immunologic and apoptotic balance.

Alcohol intermittent binge drinking (BD) during adolescence decreases the levels of selenium (Se), a trace element that plays a key biological role against oxidative damage in hepatocytes through different selenoproteins such as the antioxidant enzymes glutathione peroxidases (GPx1 and Gpx4) and selenoprotein P (SelP). In this context, it has been found that GPx4 has an essential antioxidant role in mitochondria modulating the apoptosis and NF-kB activation (a factor intimately related to apoptosis and immune function). To further investigate the effectiveness of selenium supplementation in oxidative balance, inflammation and apoptosis, the present study examined the protective effects of 0.4ppm of dietary selenite administrated to adolescent rats exposed to BD. BD consumption depleted Se deposits in all the tissues studied. In liver, GPx1 activity and expression were decreased leading to protein and lipid hepatic oxidation. Moreover GPx4 and NF-kB expression were also decreased in liver, coinciding with an increase in caspase-3 expression. This hepatic profile caused general liver damage as shown the increased serum transaminases ratio AST/ALT. Proinflammatory serum citokines and chemocines were decreased. Se supplementation therapy used restored all these values, even AST levels. These findings suggest for first time that Se supplementation is a good strategy against BD liver damage during adolescence, since it increases GPx1 and GPx4 expression and avoids NF-kB downregulation and caspase-3 upregulation, leading to a better oxidative, inflammatory and apoptotic liver profile. The therapy proposed could be considered to have a great biological efficacy and to be suitable for BD exposed teenagers in order to avoid future hepatic complications.

[Anthropometric parameters in evaluating malnutrition in oncological patients; utility of body mass index and percentage of weight loss]. / Parámetros antropométricos en la evaluación de la malnutrición en pacientes oncológicos hospitalizados; utilidad del índice de masa corporal y del porcentaje de pérdida de peso.

OBJECTIVE: To compare the BMI and the percentage of weight loss as markers for malnutrition in hospitalized cancer patients considering the Patient-Generated Global Subjective Assessment (PG-GSA) as the gold standard. METHOD: Cross-sectional descriptive study in patients admitted to the Medical Oncology Department of the Hospital Xeral de Vigo, from May to September of 2011. RESULTS: 28 patients (15 males). Mean age 63.46 years ± 11.05. Mean BMI 23.75 kg/m² ± 3.62. Mean percentage of weight loss 8.53% ± 6.20. In group A (well nourished) the percentage of weight loss was 1.07 ± 1.85, in group B (moderately malnourished) 7.90 ± 1.73, and in group C (severely malnourished) 10.91 ± 6.91 (p = 0.034). The BMI showed no statistically significant differences. CONCLUSIONS: The BMI is not a proper parameter todetect malnutrition, by contrast with the percentage of weight loss that did show a direct association with the degree of hyponutrition.

Objetivo: Comparar el IMC y el porcentaje de pérdida de peso como marcadores de malnutrición en el paciente oncológico hospitalizado tomando como referencia la Valoración Subjetiva Global Generada por el Paciente (VSG-GP). Método: Estudio descriptivo transversal en pacientes ingresados en Oncología Médica del Hospital Xeral de Vigo de mayo a septiembre de 2011. Resultados: 28 pacientes (15 varones). Edad media 63,46 años ± 11,05. IMC medio 23,75 kg/m2 ± 3,62. Porcentaje medio de pérdida de peso 8,53% ± 6,20. En el grupo A (bien nutridos) el porcentaje de pérdida de peso fue de 1,07 ± 1,85, en el B (moderadamente desnutridos) de 7,90 ± 1,73 y en el C (severamente desnutridos) 10,91 ± 6,91 (p = 0,034). El IMC no obtuvo diferencias estadísticamente significativas. Conclusiones: El IMC no es un parámetro adecuado para detectar malnutrición a diferencia del porcentaje de pérdida de peso que sí mostró una asociación directa con el grado de desnutrición.

Factors influencing the outcome of patients with incidental papillary thyroid microcarcinoma.

Objective. To analyze some factors that could influence the outcome of patients with PTMC. Material and Methods. This is a longitudinal observational study. All patients diagnosed and treated for papillary thyroid microcarcinoma at the University Hospital of Vigo, between January 1994 and December 2003, were included in the present study. Demographic characteristics, tumour characteristics, TNM stage, rate of recurrence, and treatment with (131)I were the study variables. Results. Ninety-one patients (75 females) with an average age of 47.7 ± 13.4 years, range 19-81, were studied. Initial tumour staging was T1 in 90 patients and T4a in 1 case. Initial lymph node involvement was present in 4 cases (4.4%). We only found one case with distant metastases at diagnosis. Postsurgical evaluation of thyroid specimens revealed that 28 (30.7%) tumours were multifocal. The average size of the tumour was 0.44 ± 0.25 cm, range 0.1-1. Univariate analysis reveals a statistically significant association between tumour multifocality and postsurgical (131)I therapy with the recurrence rate. In the multivariate analysis only multifocality (P = 0.037, HR 5.7) was a significant risk factor for the recurrence rate. Conclusions. Our results indicate that tumour multifocality is an independent predictor of relapse but neither the tumour size nor postsurgical (131)I therapy.

[Phenotype of the C634Y mutation in the RET proto-oncogene in MEN2A: report of a family]. / Fenotipo de la mutación C634Y del protooncogén RET en el MEN2A: a propósito de una familia.

BACKGROUND AND OBJECTIVES: Genetic testing of RET proto-oncogen allows an early diagnosis of Multiple Endocrine Neoplasia syndrome type 2 and establish a correlation between genotype and clinical manifestations. The purpose of this study was to demonstrate the benefits of an early diagnosis with genetic testing followed by prompt surgery on the cure of MTC versus a later diagnosis with serum calcitonin. PATIENTS AND METHOD: Retrospective descriptive study of 8 members of a MEN 2A family by C634Y mutation. We performed serum calcitonin screening until 1999 and subsequently RET genetic testing was obtained. Carriers underwent total thyroidectomy and periodic determination of calcitonin, urinary metanephrines, calcium, phosphorus and neck and abdominal imaging techniques. RESULTS: Five patients were diagnosed by calcitonin familial screening and all of them have high calcitonin by now. Three patients were diagnosed by genetic testing (an adult and two children) and they are free of disease. Calcitonin was closely monitored in children and they underwent surgery when it started to raise, at 6 and 10 years old respectively, finding nodular C-cell hyperplasia in both. Of 8 carriers 3 developed pheochromocytomas, bilateral and asynchronous, one-half had normal urinary metanephrines and two of them were simultaneous with MTC. No patient had biochemical data suggesting hyperparathyroidism although in one patient multiple parathyroid adenomas were found at thyroidectomy. CONCLUSIONS: RET genetic analysis has achieved an early diagnosis and treatment with no development of MTC in our patients, adjusting the time and type of surgery and allowing a genotype-phenotype correlation. It demonstrates how a genetic alteration is associated with a pathology that we can prevent and manage improving the prognosis of our patients.