Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.

Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of tumors with growing incidence. Recent molecular analyses provided a precise picture of their genomic and epigenomic landscape. Splicing dysregulation is increasingly regarded as a novel cancer hallmark influencing key tumor features. We have previously demonstrated that splicing machinery is markedly dysregulated in PanNETs. Here, we aimed to elucidate the molecular and functional implications of CUGBP ELAV-like family member 4 (CELF4), one of the most altered splicing factors in PanNETs. CELF4 expression was determined in 20 PanNETs, comparing tumor and non-tumoral adjacent tissue. An RNA sequencing (RNA-seq) dataset was analyzed to explore CELF4-linked interrelations among clinical features, gene expression, and splicing events. Two PanNET cell lines were employed to assess CELF4 function in vitro and in vivo. PanNETs display markedly upregulated CELF4 expression, which is closely associated with malignancy features, altered expression of key tumor players, and distinct splicing event profiles. Modulation of CELF4 influenced proliferation in vitro and reduced in vivo xenograft tumor growth. Interestingly, functional assays and RNA-seq analysis revealed that CELF4 silencing altered mTOR signaling pathway, enhancing the effect of everolimus. We demonstrate that CELF4 is dysregulated in PanNETs, where it influences tumor development and aggressiveness, likely by modulating the mTOR pathway, suggesting its potential as therapeutic target.

Comparative Study of the Efficacy of EHO-85, a Hydrogel Containing Olive Tree (Olea europaea) Leaf Extract, in Skin Wound Healing.

Olive tree (Olea europaea) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort (Centella asiatica), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.

Bone metastases from differentiated thyroid cancer: characteristics and prognostic factors in a multicenter series.

Objective: The aim of this study is to describe the characteristics, survival and prognostic factors of a cohort of patients with bone metastases (BMs) from differentiated thyroid carcinoma (DTC). Methods: This was a multicenter retrospective observational study including patients diagnosed with BMs from DTC between 1980 and 2021. A Cox regression was performed to study prognostic factors for 5- and 10-year survival. Kaplan-Meier and log-rank tests were performed for the survival analysis and comparison between groups. Results: Sixty-three patients were evaluated. Median follow-up from BM diagnosis was 35 (15-68) months. About 30 (48.4%) patients presented with synchronous BMs. Regarding histology, 38 (60.3%) had the papillary variant. BMs were multiple in 32 (50.8%) patients. The most frequent location was the spine (60.3%). Other metastases were present in 77.8%, mainly pulmonary (69.8%). Concerning treatment, 54 (85.9%) patients received I131, with BM uptake in 31 (49.2%) and 25 (39.7%) received treatment with multikinase inhibitors. Regarding complications, 34 (54%) patients had skeletal-related events, 34 (54%) died and 5- and 10-year overall survival was 42.4% and 20.4%, respectively. Significant prognostic factors in the multivariate analysis were the presence of lymph node involvement (hazard ratio (HR): 2.916; 95% confidence interval (CI): 1.013-8.391; P = 0.047) and treatment with I131 (HR 0.214 (95% CI 0.069-0.665); P = 0.008) at 5 years, the presence of other metastases (HR 6.844. 95% CI 1.017-46.05; P = 0.048) and treatment with I131 (HR 0.23 (95% CI 0.058-0.913); P = 0.037) at 10 years. Conclusions: Our study reflects the management of patients with bone metastases from differentiated thyroid carcinoma in real clinical practice in several centers in southern Spain. Overall survival at 5 and 10 years was lower in patients who were not treated with I131, had nodal involvement and/or had other metastases.

Standard Hypercaloric, Hyperproteic vs. Leucine-Enriched Oral Supplements in Patients with Cancer-Induced Sarcopenia, a Randomized Clinical Trial.

(1) Background: Malnutrition frequently affects patients with cancer, and it negatively impacts treatment tolerance, clinical outcomes and survival. Thus, appropriate nutritional screening and early nutrition support are extremely recommended. Currently, a significant number of oral supplements (OS) are commercially available; despite this, there is a lack of evidence for recommending specific OS, including leucine-enriched OS, for nutritional support in patients with cancer. (2) Aim: To compare the clinical evolution of patients with cancer (undergoing systemic treatment) that received standard hypercaloric, whey protein-based hyperproteic oral supplements vs. hypercaloric, hyperproteic leucine-enriched OS using a novel morphofunctional nutritional evaluation. (3) Patients and methods: This paper details an open-label, controlled clinical study in which patients were randomly assigned to receive nutritional treatment with whey protein-based hyperproteic oral supplements (control group) vs. hypercaloric, hyperproteic leucine-enriched OS (intervention group) during a twelve-week period. Forty-six patients were included; epidemiological, clinical, anthropometric, ultrasound (muscle echography of the rectus femoris muscle of the quadriceps and abdominal adipose tissue) and biochemical evaluation were performed. All patients received additional supplementation with vitamin D. (4) Results: Nutritional parameters (including bioimpedance, anthropometric, ultrasound and biochemical variables) of all included patients remained stable after the nutritional intervention. Extracellular mass tended to increase in the patients that received the leucine-enriched formula. Functionality (evaluated through the stand-up test) improved in both groups (p < 0.001). Prealbumin, transferrin levels and superficial adipose tissue increased in the control group (p < 0.05), while self-reported quality of life improved in all the evaluated patients (p < 0.001). (5) Conclusions: Nutritional support with hypercaloric, hyperproteic (with whey protein) OS and vitamin D supplementation were associated with the maintenance of body composition and improvements in functionality and in quality of life in the patients with cancer undergoing systemic treatment. No significant benefits were observed when a leucine-enriched formula was used.

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.

Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition.

Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.

Influence of Dipeptidyl Peptidase-4 (DPP4) on Mesenchymal Stem-Cell (MSC) Biology: Implications for Regenerative Medicine - Review.

Dipeptidyl peptidase IV (DPP4) is a ubiquitous protease that can be found in membrane-anchored or soluble form. Incretins are one of the main DPP4 substrates. These hormones regulate glucose levels, by stimulating insulin secretion and decreasing glucagon production. Because DPP4 levels are high in diabetes, DPP4 inhibitor (DPP4i) drugs derived from gliptin are widespread used as hypoglycemic agents for its treatment. However, as DPP4 recognizes other substrates such as chemokines, growth factors and neuropeptides, pleiotropic effects have been observed in patients treated with DPP4i. Several of these substrates are part of the stem-cell niche. Thus, they may affect different physiological aspects of mesenchymal stem-cells (MSC). They include viability, differentiation, mobilization and immune response. MSC are involved in tissue homeostasis and regeneration under both physiological and pathological conditions. Therefore, such cells and their secretomes have a high clinical potential in regenerative medicine. In this context, DPP4 activity may modulate different aspects of MSC regenerative capacity. Therefore, the aim of this review is to analyze the effect of different DPP4 substrates on MSC. Likewise, how the regulation of DPP4 activity by DPP4i can be applied in regenerative medicine. That includes treatment of cardiovascular and bone pathologies, cutaneous ulcers, organ transplantation and pancreatic beta-cell regeneration, among others. Thus, DPP4i has an important clinical potential as a complement to therapeutic strategies in regenerative medicine. They involve enhancing the differentiation, immunomodulation and mobilization capacity of MSC for regenerative purposes.

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells.

Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide.

Calcitriol-Mediated Hypercalcemia, Somatostatin Receptors Expression and 25-Hydroxyvitamin D3-1α- Hydroxylase in GIST Tumors.

Hypercalcemia is a common complication in cancer patients Mainly caused by Parathyroid hormone-related protein (PTHrP) secretion and metastasis. Calcitriol secretion is a rare source of hypercalcemia in solid tumors, especially in gastrointestinal stromal tumors (GIST). We present a case report of a female patient with a 23 cm gastric GIST that expressed somatostatin-receptors and presented with severe hypercalcemia due to calcitriol secretion. Calcium control was achieved with medical treatment before the use of targeted-directed therapies. Surgery was performed and allowed complete tumor resection. Two years later, patient remains free of disease. Molecular analysis revealed the mRNA expression of 25-hydroxyvitamin D3-1-hydroxylase (1αOHase) and vitamin-D receptors in the tumor cells, confirming the calcitriol-mediated mechanism. Furthermore, the expression of the endotoxin recognition factors CD14 and TLR4 suggests an inflammatory mediated mechanism. Finally, the expression of somatostatin-receptors, especially SST2 might have been related with clinical evolution and prognosis in this patient.

Sarcopenia and Ghrelin System in the Clinical Outcome and Prognosis of Gastroenteropancreatic Neuroendocrine Neoplasms.

BACKGROUND: Malnutrition and sarcopenia affect clinical outcomes and treatment response in cancer patients. Patients with neuroendocrine neoplasms (NENs) may present with additional symptoms related to tumor localization in the gastrointestinal tract and hormone secretion, increasing the risk and effects of sarcopenia. AIM: To explore the presence of malnutrition and sarcopenia in gastroenteropancreatic (GEP)-NEN patients, their relation to tumor characteristics, patient outcomes, survival and the molecular expression of ghrelin system components in the tumor. PATIENTS AND METHODS: One-hundred-and-four patients were included. Anthropometric, biochemical and CT-scans at diagnosis were evaluated. The expression levels of key ghrelin system components were assessed in 63 tumor samples. RESULTS: Nutritional parameters were similar in GEP-NEN tumors of different origin. Relapsed disease was associated with decreased BMI. Patients who presented with weight loss at diagnosis had significantly lower overall survival (108 (25-302) vs. 263 (79-136) months). Ghrelin O-acyltransferase (GOAT) enzyme expression was higher in these patients. The prevalence of sarcopenia using CT images reached 87.2%. Mortality was observed only in patients with sarcopenia. Muscle evaluation was correlated with biochemical parameters but not with the expression of ghrelin system components. CONCLUSION: Survival is related to the nutritional status of patients with GEP-NENs and also to the molecular expression of some relevant ghrelin system components. Routine nutritional evaluation should be performed in these patients, in order to prescribe appropriate nutritional support, when necessary, for increasing quality of life and improving clinical outcomes.

Effects of Ketoconazole on ACTH-Producing and Non-ACTH-Producing Neuroendocrine Tumor Cells.

Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptotic effect of ketoconazole in human cancer cells was previously suggested. The aim of this study was to explore the effects of ketoconazole on ACTH-producing and non-ACTH-producing neuroendocrine tumor (NET) cell lines. The effects of ketoconazole alone, and in combination with somatostatin analogs, were evaluated in two human cell lines: DMS-79 (ectopic ACTH-producing small cell lung carcinoma) and BON-1 (human pancreatic NET). Total DNA measurement, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC) expression by qRT-PCR, serotonin, CgA, and ACTH secretion assays were performed. In both cell lines, ketoconazole significantly suppressed cell growth and colony formation in a dose and time-dependent manner. The effect in DMS-79 was primarily cytotoxic, while it was more apoptotic in BON-1 cells. Ketoconazole also induced increase in G0/G1 phase in both cell lines and arrest in phase G2/M of BON-1 cells. Ketoconazole did not affect the secretion of serotonin, CgA, ACTH, or the mRNA expression of CgA and POMC. Decreased serotonin secretion was observed after the combination treatment with pasireotide. These results suggest a direct effect of ketoconazole on cell proliferation, apoptosis, and cell cycle in both ACTH- and non-ACTH-producing NET cells.

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.

Early nutrition support therapy in patients with head-neck cancer.

BACKGROUND: weight loss is commonly observed in head-neck cancer patients, affecting 75-80% of them during their treatment period; weight loss is severe in 30-50% of cases. According to ESPEN publications, nutritional assessment in cancer patients should be frequently performed and nutrition support therapy must be started when any deficiency is observed. OBJECTIVE: to evaluate the effect of early nutrition support (ENS) in nutritional markers and treatment response in patients with head-neck cancer receiving radiotherapy (RT). PATIENTS AND METHODS: one hundred and two patients with head-neck cancer and more than two points in the malnutrition screening tool (MUST) before receiving RT were included. ENS was provided to all patients consisting in nutrition counselling, oral supplements and/or enteral nutrition. RESULTS: one hundred and two patients were included; 76% had a stage IV of disease. At the end of RT, after ENS, a slightly decreased body mass index (BMI) with an increased fat-free body mass was observed (p < 0.001); biochemical nutrition parameters remained stable despite decreased oral intake. Less than 40% of patients had severe epithelitis or mucositis; 92% of patients received the total amount and doses of originally planned RT sessions, while 22.8% required RT-sessions interruption. Patients with caloric malnutrition had a lower fulfillment of RT than those without caloric malnutrition (p < 0.001). Mortality was related to lower Karnosfsky, higher weight loss before RT and higher grade of mucositis/epitelitis (p < 0.05). CONCLUSIONS: patients who receive ENS keep their nutritional condition instead of associated effects due to RT. ENS represents an efficient treatment and could prevent malnutrition associated comorbidities in oncologic patients.

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.

[Percutaneous endoscopic gastrostomy in a myotrophic lateral sclerosis. Experience in a district general hospital]. / Gastrostomía endóscopica percutánea en esclerosis lateral amiotrófica; experiencia en un hospital de tercer nivel.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder that affects the pyramidal tract, producing progressive motor dysfunctions leading to paralysis. These patients can present with dysphagia, requiring nutritional support with a nasogastric tube or Percutaneous Endoscopic Gastrostomy (PEG). PEG is associated with increased survival rates. However, the timing of PEG placement remains a significant issue for clinicians. OBJECTIVE: To analyse the characteristics of ALS patients at the moment of PEG placement and their progression. METHODS AND MATERIALS: Descriptive retrospective study including patients diagnosed with ALS and PEG who were assessed during the 2005-2014 period in our hospital. Nutritional parameters and respiratory function were assessed for all patients, as well as their progression. The data was analysed using SPSS15. RESULTS: 37 patients were included (56.8% men, 43.2% women) with an average age of 60 at diagnosis, and an average age of 63.1 at PEG placement. 48.6% started with spinal affection and 51.4%, with bulbar affection. 43.2% of the patients received oral nutritional supplements prior to PEG placement for a mean period of 11.3 months. The mean forced vital capacity at diagnosis was 65.45±13.67%, with a negative progression up to 39.47±14.69% at the moment of PEG placement. 86.5% of patients required non-invasive positive-pressure ventilation. 86.5% presented with dysphagia, 64.9% with weight loss > 5-10% from their usual weight, 8.1% with low Body Mass Index, 27% with malnutrition and 73% with aworsened breathing function; therefore, 100% met the criteria for PEG placement according to our protocol. The period on enteral feeding was extended for 10.1 months with a mortality of 50% during the first 6 months from PEG placement. CONCLUSIONS: There is evidence of a 3-year delay between diagnosis and PEG placement, with a survival rate of 50% at 6 months from PEG insertion. Further studies are required to establish whether an earlier placement might increase survival rates.

Introducción: La Esclerosis Lateral Amiotrófica (ELA) es una enfermedad degenerativa neurológica con afectación de la vía piramidal, produciendo trastornos motores progresivos que evolucionan hasta la parálisis. Estos pacientes pueden asociar disfagia, precisando soporte nutricional a través de de sonda nasogástrica o Gastrostomía Endoscópica Percutánea (PEG). La PEG está asociada con aumento de la supervivencia, sin embargo la evidencia acerca del momento óptimo para su colocación es escasa. Objetivo: Analizar las características de los pacientes con ELA en el momento de colocación de la PEG y su evolución. Material y métodos: Estudio descriptivo retrospectivo. Se incluyeron pacientes con diagnóstico de ELA y PEG valorados durante los años 2005-2014 en nuestro hospital. Se analizaron parámetros nutricionales y respiratorios, y evolución de los pacientes. Los resultados se analizaron en el programa SPSS15. Resultados: 37 pacientes fueron incluidos (56,8% hombres, 43,2% mujeres) con una edad media al diagnóstico 60 años, y edad media de colocación de PEG de 63,1 años, el 48,6% debutó con afectación espinal y el 51,4%, con bulbar. El 43,2% de los pacientes recibieron suplementos previa colocación de PEG durante un promedio de 11,3 meses. La capacidad vital forzada (CVF) media al diagnóstico fue del 65,45±13,67%, evolucionando desfavorablemente hasta un 39,47±14,69% en el momento de colocación de la PEG. El 86,5% de los pacientes precisaron soporte respiratorio con ventilación mecánica no invasiva (VMNI). El 86,5% presentaron disfagia, el 64,9% pérdida de peso > 5-10% de su peso habitual, el 8,1% IMC bajo, el 27% parámetros bioquímicos de desnutrición y el 73% empeoramiento de función respiratoria, por tanto, el 100% cumplían criterios de colocación de PEG según nuestro protocolo. La duración de la nutrición enteral fue de 10,1 meses con una mortalidad del 50% en los primeros 6 meses de la colocación de la PEG. Conclusiones: Evidenciamos una demora de 3 años entre el diagnóstico y la colocación de la PEG, con una supervivencia del 50% a los 6 meses de la realización de la misma. Más estudios son necesarios para determinar si una colocación más precoz podría aumentar la supervivencia.

[Screening for Cushing's syndrome in obese patients; is it really necessary?]. / Despistaje rutinario de síndrome de Cushing en pacientes con obesidad mórbida: ¿es realmente necesario?

to be more frequent among patients with metabolic syndrome. Previous studies have suggested to perform a routine screening for CS in obese patients; however, more recent reports only recommend a case-finding approach in patients with uncontrolled diabetes and hypertension, despite appropriate treatment. Objective: The aim of this study was to evaluate the prevalence of unsuspected CS in morbidly obese patients in an outpatient's clinic. Patients and methods: Retrospective case-note study. We reviewed the medical records of morbidly obese patients referred to our clinic prior to bariatric surgery between january 2001 and december 2011. All patients had a complete medical history including physical examination, and 399 underwent screening for CS as part of our pre-surgical protocol. As screening for autonomous cortisol secretion, we performed an overnight 1 mg Dexamethasone Suppression Test (DST). Serum cortisol < 1.8 µg/dl was the cut-off point for normal suppression. Results: 399 patients (308 female; mean age 41.9 ± 10.5 years; mean BMI 51.5 ± 8.4 kg/m2). In the retrospective analysis, prediabetes and diabetes mellitus were observed in 10.3% and 27.8% respectively. In 21 of 399 patients, screening was considered to be abnormal. Eight of these 21 patients had subsequent normal 24h Urinary Free Cortisol (UFC) levels (150 µg/24h). In 13 of 20 patients, we repeated an overnight 1mg DST, on suspicion of failing to take the dexamethasone correctly. Three patients failed to suppress their cortisol levels, two of them were on carbamazepine, which was considered to be a false positive result. The other patient with abnormal UFC levels was diagnosed with CS (0.26%), whose cause was a pituitary microadenoma. Conclusion: A low proportion of patients with morbid obesity were found to have CS. Our findings suggest that morbidly obese patients should not be routinely screened for CS.

Introducción: El síndrome de Cushing (SC) es más frecuente en pacientes con síndrome metabólico. Estudios previos han sugerido que es necesario realizar un despistaje de SC en pacientes obesos; sin embargo, estudios más recientes sólo recomiendan el despistaje en pacientes con hipertensión o diabetes mal controlados, a pesar de tratamiento. Objetivo: Evaluar la prevalencia de SC oculto en pacientes con obesidad mórbida. Pacientes y métodos: Estudio observacional retrospectivo en el que se incluyeron 399 pacientes que iban a someterse a cirugía bariátrica. A todos los pacientes se les realizó una historia clínica completa, incluyendo exploración física y test de Nugent, como parte del protocolo precirugía. Resultados: 399 pacientes (308 mujeres, edad media 41,9 ± 10,5 años; IMC medio 51,5 ± 8,4 kg/m2). El 10,3% de los pacientes presentaban prediabetes y el 27,8% diabetes. En 21 de los 399 pacientes, el despistaje fue anormal. En 8 pacientes, medimos cortisol libre en orina de 24 horas (CLU), siendo en todos normal al menos en dos ocasiones (CLU < 150 mcg/24 h), lo que descartaba SC. En 13 pacientes, repetimos el test de Nugent; sólo en 3, el test resultó patológico. Dos de los pacientes estaban en tratamiento con carbamacepina, lo que se consideró un falso positivo. El otro paciente se diagnosticó de Enfermedad de Cushing. Conclusión: La prevalencia de SC fue muy baja en pacientes con obesidad mórbida. Nuestros datos sugieren que no se debería realizarse un despistaje de SC de forma rutinaria.

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.