Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis.

Lupus nephritis is a leading cause of mortality among systemic lupus erythematosus (SLE) patients, and its heterogeneous nature poses a significant challenge to the development of effective diagnostics and treatments. Single cell RNA sequencing (scRNA-seq) offers a potential solution to dissect the heterogeneity of the disease and enables the study of similar cell types distant from the site of renal injury to identify novel biomarkers. We applied scRNA-seq to human renal and skin biopsy tissues and demonstrated that scRNA-seq can be performed on samples obtained during routine care. Chronicity index, IgG deposition, and quantity of proteinuria correlated with a transcriptomic-based score composed of IFN-inducible genes in renal tubular cells. Furthermore, analysis of cumulative expression profiles of single cell keratinocytes dissociated from nonlesional, non-sun-exposed skin of patients with lupus nephritis also revealed upregulation of IFN-inducible genes compared with keratinocytes isolated from healthy controls. This indicates the possible use of scRNA-seq analysis of skin biopsies as a biomarker of renal disease. These data support the potential utility of scRNA-seq to provide new insights into the pathogenesis of lupus nephritis and pave the way for exploiting a readily accessible tissue to reflect injury in the kidney.

[The X of dyslipemias]. / La X de las dislipemias.

Patients with cholestatic diseases can present secondary hypercholesterolemia, as a result of the accumulation of lipoprotein X (Lp-X); an abnormal LDL form, considered as the biochemical parameter more sensitive and specific for the diagnosis of cholestasis intra or extrahepatic cholestasis. The aim of this clinical communication is to illustrate this association. A 54-year-old male with severe cholestatic liver disease which in turn presents a progressive total cholesterol rise and LDL with presence of lipoprotein X. Total and LDL cholesterol were down to normal, also coinciding with the improvement of cholestatic liver disease conferring cardiovascular protection pattern.

Los pacientes con colestasis hepática pueden presentar hipercolesterolemia secundaria, como consecuencia de la acumulación de la lipoproteína X (Lp-X); una forma anómala de LDL, considerada como el parámetro bioquímico más sensible y específico para el diagnóstico de colestasis intra o extrahepática. El objetivo de esta comunicación clínica es ilustrar esta asociación. Se trata de un varón de 54 años con hepatopatía colestásica severa que a su vez presenta una elevación progresiva de colesterol total y LDL con presencia de lipoproteína X. El colesterol total y LDL, descendieron progresivamente hasta normalizarse, coincidiendo con la mejoría de la función hepática, confiriendo un patrón de protección cardiovascular.

Hyperuricemia and metabolic syndrome in children with overweight and obesity

Objetivo: Estudiar la prevalencia de hiperuricemia en niños con sobrepeso u obesidad y analizarla relación con el síndrome metabólico y las enfermedades que lo definen. Materiales y métodos: Se realizó un estudio de prevalencia transversal en 148 niños con sobrepeso u obesidad (12 ± 3 años, 48% chicos, IMC 31,8 ± 6,1) reclutados de una consulta de endocrinología pediátrica. Se determinaron el IMC, la cintura-talla, el perímetro de la cintura, la presión arterial con el equipo habitual y la glucosa (en ayunas y tras sobrecarga con 75 g), la resistencia a la insulina, el colesterol HDL, los triglicéridos y el ácido úrico. Resultados: La prevalencia de hiperuricemia era del 53%. Los pacientes con hiperuricemia tenían valores superiores de IMC (33,9 frente a 30,6; p = 0,003), perímetro de cintura (101,4frente a 91,1 cm; p < 0,001) y presión arterial sistólica (123,4 frente a 111,9 mmHg; p < 0,001)y diastólica (78,2 frente a 68,7 mmHg; p < 0,001). Mostraban además una glucemia más alta después de la sobrecarga oral de glucosa (107,5 frente a 100,7 mg/dl; p = 0,03), valores superiores de insulina (29,2 frente a 20,7 mg/dl; p = 0,001) y HOMA IR (6,5 frente a 4,4; p < 0,001) y concentraciones más bajas de HDL (49,5 frente a 54,4 mg/dl; p = 0,02).El valor de ácido úrico correspondiente con mayor probabilidad al diagnóstico de síndrome metabólico en nuestra muestra era de 5,4 mg/dl (sensibilidad del 64% y especificidad del 62%).Conclusión: La prevalencia de hiperuricemia en niños con sobrepeso y obesidad es alta. En el grupo de pacientes con obesidad e hiperuricemia hallamos que los parámetros determinados para diagnosticar el síndrome metabólico eran menos favorables. La concentración de ácido úrico a partir de la cual existe una mayor posibilidad de encontrar síndrome metabólico es de5,4 mg/dl (AU)

Objective: To study the prevalence of hyperuricemia in children with overweight or obesity and analyze the relation with metabolic syndrome and the diseases that define it. Materials and methods This is a cross-sectional prevalence study in 148 children recruited from pediatric endocrinology consultation, with overweight or obesity (12±3 years, 48% boys, BMI 31.8±6.1). We measured BMI, waist-height, waist circumference, blood pressure with standard instrumentation and glucose (fasting and after overload with 75g), insulin resistance, cholesterol HDL, triglycerides and uric acid. Results The prevalence of hyperuricemia was 53%. Patients with hyperuricemia had greater BMI (33.9 vs 30.6, p=0.003), plus waist circumference (101.4 vs 91.1cm, p<0.001), higher blood pressure: systolic (123.4 vs 111.9mm Hg, p<0.001), diastolic (78.2 vs 68.7mm Hg, p<0.001). They presented greater blood glucose after overload oral glucose (107.5 vs 100.7mg/dl, p=0.03), insulin was higher (29.2 vs 20.7mg/dl, p=0.001) as well as HOMA IR (6.5 vs 4.4, p<0.001) and HDL levels were lower (49.5 vs 54.4mg/dl, p=0.02).Uric acid's level which most is the likely diagnosis of metabolic syndrome corresponds to 5.4mg/dl in our sample (sensitivity: 64% and specificity 62%).Conclusion The prevalence of hyperuricemia in children with overweight and obesity is high. In the group of patients with obesity and hyperuricemia, we found out that the parameters measured to diagnose with metabolic syndrome were less favorable. Uric acid's level from where there is a higher possibility to see metabolic syndrome is 5.4mg/dl (AU)

Hyperuricemia and metabolic syndrome in children with overweight and obesity.

OBJECTIVE: To study the prevalence of hyperuricemia in children with overweight or obesity and analyze the relation with metabolic syndrome and the diseases that define it. MATERIALS AND METHODS: This is a cross-sectional prevalence study in 148 children recruited from pediatric endocrinology consultation, with overweight or obesity (12±3 years, 48% boys, BMI 31.8±6.1). We measured BMI, waist-height, waist circumference, blood pressure with standard instrumentation and glucose (fasting and after overload with 75 g), insulin resistance, cholesterol HDL, triglycerides and uric acid. RESULTS: The prevalence of hyperuricemia was 53%. Patients with hyperuricemia had greater BMI (33.9 vs 30.6, p=0.003), plus waist circumference (101.4 vs 91.1cm, p<0.001), higher blood pressure: systolic (123.4 vs 111.9 mm Hg, p<0.001), diastolic (78.2 vs 68.7 mm Hg, p<0.001). They presented greater blood glucose after overload oral glucose (107.5 vs 100.7 mg/dl, p=0.03), insulin was higher (29.2 vs 20.7 mg/dl, p=0.001) as well as HOMA IR (6.5 vs 4.4, p<0.001) and HDL levels were lower (49.5 vs 54.4 mg/dl, p=0.02). Uric acid's level which most is the likely diagnosis of metabolic syndrome corresponds to 5.4 mg/dl in our sample (sensitivity: 64% and specificity 62%). CONCLUSION: The prevalence of hyperuricemia in children with overweight and obesity is high. In the group of patients with obesity and hyperuricemia, we found out that the parameters measured to diagnose with metabolic syndrome were less favorable. Uric acid's level from where there is a higher possibility to see metabolic syndrome is 5.4 mg/dl.

[Prevalence of carbohydrate metabolism disturbances in a population of children and adolescents with severe obesity]. / Prevalencia de alteraciones del metabolismo hidrocarbonado en una población infanto-juvenil con obesidad grave.

INTRODUCTION: There is currently a disproportionate increase in childhood and adolescent obesity worldwide, together with other disorders involving substantial cardiometabolic risk in adulthood, such as alterations in carbohydrate metabolism. OBJECTIVE: To establish the prevalence of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) after an oral glucose tolerance test, and the prevalence of type 2 diabetes mellitus (DM-2) in a pediatric population with severe obesity. Additionally, we aimed to assess clinical metabolic differences between prediabetic obese patients and obese subjects without prediabetes. MATERIAL AND METHODS: A cross-sectional study was carried out in children and adolescents with severe obesity (>97th percentile). The variables studied were age, sex, height, weight, body mass index, waist circumference, fasting plasma glucose and oral glucose tolerance test, insulinemia, insulin resistance assessed by the homeostasis model assessment (HOMA) index, glycated hemoglobin (HbA(1c)), triglycerides, high-density lipoprotein cholesterol (HDL), and systolic and diastolic blood pressure. RESULTS: A total of 133 patients were included: 67 boys (50.4%) and 66 girls (49.6%), with a mean age of 12.17±3.27 years. Fourteen patients (10.52%) had prediabetes (10 IFG, 3 IGT, 1 IFG+IGT): 7 girls and 8 boys, with a mean age of 13.2±3.3 years. One patient had DM2 (0.75%). Patients with prediabetes had significantly higher concentrations of fasting glucose (98±10.76 vs 88.53±6.3mg/d; p=0.001), insulinemia (35.38±14.22 vs 22.95±14.30µU/ml; p=0.009) and HOMA index (8.10±3.24 vs 4.89±3.27; p=0.004) than patients without impaired carbohydrate metabolism. These patients also had higher values of HbA(1c), triglycerides, blood pressure and HDL concentrations, although differences were not statistically significant. CONCLUSIONS: The prevalence of prediabetes (IFG/IGT) in children with severe obesity was high (10.52%). These patients should therefore be investigated to establish early diagnosis and appropriate treatment. Obese patients with prediabetes have significantly higher levels of insulin and insulin resistance than individuals without impaired carbohydrate metabolism.

Revisión casuística en el hospital universitario de Getafe de pacientes con patología hipofisaria adenomatosa intervenidos quirúrgicamente / Casuistry review of patients undergoing surgery for pituitary adenomas in Getafe University Hospital (Spain)

Objetivo Revisión casuística de pacientes diagnosticados de adenomas hipofisarios (AH) que han sido intervenidos en nuestro centro desde el año 1995 por el mismo neurocirujano. Material y métodos Estudio retrospectivo descriptivo de 98 pacientes intervenidos por AH entre 1995–2008. Se analizó tamaño tumoral, datos de funcionalidad, anatomía patológica y complicaciones posquirúrgicas. La distribución de los datos se hizo atendiendo a la fecha de cirugía en 2 grupos: 1995–2002 (1.er periodo) y 2003–2008 (2.° periodo).Resultados Se realizaron 110 intervenciones quirúrgicas. En el 1.er periodo tuvieron lugar 59 intervenciones y en el 2.° se realizaron 51. De estas, 49 fueron AH no funcionantes y 61 funcionantes. Se hallaron 85 macroadenomas y 25 microadenomas. Resultados Del total de macroadenomas, la curación se obtuvo en 31 pacientes (36%) frente a 21 (84%) en de los microadenomas. P<0,05. El número de complicaciones fue significativamente mayor en el 1.er periodo; 32 pacientes (54%) frente a 16 pacientes en el 2.° periodo (31,3%). P<0,05. En el 1.er periodo se curaron 28 pacientes (47,4%) y en el segundo 31 (52,1%). P=0,1. Tasa de mortalidad: 0,9%.ConclusionesLa tasa de curación de microadenomas es significativamente superior a la de macroadenomas como ya se describe en trabajos previos. Se evidencia de manera significativa una menor incidencia de complicaciones quirúrgicas y una tendencia al aumento del porcentaje de curación global en el 2.° periodo del estudio. Estos resultados probablemente estén en relación con el aumento de la experiencia del neurocirujano debido a la adquisición de destreza quirúrgica (AU)

Objective To perform a casuistry review of patients diagnosed with pituitary adenomas (PA) who underwent surgery performed by the same neurosurgeon after 1995.Material and methods A descriptive and retrospective study was performed in 98 patients with PA undergoing surgery from 1995–2008. Tumor size and data on functionality, pathology and postprocedural complications were analyzed. The study was divided into two periods: 1995–2002 (first period) and 2003–2008 (second period).Results A total of 110 surgical interventions (59 in the first period and 51 in the second) were performed for 49 non-hormone-producing PA and 61 hormone-producing PA. There were 85 macroadenomas and 25 microadenomas. Cure was achieved in 31 patients (36%) with macroadenomas and in 21 patients (84%) with microadenomas (P=0.05).The number of complications was significantly higher in the first period [32 patients (54 %)] than in the second period [16 patients (31.3%)] (P<0.05). Cure was achieved in 28 patients (47.4%) in the first period compared with 31 (52.1%) in the second (P=0.1). The mortality rate was 0.9%.ConclusionsAs described in previous studies, the cure rate was significantly higher for microadenomas than for macroadenomas. There was a significant reduction in the incidence of surgical complications and a trend toward an increase in the percentage of overall healing in the second period of the study. These results are probably related to the neurosurgeon's greater experience and surgical skill (AU)

[Casuistry review of patients undergoing surgery for pituitary adenomas in Getafe University Hospital (Spain)]. / Revisión casuística en el hospital universitario de Getafe de pacientes con patología hipofisaria adenomatosa intervenidos quirúrgicamente.

OBJECTIVE: To perform a casuistry review of patients diagnosed with pituitary adenomas (PA) who underwent surgery performed by the same neurosurgeon after 1995. MATERIAL AND METHODS: A descriptive and retrospective study was performed in 98 patients with PA undergoing surgery from 1995-2008. Tumor size and data on functionality, pathology and postprocedural complications were analyzed. The study was divided into two periods: 1995-2002 (first period) and 2003-2008 (second period). RESULTS: A total of 110 surgical interventions (59 in the first period and 51 in the second) were performed for 49 non-hormone-producing PA and 61 hormone-producing PA. There were 85 macroadenomas and 25 microadenomas. Cure was achieved in 31 patients (36%) with macroadenomas and in 21 patients (84%) with microadenomas (P=0.05).The number of complications was significantly higher in the first period [32 patients (54 %)] than in the second period [16 patients (31.3%)] (P<0.05). Cure was achieved in 28 patients (47.4%) in the first period compared with 31 (52.1%) in the second (P=0.1). The mortality rate was 0.9%. CONCLUSIONS: As described in previous studies, the cure rate was significantly higher for microadenomas than for macroadenomas. There was a significant reduction in the incidence of surgical complications and a trend toward an increase in the percentage of overall healing in the second period of the study. These results are probably related to the neurosurgeon's greater experience and surgical skill.