Hard-to-Heal Wound Healing: Superiority of Hydrogel EHO-85 (Containing Olea europaea Leaf Extract) vs. a Standard Hydrogel. A Randomized Controlled Trial.

Chronic wounds, especially those that are hard-to-heal, constitute a serious public-health problem. Although progress has been made in the development of wound dressings for healing, there is little high-quality evidence of their efficacy, with no evidence of superiority in the use of one hydrogel over another. To evaluate the superiority of a hydrogel (EHO-85), containing Olea europaea leaf extract (OELE), over a standard hydrogel (SH), the promotion and/or improvement of healing of difficult-to-heal wounds was compared in a prospective, parallel-group multicenter, randomized, observer-blinded, controlled trial ("MACAON"). Non-hospitalized patients with pressure, venous or diabetic foot-ulcers difficult-to-heal were recruited and treated with standard care, and EHO-85 (n = 35) or VariHesive (n = 34) as SH. Wound-area reduction (WAR; percentage) and healing rate (HR; mm2/day) were measured. EHO-85 showed a statistically significant superior effect over VariHesive. At the end of the follow-up period, the relative WAR decreased by 51.6% vs. 18.9% (p < 0.001), with a HR mean of 10.5 ± 5.7 vs. 1.0 ± 7.5 mm2/day (p = 0.036). EHO-85 superiority is probably based on its optimal ability to balance the ulcer bed, by modulating pH and oxidative stress. That complements the wetting and barrier functions, characteristics of conventional hydrogels. These results support the use of EHO-85 dressing, for treatment of hard-to-heal ulcers. Trial Registration AEMPS:PS/CR623/17/CE.

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study.

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.

Non-Specific Inhibition of Dipeptidyl Peptidases 8/9 by Dipeptidyl Peptidase 4 Inhibitors Negatively Affects Mesenchymal Stem Cell Differentiation.

DPP4 may play a relevant role in MSC differentiation into osteoblasts or adipocytes. Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4i), such as sitagliptin and vildagliptin, are used as antidiabetic drugs. However, vildagliptin is not a specific DPP4i and also inhibits DPP8/9, which is involved in energy metabolism and immune regulation. The aim of this study is to evaluate how sitagliptin, vildagliptin or 1G244 (a DPP8/9 specific inhibitor) may influence cell viability, as well as osteogenic and adipogenic differentiation in human mesenchymal stem cells (MSC). Viability, apoptosis, osteoblastogenesis and adipogenesis markers, as well as protein synthesis of ß-catenin, were studied in MSC cultures induced to differentiate into osteoblasts or adipocytes in the presence or absence of sitagliptin, vildagliptin or 1G244. The two tested DPP4i did not affect MSC viability, but 1G244 significantly decreased it in MSC and osteoblast-induced cells. Additionally, 1G244 and vildagliptin inhibited osteogenesis and adipogenesis, unlike sitagliptin. Therefore, inhibition of DPP4 did not affect MSC viability and differentiation, whereas inhibition of DPP8/9 negatively affected MSC. To the best of our knowledge, these results show for the first time that DPP8/9 have an important role in the viability and differentiation of human MSC. This data can be considered for human clinical use of drugs affecting DPP8/9 activity.

Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial.

This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another.

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.

Effectiveness and safety of dapagliflozin in real-life patients: data from the DAPA-RWE Spanish multicentre study.

BACKGROUND: This study aims to evaluate dapagliflozin in patients with type 2 diabetes (T2D) in clinical practice in Spain. METHODS: This is a retrospective study including adults with T2D under stable antidiabetic therapy, with either dapagliflozin or sitagliptin ≥6 months, before inclusion. Data about the effectiveness and safety of dapagliflozin are presented. RESULTS: A total of 594 patients (61.8±9.9 years, 21.7% cardiovascular disease) were included. After 6 months, HbA1c, weight, blood pressure, urine albumin-to-creatinine ratio and uric acid significantly decreased (1.63%, 2.88 kg, 4.82/2.70 mmHg, -17.38 mg/g and -0.30 mg/dL, respectively), whereas glomerular filtration rate and haematocrit significantly increased (3.72 mL/min/1.73 m2 and 1.8%, respectively). No cases of hypoglycaemia, diabetic ketoacidosis, Fournier gangrene, fractures or amputations were reported. CONCLUSION: Thus, dapagliflozin provides a comprehensive cardiometabolic protection in patients with T2D.

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.

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features.

Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in 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.

Hyperlipidemia during gestational diabetes and its relation with maternal and offspring complications.

INTRODUCTION: lipid profile suffers adaptive changes during pregnancy due to estrogen stimulation and insulin resistance. Several relations have been suggested between maternal lipid profile, glucose tolerance, endothelial cell dysfunction and long-term cardiovascular risk; the effects of maternal lipid profile metabolism in fetal growth are also inconclusive. Since a regular evaluation and follow-up of lipid profile during pregnancy has not been established yet, we aimed to evaluate the incidence of dyslipidemia in patients with gestational diabetes (GDM) and analyze some putative relations with pregnancy, offspring complications and maternal metabolic syndrome parameters determined three and twelve months after delivery. PATIENTS AND METHODS: two hundred and fifty patients with GDM were included. Full medical history, offspring characteristics, lipid profile and maternal variables of metabolic syndrome were evaluated during pregnancy and three- and twelve-months after delivery. The incidence of dyslipidemia during pregnancy was determined using two different classifications. RESULTS: lower plasma HDL and hypertriglyceridemia were the most current disorders; prematurity or birth weight were not correlated with dyslipidemia. During pregnancy, the lipid-related parameter that better predicted the risk of offspring macrosomia was triglycerides (TG). High TG three months after delivery were correlated to macrosomia and metabolic syndrome variables before and after pregnancy (three and twelve months). CONCLUSIONS: TG during pregnancy is the parameter that best predicts the risk of macrosomia and is related to increased metabolic risk after delivery. The evaluation of lipid profile and other metabolic variables during pregnancy and after delivery is required to early diagnose cardiovascular risk factors, especially in high risk population.

Hyperlipidemia during gestational diabetes and its relation with maternal and offspring complications / Hiperlipidemia durante la diabetes gestacional, complicaciones maternas y para la descendencia

Introduction: lipid profile suffers adaptive changes during pregnancy due to estrogen stimulation and insulin resistance. Several relations have been suggested between maternal lipid profile, glucose tolerance, endothelial cell dysfunction and long-term cardiovascular risk; the effects of maternal lipid profile metabolism in fetal growth are also inconclusive. Since a regular evaluation and follow-up of lipid profile during pregnancy has not been established yet, we aimed to evaluate the incidence of dyslipidemia in patients with gestational diabetes (GDM) and analyze some putative relations with pregnancy, offspring complications and maternal metabolic syndrome parameters determined three and twelve months after delivery. Patients and methods: two hundred and fifty patients with GDM were included. Full medical history, offspring characteristics, lipid profile and maternal variables of metabolic syndrome were evaluated during pregnancy and three- and twelve-months after delivery. The incidence of dyslipidemia during pregnancy was determined using two different classifications. Results: lower plasma HDL and hypertriglyceridemia were the most current disorders; prematurity or birth weight were not correlated with dyslipidemia. During pregnancy, the lipid-related parameter that better predicted the risk of offspring macrosomia was triglycerides (TG). High TG three months after delivery were correlated to macrosomia and metabolic syndrome variables before and after pregnancy (three and twelve months).Conclusions: TG during pregnancy is the parameter that best predicts the risk of macrosomia and is related to increased metabolic risk after delivery. The evaluation of lipid profile and other metabolic variables during pregnancy and after delivery is required to early diagnose cardiovascular risk factors, especially in high risk population

Introducción: los cambios del perfil lipídico durante el embarazo se relacionan probablemente con la estimulación estrogénica y la resistencia a la insulina. Diversas relaciones se han planteado entre el perfil lipídico gestacional, la intolerancia a la glucosa, la disfunción endotelial y el riesgo cardiovascular a largo plazo; sus efectos sobre el crecimiento fetal no son concluyentes. Dado que no existe un protocolo de diagnóstico y seguimiento de la dislipemia durante el embarazo, el objetivo del presente estudio fue evaluar la incidencia de dislipemia en pacientes con diabetes gestacional (DMG) y analizar su relación con complicaciones maternas, fetales y variables de síndrome metabólico 3 y 12 meses tras el parto. Pacientes y métodos: fueron incluidos 250 pacientes con DMG. Se analizaron variables clínicas maternas y del recién nacido y se determinó el perfil lipídico durante el embarazo, 3 y 12 meses tras el parto. La incidencia de dislipemia se realizó utilizando dos clasificaciones diferentes. Resultados: las alteraciones más frecuentes fueron bajos niveles de HDL y altos de triglicéridos (TG). La prematuridad o el peso al nacer no se relacionaron con la presencia de dislipemia. El parámetro lipídico que mejor predijo el riesgo de macrosomía fueron los TG. Altos niveles de TG tres meses después del parto se relacionaron con macrosomía y variables de síndrome metabólico pregestacional, así como 3 y 12 meses después del parto. Conclusiones: los niveles de TG durante el embarazo representan el parámetro que mejor predice el riesgo de macrosomía y se relacionan con un mayor riesgo metabólico después del parto. La evaluación del perfil lipídico durante el embarazo y después del parto permite un diagnóstico precoz de factores de riesgo cardiovascular, especialmente en poblaciones de alto riesgo

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

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.

Arterial Calcium Stimulation with Hepatic Venous Sampling in the Localization Diagnosis of Endogenous Hyperinsulinism.

Objective. The aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization diagnosis of endogenous hyperinsulinism. Patients and Methods. A retrospective descriptive study was performed including patients with endogenous hyperinsulinism who underwent ASVS. The histopathological diagnosis in patients who underwent a surgical procedure was used as the reference for the statistical study of the accuracy of this technique. Results. 30 patients were included with endogenous hyperinsulinism and nonconclusive imaging diagnosis was included. ASVS was performed in all cases. Surgery was performed in 20 cases. Insulinoma was removed in 19 patients; the location of all cases was detected in the ASVS. All cases of endogenous hyperinsulinism had a positive result for the ASVS, with this association being statistically significant (χ2 = 15.771; p < 0.001). A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (K = 0.518, p < 0.001). Conclusions. ASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism undetected by other imaging tests. This technique allows the localization of intrapancreatic insulinomas and represents useful tool for the diagnosis and surgical management of these tumors.

Evaluación de la efectividad del tratamiento con glucocorticoides intravenosos en la oftalmopatía de Graves / Obesity: etiologic and pathophysiological analysis

Objetivo: Evaluar la efectividad del protocolo de tratamiento intermitente con glucocorticoides a altas dosis por vía intravenosa (i.v.) en la oftalmopatía de Graves (OG) moderada-grave del Hospital Reina Sofía. Material y métodos Se incluyeron los pacientes con OG tratados con glucocorticoides i.v. en nuestro servicio desde agosto de 2007 a agosto de 2011. Se administró prednisolona i.v. en dosis de 7,5mg/kg/d 2d alternos durante 6 semanas alternas y mitad de la dosis durante 6 semanas más. Resultados Analizamos 18 pacientes (83,3% mujeres) con una edad media de 43±11 años. Cuatro eran fumadores, 5 habían dejado el hábito y el resto nunca habían fumado. El 66,7% presentaban hipertiroidismo por enfermedad de Graves, de los cuales el 41,6% habían recibido radioyodo. La respuesta al tratamiento fue buena en el 72,2%, parcial en 11,1% y mala en 16,7%. En 5 aparecieron efectos secundarios leves. Antes del tratamiento el 83,3% presentaron diplopía, el 33,3% retracción palpebral, el 72,2% dolor ocular y el 44,4% exoftalmos. Después del tratamiento solo el 33,3% continuaron con diplopía (p=0,004), el 5,6% con retracción palpebral (p=0,063), el 16,7% con dolor ocular (p=0,002) y el 11,1% con exoftalmos (p=0,031). El 22,2% precisaron radioterapia. La respuesta al tratamiento no se asoció a la enfermedad de base (p=0,866) al haber recibido radioyodo previo como tratamiento del hipertiroidismo (p=0,447) o al ser fumador (p=0,368).Conclusiones El tratamiento con glucocorticoides i.v. en la oftalmopatía tiroidea reduce significativamente la diplopía, el dolor ocular y el exoftalmos. Los efectos secundarios son leves y poco frecuentes. La respuesta al tratamiento es independiente de la enfermedad de base, de haber recibido radioyodo y de ser fumador (AU)

Objective: To assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves’ ophthalmopathy (GO).Materials and methods: Patients with GO treated with IV GCs from August 2007 to August 2011at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulseprednisol one (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks. Results: Eighteen patients (mean age, 43+/-11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves’ disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment,83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P = .004), 5.6% eyelid retraction (P = .063), 16.7% eye pain(P = .002), and 11.1% exophthalmos (P = .031). Response to treatment was not related to the underlying disease (P = .866), prior radioiodine treatment (P = .447), or smoking status (P = .368).Conclusions: Intravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status (AU)

Clinical efficacy of intravenous glucocorticoid treatment in Graves' ophtalmopathy.

OBJECTIVE: To assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves' ophthalmopathy (GO). MATERIALS AND METHODS: Patients with GO treated with IV GCs from August 2007 to August 2011 at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulse prednisolone (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks. RESULTS: Eighteen patients (mean age, 43 ± 11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves' disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in 11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment, 83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P=.004), 5.6% eyelid retraction (P=.063), 16.7% eye pain (P=.002), and 11.1% exophthalmos (P=.031). Response to treatment was not related to the underlying disease (P=.866), prior radioiodine treatment (P=.447), or smoking status (P=.368). CONCLUSIONS: Intravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status.

[Usefulness of arterial calcium stimulation with hepatic venous sampling in the localization diagnosis of endogenous hyperinsulinism]. / Valoración de la utilidad del test de estimulación intraarterial con calcio en el diagnóstico de localización del hiperinsulinismo endógeno.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization of tumors in patients with endogenous hyperinsulinism not detected with other methods. PATIENTS AND METHODS: We performed a retrospective study of 26 patients admitted to our hospital for hypoglycemia who underwent ASVS because the source of hyperinsulinism was not clearly identified by other imaging techniques. The histopathological result in patients who underwent a surgical procedure was considered the reference for statistical study of the accuracy of this technique. Statistical analysis was performed by comparing proportions with the chi-squared test with Yates' correction for contingency tables, and Cohen's kappa coefficient as a measure of interrater agreement between two observations. RESULTS: Surgery was performed in 17 patients, 13 with positive ASVS and the remaining four with negative results. An insulinoma was removed in 12 patients, and 10 of these were detected in the ASVS. A total of 76.9 % of positive ASVS tests corresponded to a histological diagnosis of insulinoma, and 83% of these insulinomas were positive in ASVS. This association was statistically significant (chi cuadrado=7.340; p=0.012). Two of three patients with nesidioblastosis had a positive response in the ASVS. A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (kappa=0.556, p = 0.007). CONCLUSIONS: ASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism not detected by other imaging tests. This technique allows tumors in the pancreatic gland to be identified and may be useful in the choice of the surgical technique to be used.

Valoracion de la utilidad del test de estimulacion intraarterial con calcio en el diagnostico de localizacion del hiperinsulinismo endogeno / Usefulness of arterial calcium stimulation with hepatic venous sampling in the localization diagnosis of endogenous hyperinsulinism

Antecedentes y objetivo El objetivo de este estudio fue valorar la utilidad del test de estimulación intraarterial con calcio (TEIC) en el diagnostico de localización del hiperinsulinismo endogeno no detectado por otros métodos. Pacientes y métodos Estudio retrospectivo de 26 pacientes ingresados por hipoglucemias en los que se realizo un TEIC, ya que la localización del hiperinsulinismo no fue claramente establecida con otras técnicas de imagen. En los pacientes que recibieron cirugía se pudo establecer el diagnostico anatomopatologico, y este se considero el patrón de referencia para la validación del TEIC. El análisis estadístico se realizo mediante la comparación de proporciones por el test chi-cuadrado con corrección de Yates para tablas de contingencia y el coeficiente (..) (AU)

Background and objective The aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization of tumors in patients with endogenous hyperinsulinism not detected with other methods. Patients and methods We performed a retrospective study of 26 patients admitted to our hospital for hypoglycemia who underwent ASVS because the source of hyperinsulinism was not clearly identified by other imaging techniques. The histopathological result in patients who underwent a surgical procedure was considered the reference for statistical study of the accuracy of this technique. Statistical analysis was performed by comparing proportions with the chi-squared test with Yates¡¯ correction for contingency tables, and Cohen¡äs kappa coefficient as a measure of interrater agreement between two observations. Results Surgery was performed in 17 patients, 13 with positive ASVS and the remaining four with negative results. An insulinoma was removed in 12 patients, and 10 of these were detected in the ASVS. A total of 76.9 % of positive ASVS tests corresponded to a histological diagnosis of insulinoma, and 83% of these insulinomas were positive in ASVS. This association was statistically significant (chi cuadrado=7.340; p=0.012). Two of three patients with nesidioblastosis had a positive response in the ASVS. A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (¦Ê=0.556, p = 0.007).Conclusions ASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism not detected by other imaging tests. This technique allows tumors in the pancreatic gland to be identified and may be useful in the choice of the surgical technique to be used (AU)