RESUMEN
Accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) are implicated in the progression of pathologies associated with aging, chronic inflammation, diabetes, and cellular stress. RAGE activation is also implicated in cardiovascular complications of type 2 diabetes, such as nephropathy, retinopathy, accelerated vascular diseases, and cardiomyopathy. Studies investigating the effects of AGE/RAGE axis activation on skeletal muscle oxidative stress and metabolism are more limited. We tested whether a high-fat diet (HFD) would alter circulating AGE concentration, skeletal muscle AGE accumulation, and oxidative stress in wild-type and RAGE-deficient mice. The physiological significance of AGE/RAGE axis activation in HFD-fed mice was evaluated in terms of exercise tolerance and mitochondrial respiratory chain complex activity. HFD elicited adiposity, abnormal fat distribution, and oral glucose intolerance. HFD also induced accumulation of Nε-carboxymethyl-l-lysine, increased protein carbonyl levels, and impaired respiratory chain complex activity in soleus muscle. Ablation of RAGE had no effects on weight gain and oral glucose tolerance in HFD-fed mice. Peak aerobic capacity and mitochondrial cytochrome-c oxidase activity were restored in HFD-fed RAGE-/- mice. We concluded that RAGE signaling plays an important role in skeletal muscle homeostasis of mice under metabolic stress. Novelty HFD in mice induces accumulation of AGEs, oxidative stress, and mitochondrial dysfunction in the soleus muscle. RAGE, the multi-ligand receptor for AGEs, modulates oxidative stress and mitochondrial electron transport chain function in the soleus muscle of HFD-fed mice.
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Dieta Alta en Grasa , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Estrés Oxidativo/fisiología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
To date, there is no evidence regarding the best biological marker to predict erectile dysfunction (ED) in men aged >55 years with type 2 diabetes. This prospective study included data from men aged >55 years with type 2 diabetes. ED was assessed by the International Index of Erectile Function 15-item survey. Total testosterone (TT) levels and bioavailable testosterone were measured; the free testosterone index was calculated. Data from 155 men (aged 64 ± 7 years) were explored. The prevalence of ED and testosterone deficiency was 78.7% and 34.8%, respectively. After univariate analysis, TT and bioavailable testosterone were associated with ED (P = 0.01). After multivariate analysis, and adjustment for age, body mass index, tobacco, alcohol, duration of diabetes, TT, bioavailable testosterone, vitamin D and high-sensitivity C-reactive protein, we found that only high-sensitivity C-reactive protein was significantly predictive of ED. TT could predict ED, but it lacks specificity. We found a potential role of high-sensitivity C-reactive protein as a predictive marker of ED in this targeted population.
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Biomarcadores/análisis , Índice de Masa Corporal , Disfunción Eréctil/diagnóstico , Obesidad/fisiopatología , Testosterona/sangre , Estudios de Casos y Controles , Estudios Transversales , Disfunción Eréctil/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosAsunto(s)
Diabetes Gestacional , Glucemia , Femenino , Edad Gestacional , Prueba de Tolerancia a la Glucosa , Humanos , EmbarazoRESUMEN
Graves' disease is the most frequent cause of hyperthyroidism. Many questions remain about the choice of diagnostic evaluations and treatment strategy according to clinical context (age, gender, pregnancy, etc.) and about the best management of the main extrathyroidal complication that is Graves orbitopathy. The exact pathogenic mechanisms are not fully clear. They associate genetic factors, interactions between endogenous and environmental factors, and immune system dysregulation. Graves' orbitopathy is one of the consequences of this partial understanding. Iatrogenic Graves' disease induced by the new targeted therapies are described and could help to better understand the molecular pathways involved in the disease and to develop new therapeutic approaches.
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Ambiente , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/epidemiología , Enfermedad de Graves/etiología , Edad de Inicio , Susceptibilidad a Enfermedades/complicaciones , Susceptibilidad a Enfermedades/epidemiología , Susceptibilidad a Enfermedades/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Humanos , Enfermedad Iatrogénica/epidemiología , Fenómenos del Sistema Inmunológico/fisiología , Infecciones/complicaciones , Infecciones/epidemiologíaRESUMEN
OBJECTIVES: Apolipoprotein E gene (APOE) polymorphism is associated with the lipid profile and cardio-vascular disease. However, these relationships vary between ethnic groups. We evaluated, for the first time in an Afro-Caribbean population, the distribution of APOE polymorphisms and their associations with coronary artery disease (CAD), the lipid profile and other cardio-metabolic risk factors. METHODS: We studied 712 Afro-Caribbean subjects including 220 with documented CAD and 492 healthy subjects. TaqMan assays were performed to genotype rs7412 and rs429358, the two variants that determine the APOE alleles ε2, ε3 and ε4. The association between APOE genotype and the lipid profile was analysed by comparing ε2 carriers, ε3 homozygotes and ε4 carriers. RESULTS: The frequencies of ε2, ε3 and ε4 in the overall sample were 8%, 70% and 22%, respectively. CAD was not associated with APOE polymorphism. The total cholesterol level was higher in ε4 carriers compared with ε2 carriers: 5.07 vs 4.59 mmol/L (P = 0.016). The LDL-cholesterol level was lower in APOE ε2 carriers compared with ε3 homozygotes and ε4 carriers: 2.65 vs 3.03 and 3.17 mmol/L, respectively (p = 0.002). The total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios were similar in the three allelic groups. APOE polymorphism was not associated with diabetes, hypertension, waist circumference or body mass index. CONCLUSIONS: Our results indicate that APOE gene polymorphism is associated with the lipid profile but not with CAD in Afro-Caribbean people. This lack of association with CAD may be explained by the low atherogenic profile observed in ε4 carriers, which may warrant further investigation.
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Apolipoproteínas E/genética , Población Negra/genética , Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Polimorfismo Genético , Análisis de Varianza , Índice de Masa Corporal , Región del Caribe/etnología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/etnología , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/etnología , Complicaciones de la Diabetes/genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/etnología , Hipertensión/genética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Isoformas de ProteínasRESUMEN
BACKGROUND: The deposit of advanced glycation end-products is involved in diabetic complications. It can be evaluated by measuring the skin autofluorescence (sAF). We searched whether sAF progressed over 4 years in type 1 diabetes and analysed its relationship with the development of nephropathy. METHODS: Two measurements of skin autofluorescence (sAF) were completed on 154 patients during years 2009 and 2013. Baseline factors associated with the progression of sAF were analysed by multivariate regression analysis. The relations among sAF progression, microalbuminuria, and impaired estimated glomerular filtration rate (eGFR) were analysed by logistic regression analysis. RESULTS: The patients were 51 ± 16 years old, with duration of diabetes of 23 ± 13 years, HbA1c: 7.7 ± 1.0%, 20.7% were treated by continuous subcutaneous insulin infusion (CSII). The sAF progressed by +18.1% over 4 years. Two interacting (P = .04) variables were associated with the later progression of sAF: mildly impaired eGFR and treatment by CSII. The patients with mildly impaired eGFR had the highest progression of sAF (+11.5% P = .01). Continuous subcutaneous insulin infusion was associated with a reduced progression of sAF in patients without kidney impairment (ß = -7.2%, P = .01). A +10% progression of sAF during the follow-up was associated with more microalbuminuria: OR = 1.45, P = .02, and more mildly impaired eGFR (<90 mL/min/1.73 m2 ): OR 1.22, P = .03 at 4 years of follow-up. CONCLUSIONS: The skin autofluorescence of advanced glycation end-products progresses in patients with type 1 diabetes, more if they have diabetic nephropathy, less if they are treated by continuous subcutaneous insulin infusion. This progression is associated with the development of nephropathy.
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Diabetes Mellitus Tipo 1/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Piel/metabolismo , Adulto , Anciano , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Progresión de la Enfermedad , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Imagen Óptica , Factores de RiesgoRESUMEN
AIM: We aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D], insulin resistance and leptin-to-adiponectin (L/A) ratio in Guadeloupean children and adolescents and to analyse the changes in 25(OH)D levels after a 1-year lifestyle intervention program. METHODS: 25(OH)D concentrations were measured via a chemiluminescence assay. Cardiometabolic risk factors, homoeostasis model assessment of insulin resistance (HOMA-IR), and adipokines were measured. The lifestyle intervention included dietary counselling, regular physical activity. RESULTS: Among 117 girls and boys (11-15 years old, 31.6% obese), 40% had vitamin D deficiency (25(OH)D levels < 20 ng/mL). With linear regression models where 25(OH)D and HOMA-IR acted as independent variables and age, sex, BMI, L/A ratio as covariates, 25(OH)D was significantly associated with HOMA-IR alone (P = 0.036). HOMA-IR was also associated with BMI z-score ≥ 2, L/A ratio and an interaction term BMI z-score ≥ 2*L/A ratio (P < 0.001 for all). After one year, in 78 children/adolescent, mean serum 25(OH)D increased significantly from 21.4 ± 4.9 ng/mL at baseline to 23.2 ± 6.0 after 1 year; P = 0.003 whereas BMI z-score, HOMA-IR and L/A ratio decreased significantly (P = 0.003, P < 0.001 and P = 0.012; respectively). CONCLUSION: The association between 25(OH)D and HOMA-IR, independently of obesity and the high prevalence of vitamin D deficiency should be considered in order to prevent the later incidence of T2DM. A healthy lifestyle including non-sedentary and outdoor activities could be a way for improving vitamin D status.
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BACKGROUND: We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). METHODS: Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. RESULTS: Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31-17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.
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Diabetes Mellitus Tipo 1/metabolismo , Angiopatías Diabéticas/etiología , Nefropatías Diabéticas/etiología , Productos Finales de Glicación Avanzada/metabolismo , Piel/metabolismo , Adulto , Anciano , Albuminuria/diagnóstico , Albuminuria/etiología , Albuminuria/fisiopatología , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Angiopatías Diabéticas/diagnóstico , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/fisiopatología , Modelos Logísticos , Estudios Longitudinales , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Primary adrenal hypercortisolism is mainly due to cortisol-producing adrenocortical adenomas, bilateral micronodular or macronodular disease, and adrenal carcinomas. Important advances in the pathophysiology of primary adrenal hypercortisolism have been made in the last few years, partly through the use of new molecular biology tools. Most adrenal abnormalities leading to increased cortisol production involve somatic or germinal mutations of genes encoding elements of the cyclic AMP/protein kinase A signaling pathway, as shown in adrenal adenomas in 2014. One peculiar condition is primary macronodular adrenal hyperplasia (PMAH), which has given rise to new pathophysiological concepts such as regulation of cortisol secretion by illegitimate ligands through aberrant expression of G protein-coupled transmembrane receptors in adrenal nodules and stimulation of cortisol production by local adrenocorticotropic hormone production through autocrine/paracrine mechanisms. These findings provide a basis for the development of targeted therapies as an alternative to surgery. The recent identification of germinal mutations of ARMC5 in PMAH raises the possibility that this is much more frequently an inherited disease than previously suspected. It also offers the possibility of earlier diagnosis of PMAH by genetic screening and, hopefully, of earlier intervention to prevent the onset of hypercortisolism and its complications. The pathophysiology of Cushing's syndrome associated with a subset of adrenal adenomas, including subclinical cortisol-secreting incidentalomas and adrenal carcinomas, remains to be determined.
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Neoplasias de las Glándulas Suprarrenales/complicaciones , Síndrome de Cushing/etiología , Síndrome de Cushing/genética , HumanosRESUMEN
BACKGROUND: Despite excessive rates of cardiovascular risk factors such as hypertension, diabetes, and obesity, Afro-Caribbeans have lower mortality rates from coronary heart disease (CHD) than do whites. This study evaluated the association of genetic risk markers previously identified in whites and CHD in Afro-Caribbeans. METHODS: We studied 537 Afro-Caribbean individuals (178 CHD cases and 359 controls) who were genotyped for 19 CHD-related single-nucleotide polymorphisms (SNPs). A genetic risk score (GRS) incorporating the 19 SNPs was calculated. These participants were compared with 1360 white individuals from the Second Northwick Park Heart Study. RESULTS: In Afro-Caribbeans, patients with CHD had higher rates of hypertension (78.7% vs 30.1%), hypercholesterolemia (52.8% vs 15.0%), and diabetes (53.9% vs 14.8%) and were more often men (64.0% vs 43.7%) and smokers (27.5% vs 13.4%) compared with non-CHD controls (all P < 0.001). The GRS was higher in Afro-Caribbeans with CHD than in those without CHD (13.90 vs 13.17; P < 0.001) and was significantly associated with CHD after adjustment for cardiovascular risk factors, with an odds ratio of 1.40 (95% confidence interval, 1.09-1.80) per standard deviation change. There were significant differences in allelic distributions between the 2 ethnic groups for 14 of the 19 SNPs. The GRS was substantially lower in Afro-Caribbean controls compared with white controls (13.17 vs 16.59; P < 0.001). CONCLUSIONS: This study demonstrates that a multilocus GRS composed of 19 SNPs associated with CHD in whites is a strong predictor of the disease in Afro-Caribbeans. The differences in CHD occurrence between Afro-Caribbeans and whites might be a result of significant discrepancies in common gene variant distribution.
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Población Negra/genética , Enfermedad Coronaria/etnología , Enfermedad Coronaria/genética , Polimorfismo de Nucleótido Simple , Medición de Riesgo , Estudios de Casos y Controles , Diabetes Mellitus/epidemiología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Guadalupe/etnología , Humanos , Hipercolesterolemia/epidemiología , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Fumar/epidemiología , Población Blanca/genéticaRESUMEN
CONTEXT: Somatostatin receptor scintigraphy with (111)In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with (68)Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. PURPOSE: To compare the performances of (68)Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. DESIGN AND SETTING: Single-institution prospective comparative study PATIENTS AND METHODS: Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, (18)F-2-fluoro-deoxy-D-glucose ((18)F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. RESULTS: The sensitivity of (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on (68)Ga-DOTA-TOC PET/CT. (68)Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p < 0.03). False negatives of (68)Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and (18)F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with (68)Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. CONCLUSIONS: Owing to higher diagnostic performance, (68)Ga-DOTA-TOC PET/CT (or alternative (68)Ga-labeled somatostatin analogues) should replace (111)In-pentetreotide in the investigation of MEN1 patients.
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Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/análogos & derivados , Compuestos Organometálicos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Duodeno , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
CONTEXT: Bilateral adrenalectomy is the reference treatment for Cushing's syndrome (CS) related to primary bilateral macronodular adrenal hyperplasia (PBMAH). It is, however, responsible for definitive adrenal insufficiency. OBJECTIVE: The objective of the study was to evaluate the clinical interest of unilateral adrenalectomy (UA) of the larger gland for the treatment of CS related to PBMAH. DESIGN, SETTING, PATIENTS, AND INTERVENTION: This was a retrospective study in four tertiary French centers including all 15 patients with PBMAH and CS who underwent UA of the larger gland between 2001 and 2015. MAIN OUTCOME MEASURES: Urinary free cortisol, plasma cortisol, ACTH, body mass index, blood pressure, plasma glucose, and lipids were registered pre- and postoperatively and on follow-up. Median follow-up was 60 months (interquartile range 39-105), including 8 of 15 patients followed up for at least 5 years. RESULTS: A normal or low urinary free cortisol was obtained in 15 of 15 patients (100%) postoperatively. Six patients (40%) became adrenal insufficient, of whom three of six recovered a quantitatively normal cortisol secretion on follow-up. Decrease of both body mass index and blood pressure were observed at 1 year, and decrease of blood pressure was persistent 5 years postoperatively. Diabetes was cured in four of six patients. Two patients experienced a recurrence of hypercortisolism, and one was treated with mitotane, whereas the other underwent a second adrenal surgery 9 years after initial UA. CONCLUSION: UA induced remission of hypercortisolism in all patients, with sustained significant clinical improvement. The rates of both definitive adrenal insufficiency and 5-year recurrence were low. UA appears an interesting alternative to bilateral adrenalectomy as a first-line treatment in PBMAH responsible for overt CS.
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Hiperplasia Suprarrenal Congénita/cirugía , Adrenalectomía/métodos , Síndrome de Cushing/cirugía , Hiperplasia Suprarrenal Congénita/patología , Insuficiencia Suprarrenal/etiología , Insuficiencia Suprarrenal/metabolismo , Adrenalectomía/efectos adversos , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Antineoplásicos Hormonales/uso terapéutico , Glucemia/análisis , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Síndrome de Cushing/tratamiento farmacológico , Síndrome de Cushing/etiología , Síndrome de Cushing/patología , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Lípidos/sangre , Masculino , Persona de Mediana Edad , Mitotano/uso terapéutico , Complicaciones Posoperatorias/metabolismo , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND: We assessed the prognostic value of protein-energy wasting (PEW) on mortality in Afro-Caribbean MHD patients and analysed how diabetes, cardiovascular disease (CVD) and inflammation modified the predictive power of a severe wasting state. METHOD: A 3-year prospective study was conducted in 216 patients from December 2011. We used four criteria from the nomenclature for PEW proposed by the International Society of Renal Nutrition and Metabolism in 2008: serum albumin 38 g/L, body mass index (BMI) ≤23 kg/m(2), serum creatinine ≤818 µmol/L and protein intake assessed by nPCR ≤0.8 g/kg/day. PEW status was categorized according the number of criteria. Cox regression analyses were used. RESULTS: Forty deaths (18.5 %) occurred, 97.5 % with a CV cause. Deaths were distributed as follows: 7.4 % in normal nutritional status, 13.2 % in slight wasting (1 PEW criterion), 28 % in moderate wasting (2 criteria) and 50 % in severe wasting (3-4 criteria). Among the PEW markers, low serum albumin (HR 3.18; P = 0.001) and low BMI (HR 1.97; P = 0.034) were the most significant predictors of death. Among the PEW status categories, moderate wasting (HR 3.43; P = 0.021) and severe wasting (HR 6.59; P = 0.001) were significant predictors of death. Diabetes, CVD, and inflammation were all additives in predicting death in association with severe wasting with a strongest HR (7.76; P < 0.001) for diabetic patients. CONCLUSIONS: The nomenclature for PEW predicts mortality in our Afro-Caribbean MHD patients and help to identify patients at risk of severe wasting to provide adequate nutritional support.
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Primary hyperparathyroidism (PHPT) and vitamin D (VD) deficiency are frequent conditions due to the widespread application of assays for calcium and VD. PHPT presentation is dominated by diversity in its expression and the current predominance of asymptomatic forms. VD, which plays a major role in calcium and phosphate homeostasis, is also involved in many physiological processes in this disease, such as lipid and glucose metabolism, and in the signalling pathways and functioning of many cell types. The bone and cardiometabolic complications described in PHPT are exacerbated by vitamin D deficiency, the prevalence of which varies according to many parameters (environment, skin pigmentation, associated chronic diseases, liver and kidney function, assay kit used, etc.). In response to this observation, experts in field from medical societies validated the indication for systematic assay of VD occurring with PHPT and the need for replacement in case of deficiency. Several epidemiological studies have confirmed that replacement with natural vitamin D is well tolerated and safe in subjects with PHPT and VD deficiency. This supplementation reduces hyperparathormonemia, does not have symptomatic effects on calciuria, and especially improves the bone and functional condition of patients.
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Hiperparatiroidismo Primario/etiología , Deficiencia de Vitamina D/complicaciones , Enfermedades Óseas/etiología , Humanos , Hiperparatiroidismo Primario/epidemiología , Hiperparatiroidismo Primario/genética , Hiperparatiroidismo Primario/fisiopatología , Vitamina D/metabolismo , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/fisiopatología , Vitaminas/uso terapéuticoRESUMEN
BACKGROUND: Lymph node metastases are relatively common in thyroid carcinoma, but retropharyngeal nodes (RPN) are rare. Management may be surgical or non-surgical, according to the context of the disease. METHODS: Systematic review of cases reported in the literature and report of 5 cases. RESULTS: Most case series report surgical management, via a cervical or transoral approach. RPN was the specific object of 26 case series, with a total of 85 patients, with surgery performed in 22/26 studies. Our 5 cases illustrated various strategies in the multidisciplinary management, with surgery for three patients (also with (131)I in one case), targeted therapy for one patient with concurrent distant metastases, and watch and wait for one elderly patient. CONCLUSIONS: Management of RPN is not always surgical. Discussion of options in a multidisciplinary tumor board setting may optimize care.
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Carcinoma/secundario , Carcinoma/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Imagen Multimodal , Cuello , Faringe , Tomografía de Emisión de Positrones , Tiroidectomía , Tomografía Computarizada por Rayos X , Espera VigilanteAsunto(s)
Antitiroideos/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad de Graves/tratamiento farmacológico , Hepatitis Autoinmune/diagnóstico , Metimazol/uso terapéutico , Adulto , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/complicaciones , Hepatitis Autoinmune/complicaciones , HumanosRESUMEN
AIMS/INTRODUCTION: The aim of the present study was to examine the associations of rs2241766 (+45T>G), rs1501299 (+276G>T), rs17300539 (-11391G>A) and rs182052 (-10069G>A) in the adiponectin (Ad) gene with adiponectin concentrations, and concomitantly the association of these variants with cardiometabolic risk in type 2 diabetic patients of African ancestry. MATERIALS AND METHODS: A cross-sectional study of 200 patients was carried out. Concentrations of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms were measured. The four polymorphisms were genotyped. RESULTS: Decreased values were noted for total Ad in overweight, dyslipidemia and coronary artery disease (CAD), for HMW in overweight and dyslipidemia, for MMW in CAD, for LMW in dyslipidemia and CAD, for the percentage HMW/total in overweight, and for MMW:HMW ratio in patients without hypertriglyceridemic waist (HTGW). Significant associations were noted between total Ad, HMW, and HMW/total Ad and rs182052 under a dominant model (P = 0.04, P = 0.03 and P = 0.04, respectively), and between MMW and rs17300539 (P = 0.006). No significant difference in adiponectin concentrations was noted according to rs2241766 and rs1501299 genotypes. Patients carrying the rs2241766 G allele (TG+GG) had an increased risk of HTGW (odds ratio [OR] 3.1; P = 0.04) and of CAD (OR 3.3; P = 0.01). The odds of having low total adiponectin concentrations (<25th percentile: 3.49 ng/mL) for carrying the rs182052A allele (AA+GA) was: OR 0.40; P = 0.009. The single-nucleotide polymorphism associated with adiponectin levels was not concomitantly associated with cardiometabolic risk factors. CONCLUSIONS: Adiponectin concentrations and ADIPOQ variants are implicated in the pathophysiological process leading to cardiovascular diseases, but the genetic effects seem to be independent of adiponectin concentrations in our Afro-Caribbean diabetic patients.
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BACKGROUND: Traditional risk factors are strong predictors of the incidence of coronary artery disease (CAD), but their association with disease severity remains controversial and could differ across ethnic groups. AIMS: In this study, we assessed the prevalence of cardiovascular risk factors (CRFs) in Afro-Caribbean patients with documented CAD, and sought to identify which of these factors are related to disease severity. METHODS: We retrospectively studied 420 consecutive patients with CAD. Disease severity was determined from the results of invasive coronary angiography, based on the presence or absence of multiple (two or three) diseased vessels and the myocardial jeopardy (MJ) score. RESULTS: In the studied population (mean age 64.7 ± 12.4 years), hypertension, diabetes and dyslipidaemia were the most frequent modifiable CRFs, present in 75.9, 47.8 and 37.8% of patients, respectively. Multiple logistic regression analysis showed that diabetes, male sex and personal cardiovascular history significantly increased the risk of multivessel CAD: odds ratios (ORs) of 1.53 (1.01-2.33; P=0.048), 1.61 (1.02-2.55; P=0.043) and 1.68 (1.11-2.56; P=0.015), respectively. Obesity was an independent negative predictor, with an OR of 0.48 (0.29-0.79; P=0.004). Other traditional CRFs (hypertension, dyslipidaemia, smoking, age and family history of vascular disease) were not associated with CAD severity. For high-risk lesions (MJ score ≥8), both diabetes and hypertension were independent predictors of disease severity, whereas obesity was no longer a protective factor. CONCLUSION: Diabetes emerged as the strongest modifiable risk factor predictor of multivessel disease in Afro-Caribbean patients, whereas obesity was an independent protective factor. The underlying mechanisms of these associations should be relevant to disease prevention.
Asunto(s)
Enfermedad de la Arteria Coronaria/etnología , Anciano , Población Negra , Distribución de Chi-Cuadrado , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico , Diabetes Mellitus/etnología , Guadalupe/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/etnología , Oportunidad Relativa , Prevalencia , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Our aim was to assess the associations between vitamin D (vitD) status, metabolic profile and polymorphisms in genes involved in the transport (Group-Component: GC) and the hydroxylation (NAD synthetase 1: NADSYN1) of 25 hydroxyvitamin D (25(OH)D) in non-diabetic individuals. METHODS: We conducted a cross-sectional study with 323 individuals recruited from the Health Center of Guadeloupe, France. The rs2282679 T > G and rs2298849 T > C in GC and rs12785878 G > T in NADSYN1 were genotyped. RESULTS: Mean age was 46(range 18-86) years. 57% of participants had vitD insufficiency, 8% had vitD deficiency, 61% were overweight and 58% had dyslipidemia. A higher frequency of overweight was noted in women carrying rs2298849T allele v CC carriers (71% v 50%; P = 0.035). The rs2282679G allele was associated with increased risks of vitD deficiency and vitD insufficiency (OR =3.53, P = 0.008, OR = 2.34, P = 0.02 respectively). The rs2298849 TT genotype was associated with vitD deficiency and overweight (OR =3.4, P = 0.004 and OR = 1.76, P = 0.04 respectively) and the rs12785878 GG genotype with vitD insufficiency and dyslipidemia (OR = 1.80, P = 0.01 and OR = 1.72, P = 0.03 respectively). Based on the number of risk alleles for rs2282679 and rs12785878 combined, a genotype score of 3 (vs. 0-1) was associated with a 5.5 ng/mL average reduction in serum 25(OH)D levels (P = 0.001). CONCLUSIONS: The GC and NADSYN1 genes are associated with the vitamin D status and might contribute to dyslipidemia and overweight independently of 25(OH)D levels.
RESUMEN
The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.