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

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

[Hypophosphatemia associated with use of intravenous ferric carboxymaltose]. / Hipofosfatemia asociada a uso de carboximaltosa férrica endovenosa.

Introduction: Introduction: ferric carboxymaltose (CF) is an intravenous preparation that helps the rapid correction of anemia with a lower risk of adverse reactions. However, an association has been found between the administration of CF and the development of hypophosphatemia. Case report: we present the clinical case of a 57-year-old patient with a history of iron de-ficiency anemia who, after receiving treatment with CF (Ferinjet®) chronically, develops a clinical of severe muscle weakness. Laboratory tests showed hypophosphatemia, normocalcemia, normal vitamin D level (after correction) and increased renal excretion of phosphorus. After study, the diagnosis of chronic hypophosphatemia secondary to the use of CF is reached. Discussion: CF can cause an increase in FGF-23 which acts at the renal level inducing phosphaturia, which can generate severe hypophosphatemia. This case demonstrates the importance of recognizing and treating this clinical entity in time.

Introducción: Introducción: la carboximaltosa férrica (CF) es una preparación intravenosa que ayuda a la corrección rápida de anemia con menor riesgo de reacciones adversas. Sin embargo, se ha encontrado asociación entre la administración de la CF y el desarrollo de hipofosfatemia. Caso clínico: presentamos el caso clínico de una paciente de 57 años con anemia ferropénica que tras recibir tratamiento con CF (Ferinjet®) de forma crónica, desarrolla un cuadro clínico de debilidad muscular severa. En la analítica se aprecia hipofosfatemia, normocalcemia, nivel de vitamina D normal (tras corrección) y aumento de excreción renal de fósforo. Tras estudio se llega al diagnóstico de hipofosfatemia crónica secundaria al uso de la CF. Discusión: la CF puede provocar un aumento de FGF-23 el cual actúa a nivel renal induciendo fosfaturia, pudiendo generar hipofosfatemia grave. Este caso demuestra la importancia de reconocer y tratar esta entidad clínica a tiempo.

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

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

[Behçet disease with isolated ACTH deficiency]. / Enfermedad de Behçet asociada a déficit de corticotropina.

We report a case of a patient with longstanding Behçet disease, with neurological symptoms predominantly, who became hospitalized for adrenal insufficiency, caused by isolated deficiency of corticotropin (DAACTH). DAACTH is a typical characteristic of hypophysitis, reported in association with many autoimmune diseases. Nevertheless, hypothalamic-pituitary injury in Behçet disease is exceptional. We review the literature and possible mechanisms of this association until now not reported.

Relationship between thyroid dysfunction and body weight: a not so evident paradigm.

PURPOSE: Hypothyroidism has traditionally been associated with obesity, whereas hyperthyroidism has been linked to being underweight. However, very few studies have assessed these associations. The aim of this work is to evaluate the association between thyroid dysfunction and body mass index (BMI) at baseline and after normalization of the hormone levels. PATIENTS AND METHODS: A retrospective, observational study of a cohort of otherwise healthy patients that were referred for evaluation of thyroid dysfunction to the Endocrine Department of Pontevedra University Complex Hospital, Spain was conducted. We collected data of BMI and thyroid hormone levels before treatment and after normalization of thyroid function within a follow-up period of 12 months. RESULTS: A total of 330 patients were initially selected for the study. In order to exclude variables that for any reason could influence on BMI, 235 were excluded for further studies. Another 61 patients were also excluded because incomplete data on their medical records, failure to achieve euthyroidism, or lost to follow-up. Therefore, the eligible final study group consisted of 34 patients (17 with hypothyroidism and 17 with hyperthyroidism). No differences were observed in mean baseline BMI between hypo and hyperthyroid patients (27.07±3.22 vs 26.39±4.44, p=0.609). Overweight or obesity was observed in 76.5% and 58.8% of hypothyroid and hyperthyroid patients, respectively (p=0.23). After normalization of thyroid function, the weight of hypothyroid patients decreased from 70.93±10.06 kg to 68.68±10.14 (p=0.000), while the weight of hyperthyroid patients increased from 65.45±11.64 kg to 68.37±12.80 (p=0.000). Their mean BMI was 26.22±3.36 and 27.57±4.98 (p=0.361) for hypo- and hyperthyroid patients, respectively. 58.8% and 64.7% patients remained in the overweight/obesity range in each group (p=0.72). CONCLUSION: Untreated thyroid dysfunction is not associated with BMI. Normalization of thyroid levels significantly changed the weight of patients, but remaining most patients within overweight ranges.

Hipofosfatemia asociada a uso de carboximaltosa férrica endovenosa / Hypophosphatemia associated with use of intravenous ferric carboxymaltose

Introducción: la carboximaltosa férrica (CF) es una preparación intravenosa que ayuda a la corrección rápida de anemia con menor riesgo de reacciones adversas. Sin embargo, se ha encontrado asociación entre la administración de la CF y el desarrollo de hipofosfatemia. Caso clínico: presentamos el caso clínico de una paciente de 57 años con anemia ferropénica que tras recibir tratamiento con CF (Ferinjet®) de forma crónica, desarrolla un cuadro clínico de debilidad muscular severa. En la analítica se aprecia hipofosfatemia, normocalcemia, nivel de vitamina D normal (tras corrección) y aumento de excreción renal de fósforo. Tras estudio se llega al diagnóstico de hipofosfatemia crónica secundaria al uso de la CF. Discusión: la CF puede provocar un aumento de FGF-23 el cual actúa a nivel renal induciendo fosfaturia, pudiendo generar hipofosfatemia grave. Este caso demuestra la importancia de reconocer y tratar esta entidad clínica a tiempo. (AU)

Introduction: ferric carboxymaltose (CF) is an intravenous preparation that helps the rapid correction of anemia with a lower risk of adverse reactions. However, an association has been found between the administration of CF and the development of hypophosphatemia. Case report: we present the clinical case of a 57-year-old patient with a history of iron de-ficiency anemia who, after receiving treatment with CF (Ferinjet®) chronically, develops a clinical of severe muscle weakness. Laboratory tests showed hypophosphatemia, normocalcemia, normal vitamin D level (after correction) and increased renal excretion of phosphorus. After study, the diagnosis of chronic hypophosphatemia secondary to the use of CF is reached. Discussion: CF can cause an increase in FGF-23 which acts at the renal level inducing phosphaturia, which can generate severe hypophosphatemia. This case demonstrates the importance of recognizing and treating this clinical entity in time. (AU)

Hipocortisolismo hipofisario por sobrecarga férrica en un paciente conAnemia de Blackfan-Diamond / Pituitary hypocortisolism due to iron overload in a patient with Blackfan-Diamond anemia

Iron overload in the context of a Blackfan-Diamond anemia is a extremely uncommon cause of central adrenal insufficiency. We report apatient with Blackfan-Diamond anemia diagnosis during his childhood.Ten years later, as a consequence of iron overload caused by repeatedtransfusions, he developed central hypocortisolism. Blackfan-Diamondanemia is a hereditary syndrome characterized by erythroid aplasia,predisposition to hematologic and solid organ malignancies and congenital abnormalities.Endocrine complications of Blackfan-Diamond anemia are reported inthe literature and highly variable. Hypocortisolism is considered as anuncommon complication (0.7-4 %). Therefore, in a patient with repeated transfusions, we must considerer in a possible ACTH deficiency inthe context of hemochromatosis due to iron overload. (AU)

Las causas de insuficiencia adrenal de origen central son múltiples,siendo la sobrecarga férrica en el seno de una anemia de Blackfan-Diamond extremadamente infrecuente. Se presenta el caso de un pacientede 15 años diagnosticado de anemia de Blackfan-Diamond en la infancia que desarrolla hipocortisolismo de origen central como consecuencia de la sobrecarga férrica por transfusiones de repetición comotratamiento de soporte de la anemia. La anemia de Blackfan-Diamondes un síndrome hereditario caracterizado por una aplasia eritroide queconlleva un recuento reducido de glóbulos rojos, anomalías congénitasy predisposición a neoplasias hematológicas y de órganos sólidos. Laprevalencia de las complicaciones endocrinas reportadas en la literatura secundarias a esta patología es muy variable siendo el hipocortisolismo muy poco frecuente (0,7-4 %).Por ello, ante un paciente contransfusiones de repetición, debemos tener en cuenta el posible déficitde ACTH en en el contexto de una hemocromatosis por sobrecarga férrica. (AU)

Manejo de la ascitis quilosa y revisión de la literatura / Management of chylous ascites and review of literature

Introducción: La ascitis quilosa es la acumulación de líquido linfático en la cavidad peritoneal. Se trata de una patología poco frecuente cuya causa puede ser traumática oatraumática, siendo la obstrucción por neoplasias abdominales la etiología más frecuente en adultos. No existe evidenciacientífica acerca de una terapia que resulte totalmente eficazen el tratamiento de esta patología. Objetivos: El objetivo fundamental de esta revisión esprofundizar, integrar, resumir y actualizar la información publicada sobre este tema, así como proporcionar informaciónútil y contrastada a otros compañeros para su aplicación en lapráctica clínica. Material y Métodos: Se realiza una revisión de la bibliografía empleando la base de datos PubMed, Medline y Sciencedirect con los descriptores “chylous ascitis” AND “diet”. Los filtros empleados fueron: humanos, últimos 5 años y lenguasespañola e inglesa. Se revisaron los artículos y se seleccionaron 12 trabajos. Resultados: Se describen las diferentes alternativas terapéuticas tanto dietéticas como el tratamiento intervencionista.Discusión: La ascitis quilosa supone un problema médicocomplejo por el potencial deterioro nutricional e inmunológico que genera. Revisada la literatura, existe poca evidenciacientífica sobre el tratamiento de elección en los pacientescon ascitis quilosa, aunque parece existir consenso de que ladieta es el tratamiento más simple y, habitualmente, el primero en implementarse. Debido a esta complejidad, es imprescindible la valoración del paciente por un equipo multidisciplinar y la actitud terapéutica elegida dependerá de lacausa de la ascitis, la situación clínica y la experiencia de losprofesionales sanitarios. Conclusiones: La terapia nutricional de la ascitis quilosase basa en una dieta baja en grasas suplementada con triglicéridos de cadena media y es el tratamiento de elección porsu alto porcentaje de eficacia.(AU)

Introduction: Chylous ascites is the accumulation oflymphatic fluid in the peritoneal cavity. It is a rare pathologyand it can be traumatic or no traumatic. The most commoncause of chylous ascites in adults is obstruction by abdominalneoplasms. There is insufficient evidence about an effectivetreatment. Objectives: The main objective of this review is to deepen, integrate, summarize and update the information published about this topic. Also, we want to provide to other healthprofessionals, a useful and verified information to applicate inclinical practice. Material and Methods: A literature review was made: PubMed, Medline and Science direct search using as descriptors “chylous ascites” AND “diet”. The following filters areused: human, last 5 years and Spanish/English languages.Articles were reviewed and 12 papers were selected. Results: We describe the dietary alternatives and the interventional treatment. Discussion: Chylous ascites is an important medical problem, because of the deterioration of immune system and nutritional parameters. Literature review was made and there isno scientific evidence about the treatment of choice in patients with chylous ascites. Diet is the simplest treatment andthe first to be implemented. A multidisciplinary team is important in the treatment of these patients. To choose the besttherapeutic attitude, we must know the cause, the clinical situation and the experience of health care workers. Conclusions: A lowfat diet supplemented with mediumchain triglycerides is the most efficacy treatment for chylousascites. There is no evidence about an effective treatment forthis pathology and most publications are clinical cases.Prospective, randomized studies are needed to get more evidence on the management of chylous ascites.(AU)

Asociación entre obesidad y embarazo cronológicamente prolongado: estudio retrospectivo observacional / Association between obesity and chronologically prolonged pregnancy: a retrospective observational study

Objetivos: Determinar si la obesidad, definida como índice de masa corporal (IMC) ≥30 kg/m2 al inicio del embarazo, es más frecuente en las gestaciones cronológicamente prolongadas (GCP), consideradas aquellas de 41 semanas o más, frente a los embarazos a término, y averiguar si existe relación entre las GCP y otras variables estudiadas. Material y métodos: Estudio retrospectivo observacional sobre una muestra seleccionada aleatoriamente de pacientes que dieron a luz en el Complejo Hospitalario de Pontevedra durante 2019. Resultados: N= 196 (98 GCP y 98 gestaciones a término). La prevalencia de obesidad en la primera consulta de embarazo fue del 23,5 % en las GCP y del 10,2 % en los embarazos a término (p= 0,013). El IMC promedio en las GCP estaba en el rango de sobrepeso y en las gestaciones a término en normopeso (p= 0,001). El porcentaje de partos instrumentales y cesáreas en las GCP fue del 20,4 y 22,4 %, respectivamente, estando en las gestaciones a término en un 15,3 y 4,1 % (p <0,001). La primiparidad (p <0,001) y la ganancia de peso por encima de las recomendaciones (p= 0,004) mostraron una asociación significativa con las GCP, mientras que la edad materna, el sexo fetal, el peso del recién nacido y el sobrepeso materno no. El análisis multivariante halló como factores de riesgo independientes de GCP: la primiparidad, el IMC ≥30 kg/m2 y la ganancia de peso por encima de las recomendaciones. Conclusiones: La obesidad al inicio del embarazo es un factor de riesgo de GCP, al igual que la primiparidad y la ganancia de peso mayor a la recomendada. Existe asociación entre las GCP y el parto instrumental y la cesárea. (AU)

Objectives: To determine whether obesity, defined as body mass index (BMI) ≥30 kg/m2 at the beginning of pregnancy, is more frequent in chronologically prolonged gestations (CPG), considered those of 41 weeks or more, versus term pregnancies, and to find out if there is a relationship between CPG and other variables studied. Material and methods: Retrospective observational study on a randomly selected sample of patients who gave birth at the Complejo Hospitalario de Pontevedra during 2019. Results: N=196 (98 CPG and 98 term gestations). The frequency of obesity at the first pregnancy visit was 23.5% in CPGs and 10.2% in term pregnancies (p=0.013). The average BMI in CPGs was in the overweight range and in term pregnancies in the normal weight range (p=0.001). The percentage of instrumental deliveries and cesarean sections in the CPGs was 20.4% and 22.4%, while in the term gestations it was 15.3% and 4.1% (p<0.001). Primiparity (p<0.001) and weight gain above recommendations (p=0.004) showed a significant association with CPG, while maternal age, fetal sex, newborn weight and maternal overweight did not. Multivariate analysis found as independent risk factors for CPG: primiparity, BMI ≥30 kg/m2 and weight gain above recommendations. Conclusions: Obesity in early pregnancy is a risk factor for CPG, as is primiparity and weight gain greater than recommended. There is an association between CPG and instrumental delivery and cesarean section. (AU)

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

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

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

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

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