Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes / El tratamiento intensivo precoz mejora los resultados en pacientes con hiperfiltración glomerular y diabetes tipo 2

Background and objective: Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors. Patients and methods: This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2 ± 6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using 125I-iothalamate. Results: There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were −1.55 mL/min/1.73 m2/year in patients with stable creatinine, −2.49 mL/min/1.73 m2/year in those with doubled creatinine, and −8.16 mL/min/1.73 m2/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment. Conclusion: Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function (AU)

Antecedentes y objetivo: Aproximadamente el 24-40% de los pacientes con diabetes mellitus tipo 2 (DM2) desarrollan daño renal. Nuestro objetivo fue evaluar la evolución a largo plazo de la función renal mediante la determinación isotópica del filtrado glomerular (FG) y la excreción urinaria de albúmina (EUA) en pacientes con DM2 en tratamiento intensivo de los factores de riesgo renal y cardiovascular. Pacientes y métodos: Estudio prospectivo unicéntrico de 201 pacientes con DM2 y EUA que iniciaron un tratamiento intensivo. El seguimiento fue de 17,2 ± 6,5 años. Los pacientes fueron divididos en 3 grupos según la función renal al final: 167 (85,6%) tenían función renal estable, 16 (8,2%) doblaron la creatinina y 12 (6,2%) requirieron tratamiento renal sustitutivo (TRS). Se realizaron determinaciones isotópicas periódicas del FG usando 125I-iotalamato. Resultados: Hay diferencias significativas entre los 3 grupos respecto a la edad, los años de duración de la DM2 al inicio, los años de seguimiento, la presión arterial sistólica, la creatinina sérica, el FG isotópico y la EUA basal. Las pendientes de evolución de la función renal fueron: −1,55 ml/min/1,73 m2/año en pacientes estables, −2,49 ml/min/1,73 m2/año en los que doblaron la creatinina y −8,16 ml/min/1,73 m2/año en los que requirieron TRS. Además, esta diferente evolución de la función renal venía determinada por el inicio tardío del tratamiento intensivo. Conclusión: Los pacientes con hiperfiltración glomerular en tratamiento con bloqueadores del sistema renina-angiotensina-aldosterona mostraron una mejor evolución de la función renal, posiblemente debido a que estos pacientes iniciaron tratamiento intensivo antes. Aunque la nefropatía diabética se asocia a factores de riesgo clásicos, el tratamiento intensivo precoz debe ser una prioridad con el fin de prevenir el deterioro de la función renal (AU)

Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes.

BACKGROUND AND OBJECTIVE: Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors. PATIENTS AND METHODS: This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2±6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using (125)I-iothalamate. RESULTS: There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were -1.55mL/min/1.73m(2)/year in patients with stable creatinine, -2.49mL/min/1.73m(2)/year in those with doubled creatinine, and -8.16mL/min/1.73m(2)/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment. CONCLUSION: Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function.

Impacto asistencial tras la introducción de la ecografía tiroidea en una unidad monográfica de atención al nódulo tiroideo / Healthcare impact of introduction of thyroid ultrasound in a thyroid nodule pathology unit

Introducción La incidencia de cáncer de tiroides ha aumentado en las últimas décadas en todo el mundo. Objetivo Aportar evidencias sobre la eficiencia diagnóstica y asistencial si la atención al nódulo tiroideo se realiza en una consulta monográfica que integre exploración clínica, estudio ecográfico y citología con valoración in situ. Pacientes y métodos Pacientes que acudieron a la consulta monográfica de nódulo tiroideo entre enero 2004 y junio 2010. Basado en la disposición del ecógrafo en el momento de la visita 2 períodos son definidos: primer periodo (P1: 01/2004-09/2007) sin ecógrafo en la consulta, PAAF por palpación; y segundo periodo (P2: 10/2007-06/2010) con ecógrafo, PAAF eco-guiada. Resultados Un total de 1.036 pacientes [P1: 537 (52%), P2: 499 (48%)] fueron consultados e incluidos. Eficiencia diagnóstica (P1 vs P2): número de pacientes visitados/año fue 143 vs 181, p<0,001; número de PAAF/nódulo: 1,68 vs 1,17, p<0,001; porcentaje de PAAF con material insuficiente: 26 vs 5,3%, p<0,001; tamaño medio (DE) del nódulo: 23,6 (12,4) vs 21,7 (11,7) mm, p 0,040; porcentaje de nódulos estudiados menores a 10mm: 9,9 vs 13,7%, p 0,030.Eficiencia asistencial: tiempo medio (rango) entre primera visita e indicación de cirugía: 332 (0-2177) vs 108 (0-596) días, p<0,001; relación de pacientes derivados a cirugía por sospecha citológica/por otros motivos: 1,06 vs 2,21, p<0,001; y de neoplasia/patología benigna intervenida: 0,47 vs 0,93, p=0,002.ConclusiónLa consulta monográfica del nódulo tiroideo, que integra exploración clínica, ecografía y citología con valoración in situ, aumenta la eficiencia diagnóstica y asistencial del nódulo tiroideo (AU)

Introduction: Worldwide incidence of thyroid cancer has increased in recent decades. Objective: To provide evidence of the diagnostic and care efficiency of a monographic thyroid nodule clinic integrating clinical examination, ultrasound examination, and cytology with onsite evaluation. Patients and methods: Patients attending the monographic thyroid nodule clinic from January2004 to June 2010. Two periods may be distinguished based on availability of ultrasound equipment at the time of the (..) (AU)

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

CONTEXT: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. OBJECTIVE: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). RESULTS: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.

[Healthcare impact of introduction of thyroid ultrasound in a thyroid nodule pathology unit]. / Impacto asistencial tras la introducción de la ecografía tiroidea en una unidad monográfica de atención al nódulo tiroideo.

INTRODUCTION: Worldwide incidence of thyroid cancer has increased in recent decades. OBJECTIVE: To provide evidence of the diagnostic and care efficiency of a monographic thyroid nodule clinic integrating clinical examination, ultrasound examination, and cytology with on site evaluation. PATIENTS AND METHODS: Patients attending the monographic thyroid nodule clinic from January 2004 to June 2010. Two periods may be distinguished based on availability of ultrasound equipment at the time of the visit: a first period (P1: 01/2004-09/2007) where no ultrasound equipment was available at the clinic and FNA by palpation was performed, and a second period (P2: 10/2007-06/2010) where this equipment was available and ultrasound-guided FNA was performed. RESULTS: A total of 1036 patients [P1: 537 (52%), P2: 499 (48%)] were seen and enrolled. Diagnostic efficiency (P1 vs P2): 143 vs 181 patients were seen annually, p<0.001; FNA number/nodule: 1.68 vs 1.17, p<0.001; percent FNAs with inadequate material: 26% vs 5.3%, p<0.001; mean (SD) nodule size: 23.6 (12.4) vs 21.7 (11.7) mm, p 0.040; proportion of nodules examined less than 10mm in size: 9.9% vs 13.7%, p 0.030. Care efficiency: mean time (range) from the first visit to surgery indication: 332 (0-2177) vs 108 (0-596) days, p<0.001; proportion of patients referred for surgery due to suspect cytology/other reasons: 1.06 vs 2.21, p<0.001; and operated benign neoplasm/pathology: 0.47 vs 0.93, p=0.002. CONCLUSION: A monographic thyroid nodule clinic integrating clinical examination, ultrasound, and cytology evaluated on site increases diagnostic and care efficiency in patients with thyroid nodules.

Pregnancy-associated plasma protein-A is related to gender and to adipocytokine levels: results of the Health Survey of Catalonia.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. AIM: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. DESIGN AND METHODS: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. RESULTS: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) µIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (ß = 0·23; P = 0·02) and leptin (ß = -0·33; P = 0·04). CONCLUSIONS: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined.

Ausencia de detección de ADN de Chlamydophila pneumoniae en leucocitos de pacientes diabéticos tipo 2 con aterosclerosis carotídea y sin ella / Non-detectable Chlamydophila pneumoniae DNA in peripheral leukocytes in type 2 diabetes mellitus patients with and without carotid atherosclerosis

Fundamento y objetivo: En un estudio transversal, se evaluó la presencia de ADN de Chlamydophila pneumoniae (ADN-CP) en leucocitos de sangre periférica mediante reacción en cadena de la polimerasa (PCR) en tiempo real en pacientes con diabetes mellitus tipo 2 (DM2) y diferentes grados de aterosclerosis carotídea.Pacientes y método: Se incluyeron 135 pacientes con DM2. Se determinaron variables clínicas, metabólicas e inflamatorias. Se registraron los antecedentes de enfermedad macrovascular clínica, se realizó ecografía carotídea y PCR en tiempo real para el ADN-CP.Resultados: La edad fue de 62 (7) años. La duración de la diabetes fue de 16 (9) años. El 40,7% de los pacientes presentaban aterosclerosis clínica, el 32,5% aterosclerosis subclínica y el 26,6% no evidencia de aterosclerosis. Todos los grupos fueron homogéneos en los datos antropométricos. Los pacientes con aterosclerosis clínica tenían mayor grosor de la íntima-media carotídea en comparación con los otros dos grupos. No se detectó ADN-CP en ninguno de los casos estudiados.Conclusiones: La falta de detección de ADN-CP en leucocitos de sangre periférica sugiere que esta bacteria no parece tener un papel activo sistémico en la patogénesis de la aterosclerosis en pacientes con DM2 y no sería un marcador fiable de aterosclerosis en pacientes de alto riesgo (AU)

Background and objective: To study Chlamydophila pneumoniae DNA (CP-DNA) in leukocytes measured by real-time polymerase chain reaction (PCR) in patients with type 2 diabetes mellitus (DM2) with different degrees of atherosclerosis, a cross-sectional protocol was performed.Patients and methods: We included 135 patients with DM2. Clinical, metabolic and inflammatory variables were measured. Previous clinical macrovascular disease was recorded and carotid ultrasound and real-time PCR for CP-DNA were performed. Results: Mean age was 62 (7) years and mean diabetes duration 16 (9) years; 40.7% of patients presented clinical atherosclerosis, 32.5% subclinical atherosclerosis and 26.6% no evidence of atherosclerosis. Anthropometric data were homogeneous in the three groups. Patients with clinical atherosclerosis had greater carotid intima-media thickness compared to the other two groups. No CP-DNA was detected in any patient.Conclusions: The lack of detection of CP-DNA in blood leukocytes suggests that C. pneumoniae plays no active, systemic role in the pathogenesis of atherosclerosis in DM2 patients and is not a reliable marker of atherosclerosis in high-risk patients (AU)

Non-detectable Chlamydophila pneumoniae DNA in peripheral leukocytes in type 2 diabetes mellitus patients with and without carotid atherosclerosis.

BACKGROUND AND OBJECTIVE: To study Chlamydophila pneumoniae DNA (CP-DNA) in leukocytes measured by real-time polymerase chain reaction (PCR) in patients with type 2 diabetes mellitus (DM2) with different degrees of atherosclerosis, a cross-sectional protocol was performed. PATIENTS AND METHODS: We included 135 patients with DM2. Clinical, metabolic and inflammatory variables were measured. Previous clinical macrovascular disease was recorded and carotid ultrasound and real-time PCR for CP-DNA were performed. RESULTS: Mean age was 62 (7) years and mean diabetes duration 16 (9) years; 40.7% of patients presented clinical atherosclerosis, 32.5% subclinical atherosclerosis and 26.6% no evidence of atherosclerosis. Anthropometric data were homogeneous in the three groups. Patients with clinical atherosclerosis had greater carotid intima-media thickness compared to the other two groups. No CP-DNA was detected in any patient. CONCLUSIONS: The lack of detection of CP-DNA in blood leukocytes suggests that C. pneumoniae plays no active, systemic role in the pathogenesis of atherosclerosis in DM2 patients and is not a reliable marker of atherosclerosis in high-risk patients.

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon-induced thyroiditis.

OBJECTIVE: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT. DESIGN, PATIENTS AND METHODS: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT). RESULTS: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV. CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.

Bone mineral density and bone fracture in male patients receiving long-term suppressive levothyroxine treatment for differentiated thyroid carcinoma.

Studies on the effect of exogenous subclinical thyrotoxicosis on bone mineral density (BMD) in male patients treated with suppressive doses of levothyroxine for differentiated thyroid carcinoma (DTC) are not conclusive. In order to evaluate BMD (in femoral neck, lumbar spine, and distal radius) and bone fractures in men under long-term suppressive treatment with levothyroxine for DTC, we conducted a cross-sectional, retrospective study in 33 Caucasian men (mean ± SD age: 56 ± 14 years) under treatment for DTC. The control group comprised 33 healthy age- and body mass index-matched male volunteers. BMD was assessed by dual-energy X-ray absorptiometry (DXA). Bone turnover biomarkers (calcium, phosphate, alkaline phosphatase, PTH, vitamin D, urinary calcium, and N-Telopeptide/creatinine index) and testosterone were determined. Previous bone fractures were evaluated with a questionnaire and X-ray images of thoracic and lumbar vertebrae. Patients were treated for a mean duration of 15 ± 5 years. No differences were found between patients and controls in bone turnover biomarkers or areal BMD, T-scores or Z-scores in all sites evaluated. No earlier fractures or pain episodes were registered in either group and the incidence of asymptomatic vertebral fractures did not differ significantly between patient (18.8%) and control groups (16.7%), (P = 0.9). In conclusion, long-term suppressive treatment with levothyroxine in men with DTC does not appear to exert deleterious effects on bone mineral density or increase the prevalence of fracture.

Percepción de los endocrinólogos clínicos sobre los potenciales efectos perjudiciales del tratamiento supresor de la TSH en el carcinoma diferenciado de tiroides / Clinical endocrinologists’ perception of the deleterious effects of TSH suppressive therapy in patients with differentiated thyroid carcinoma

Objetivo Conocer la opinión de un grupo endocrinólogos sobre los potenciales efectos perjudiciales del tratamiento supresor (TS) en el carcinoma diferenciado de tiroides (CDT).Material y métodos Encuesta a un grupo de endocrinólogos con experiencia en el tratamiento del CDT. El cuestionario constaba de 3 preguntas: la primera respecto a los posibles efectos adversos sobre diferentes órganos y sistemas, la segunda sobre la trascendencia clínica de los mismos y la tercera sobre la utilidad de las guías de tratamiento del CDT. Resultados Respondieron 91 endocrinólogos con una gran discrepancia de opiniones. Ninguna pregunta tuvo más del 80% de respuestas en un determinado sentido. De los posibles efectos indeseables del TS, en 3 de ellos (aumento de la masa ventricular izquierda, la taquicardia de reentrada y la disfunción diastólica) se reconoció un elevado grado de desconocimiento, en 7 (demencia, disminución de la calidad de vida, enfermedad tromboembólica, disminución de la densidad mineral ósea en mujeres premenopáusicas y varones, signos y síntomas de hipertiroidismo y aumento del riesgo de fracturas), la mayoría de los encuestados consideraron que no se afectaban por el TS, mientras que en 2 (aumento de la frecuencia cardiaca y disminución de la densidad mineral ósea en mujeres postmenopáusicas), la mayoría respondieron afirmativamente. El 80% de los encuestados consideró que estos efectos no tenían trascendencia clínica. Respecto a las guías de tratamiento, un 33% opinó que deberían ser revisadas. Conclusione sLa percepción de los endocrinólogos sobre los potenciales efectos perjudiciales del tratamiento supresor en el CDT es muy heterogénea (AU)

Objective To explore the opinion of clinical endocrinologists as to the deleterious effects of thyrotropin (TSH) suppressive therapy in patients with differentiated thyroid carcinoma (DTC).Materials and methods A self-administered survey was sent by e-mail to a group of endocrinologists with expertise in the treatment of patients with differentiated thyroid carcinoma. The questionnaire consisted of three questions related to: 1) the possible adverse effects of this therapy on different organ systems, 2) the clinical significance of these effects and 3) the usefulness of treatment guidelines for DTC. Results A total of 91 endocrinologists responded with a wide divergence of opinions. No question had more than 80% of answers in a particular option. Of the possible side effects of suppressive therapy, a high degree of ignorance to three of them (increased left ventricular mass, reentrant tachycardia and diastolic dysfunction). Most respondents felt that the seven items, dementia and Alzheimer, decreased quality of life, decreased bone mineral density (BMD) in premenopausal women and men, thromboembolic disease, signs and symptoms of hyperthyroidism and increased risk of fractures were not affected by suppressive therapy, while most responded positively to two items (increased heart rate and decreased BMD in postmenopausal women). Eighty percent of the respondents felt that in any case these effects were not clinically significant and 33% considered that treatment guidelines should be reviewed. Conclusions Clinical endocrinologists seem to have a very heterogeneous opinion regarding the potential harmful effects of TSH-suppressive therapy for DTC (AU)

Estudio comparativo de las series históricas de carcinoma diferenciado de tiroides en dos centros hospitalarios de tercer nivel españoles en relación a series norteamericanas / Comparative study of historical series of differentiated thyroid carcinoma in two tertiary hospitals in Spain versus north American series

Antecedentes y objetivo Existe escasa literatura nacional de series descriptivas de pacientes con carcinoma diferenciado de tiroides (CDT) y seguimiento a largo plazo en España. El objetivo de nuestro estudio ha sido describir las series de CDT de dos hospitales de tercer nivel (Hospital Clínic de Barcelona [HC] i Hospital Germans Trias i Pujol de Badalona [HGTiP]) y compararlas con las descritas en la National Cancer Data Base (NCDB), y la Clínica Mayo (CM), las series internacionales más destacadas por número de pacientes y tiempo de seguimiento. Material y método Estudio retrospectivo de revisión de historias clínicas de pacientes diagnosticados de CDT en dos hospitales de tercer nivel del área de Barcelona. Revisión y comparación con los resultados publicados por la NCDB y la CM. Resultados Se revisaron 480 historias clínicas de pacientes con CDT diagnosticados entre 1973 y 2006 y con un tiempo de seguimiento de 16±8 años. No hubo diferencias significativas entre la serie conjunta HC/HGTiP y la NCDB respecto a las características clínicas, los factores de riesgo y la forma de presentación más frecuente. La ecografía y la citología fueron los métodos diagnósticos más utilizados en todas las series y el principal tipo de cirugía fue una tiroidectomía total o casi total, sin diferencias entre los grupos estudiados. Se administró con más frecuencia tratamiento postoperatorio con i131 en la serie HC/HGTiP (83,9%) que en la de la NCDB (55,1%) o la CM (46%). En los pacientes de la serie conjunta la recidiva tumoral fue del 9,3% y la mortalidad específica del 1,8%.Conclusiones Las series del HC y HGTiP fueron comparables entre sí con similitud de las diferentes técnicas diagnósticas y terapéuticas. El estudio pone en evidencia evolución histórica respecto al uso de exploraciones de imagen, y diferencias respecto a las grandes series americanas referentes a ciertas exploraciones (p.ej. laringoscopia) o al uso de tratamiento ablativo con i131 (AU)

Background and objective There is little national literature on descriptive series of patients with differentiated thyroid carcinoma (DTC) and long-term monitoring in Spain. The aim of our study was to describe the DTC series in two tertiary hospitals [Hospital Clínic de Barcelona (HC) and Hospital Germans Trias i Pujol (HGTiP)] and compare these series with those described in the National Cancer Data Base (NCDB) and the Mayo Clinic, the leading international series by number of patients and length of follow-up.Material and methods We performed a retrospective review of the medical records of patients diagnosed with DTC in two tertiary hospitals in the Barcelona area. The results were compared with those published by the NCDB and the Mayo Clinic.Results We reviewed 480 medical records of patients with DTC diagnosed between 1973 and 2006, with a mean follow-up of 16±8 years. No significant differences were observed in clinical characteristics, risk factors or the most frequent form of presentation between the joint HC/HGTiP group and the NCDB series. The most commonly used diagnostic methods were ultrasound and cytology in all series and the main type of surgery was total or nearly total thyroidectomy, with no differences between groups. Postoperative I-131 was administered more often in the HC/HGTiP series (83.9%) than in the NCDB series (55.1%) and in the Mayo Clinic (46%). In the HC/HGTiP group tumor recurrence was 9.3% and mortality 1.8%.Conclusions The HC and HGTiP series were comparable and the various diagnostic and therapeutic techniques used were similar. This study highlights historical trends in the use of imaging techniques, as well as differences with large American series in some procedures (such as laryngoscopy) and the use of radioiodine therapy (AU)

[Comparative study of historical series of differentiated thyroid carcinoma in two tertiary hospitals in Spain versus North American series]. / Estudio comparativo de las series históricas de carcinoma diferenciado de tiroides en dos centros hospitalarios de tercer nivel españoles en relación a series norteamericanas.

BACKGROUND AND OBJECTIVE: There is little national literature on descriptive series of patients with differentiated thyroid carcinoma (DTC) and long-term monitoring in Spain. The aim of our study was to describe the DTC series in two tertiary hospitals [Hospital Clínic de Barcelona (HC) and Hospital Germans Trias i Pujol (HGTiP)] and compare these series with those described in the National Cancer Data Base (NCDB) and the Mayo Clinic, the leading international series by number of patients and length of follow-up. MATERIAL AND METHODS: We performed a retrospective review of the medical records of patients diagnosed with DTC in two tertiary hospitals in the Barcelona area. The results were compared with those published by the NCDB and the Mayo Clinic. RESULTS: We reviewed 480 medical records of patients with DTC diagnosed between 1973 and 2006, with a mean follow-up of 16±8 years. No significant differences were observed in clinical characteristics, risk factors or the most frequent form of presentation between the joint HC/HGTiP group and the NCDB series. The most commonly used diagnostic methods were ultrasound and cytology in all series and the main type of surgery was total or nearly total thyroidectomy, with no differences between groups. Postoperative I-131 was administered more often in the HC/HGTiP series (83.9%) than in the NCDB series (55.1%) and in the Mayo Clinic (46%). In the HC/HGTiP group tumor recurrence was 9.3% and mortality 1.8%. CONCLUSIONS: The HC and HGTiP series were comparable and the various diagnostic and therapeutic techniques used were similar. This study highlights historical trends in the use of imaging techniques, as well as differences with large American series in some procedures (such as laryngoscopy) and the use of radioiodine therapy.

Utilidad de la pulsioximetría en el cribado de la aterosclerosis carotídea en pacientes con diabetes mellitus tipo 2 / Usefulness of pulse oximetry in screening of carotid atherosclerosis in patients with type 2 diabetes mellitus

Fundamento y objetivo: La pulsioximetría se ha propuesto como método de cribado de la vasculopatía periférica. Dado que la arteriosclerosis afecta a todo el territorio vascular, estudiamos su eficacia para detectar pacientes con diabetes mellitus tipo 2 (DM2) con arteriosclerosis carotídea.Pacientes y método: Se incluyeron 105 pacientes con DM2 sin historia previa de vasculopatía periférica. Se realizó historia clínica, exploración física, medición del índice tobillo-brazo (ITB) y de la saturación de oxígeno en el pie y la mano mediante pulsioximetría, análisis sanguineo y ecografía carotídea (medición del grosor íntima-media carotídeo y de placas carotídeas [PC]). Se consideraron patológicos los valores de ITB inferiores a 0,9 y un descenso en la pulsioximetría de la saturación de oxígeno superior al 2% en los pies respecto de la mano o tras la elevación de la extremidad inferior respecto del decúbito supino. Resultados: Sesenta pacientes eran varones (edad media de 62,1 años [desviación estándar de 7,1] y hemoglobina glucosilada media del 6,9% [1,0]). Un 58,1% presentaba PC. Los datos antropométricos y analíticos fueron homogéneos entre los pacientes con y sin PC. El ITB fue inferior a 0,9 en el 49% y en el 25% de los pacientes con y sin PC, respectivamente. No hubo diferencias en la pulsioximetría en función de la presencia de PC ni del ITB patológico. Tampoco el grosor íntima-media fue diferente en función de la pulsioximetría, aunque fue mayor en los pacientes con PC y con ITB inferior a 0,9 que en aquéllos sin alteraciones. Estos resultados fueron independientes de la historia de macroangiopatía clínica (AU)

Background and objective: Pulse oximetry of the toes has been suggested in the screening of peripheral arterial disease. We studied the uselfuness of pulse oximetry in detection of type 2 diabetic patients with carotid atherosclerosis. Subjects and methods: 105 patients with type 2 diabetes mellitus (DM) without previous clinical peripheral arterial disease were enrolled. All patients had (1) ankle-brachial index (ABI) measurement, (2) pulse oximetry to measure SaO2 of their index fingers and big toes in the supine position and at elevated 30cm and (3) a carotid ultrasound [carotid artery intima-media thickness (IMT) and carotid plaques (CP) measurements]. The ABI was considered abnormal when it was <0.9 and when the pulse oximetry showed a decrease in SaO2 of >2% of the finger compared to foot or to 30cm foot elevation. Results: 60 patients were men (age of 62±7 years, HbA1c of 6.9±1.0); 58.1% had CP. There were no differences in anthropometric and biochemical results between patients with or without CP. The ABI was <0.9 in 49% and 25% of patients with and without CP, respectively. Neither were there differences in pulse oximetry in patients with CP or in those with ABI <0.9. The IMT did not change in relation to pulse oximetry, but it was higher in patients with CP and with ABI <0.9 than in patients without alterations. These results were independent of the presence of previous clinical macroangiopathy. Conclusion: Pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM (AU)

[Clinical endocrinologists' perception of the deleterious effects of TSH suppressive therapy in patients with differentiated thyroid carcinoma]. / Percepción de los endocrinólogos clínicos sobre los potenciales efectos perjudiciales del tratamiento supresor de la TSH en el carcinoma diferenciado de tiroides.

OBJECTIVE: To explore the opinion of clinical endocrinologists as to the deleterious effects of thyrotropin (TSH) suppressive therapy in patients with differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: A self-administered survey was sent by e-mail to a group of endocrinologists with expertise in the treatment of patients with differentiated thyroid carcinoma. The questionnaire consisted of three questions related to: 1) the possible adverse effects of this therapy on different organ systems, 2) the clinical significance of these effects and 3) the usefulness of treatment guidelines for DTC. RESULTS: A total of 91 endocrinologists responded with a wide divergence of opinions. No question had more than 80% of answers in a particular option. Of the possible side effects of suppressive therapy, a high degree of ignorance to three of them (increased left ventricular mass, reentrant tachycardia and diastolic dysfunction). Most respondents felt that the seven items, dementia and Alzheimer, decreased quality of life, decreased bone mineral density (BMD) in premenopausal women and men, thromboembolic disease, signs and symptoms of hyperthyroidism and increased risk of fractures were not affected by suppressive therapy, while most responded positively to two items (increased heart rate and decreased BMD in postmenopausal women). Eighty percent of the respondents felt that in any case these effects were not clinically significant and 33% considered that treatment guidelines should be reviewed. CONCLUSIONS: Clinical endocrinologists seem to have a very heterogeneous opinion regarding the potential harmful effects of TSH-suppressive therapy for DTC.

[Usefulness of pulse oximetry in screening of carotid atherosclerosis in patients with type 2 diabetes mellitus]. / Utilidad de la pulsioximetría en el cribado de la aterosclerosis carotídea en pacientes con diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Pulse oximetry of the toes has been suggested in the screening of peripheral arterial disease. We studied the uselfuness of pulse oximetry in detection of type 2 diabetic patients with carotid atherosclerosis. SUBJECTS AND METHODS: 105 patients with type 2 diabetes mellitus (DM) without previous clinical peripheral arterial disease were enrolled. All patients had (1) ankle-brachial index (ABI) measurement, (2) pulse oximetry to measure SaO(2) of their index fingers and big toes in the supine position and at elevated 30cm and (3) a carotid ultrasound [carotid artery intima-media thickness (IMT) and carotid plaques (CP) measurements]. The ABI was considered abnormal when it was <0.9 and when the pulse oximetry showed a decrease in SaO(2) of >2% of the finger compared to foot or to 30cm foot elevation. RESULTS: 60 patients were men (age of 62+/-7 years, HbA(1c) of 6.9+/-1.0); 58.1% had CP. There were no differences in anthropometric and biochemical results between patients with or without CP. The ABI was <0.9 in 49% and 25% of patients with and without CP, respectively. Neither were there differences in pulse oximetry in patients with CP or in those with ABI <0.9. The IMT did not change in relation to pulse oximetry, but it was higher in patients with CP and with ABI <0.9 than in patients without alterations. These results were independent of the presence of previous clinical macroangiopathy. CONCLUSION: Pulse oximetry is not a useful screening method of carotid atherosclerosis in type 2 DM.

Polymorphisms in platelet glycoproteins Ia and IIIa are associated with arterial thrombosis and carotid atherosclerosis in type 2 diabetes.

To determine the genotype distributions of the polymorphisms in platelet glycoproteins (GP) Ib-alpha, Ia/IIa and IIb/IIIa and their association with clinical arterial thrombosis and preclinical carotid atherosclerosis in type 2 diabetes we studied 229 patients with type 2 diabetes and 229 controls matched by age, gender and ethnicity. Biochemical and haemostasis analyses were performed. The GP Ib-alpha VNTR, GP Ia 807 C/T and GP IIIa Pl(A) polymorphisms were determined by PCR. Thrombotic events were registered and carotid atherosclerosis was evaluated by ultrasound examination. A total of 107 patients had clinical atherothrombosis (CA), 65 subclinical atherosclerosis (SA), and 57 had no evidence of atherosclerosis (NA). There were no differences in allele frequencies and the genotype distribution of platelet GP polymorphisms between diabetic patients and controls. The VNTR Ib-alpha polymorphism was not associated with CA. We found a significant association between CA and the 807T (odds ratio [OR]: 2.86, confidence interval [CI]: 1.65-4.93; p<0.001) and PlA2 (OR: 2.03, CI: 1.13-3.65; p=0.03) alleles (in GP Ia and GP IIIa, respectively) in comparison to SA and NA group. Diabetic patients with the coexistence of the 807T and PlA2 alleles presented the highest risk of CA (OR: 3.59, CI: 1.64-7.8; p<0.001). The coexistence of both 807T and PlA2 alleles was also associated with the presence of SA (OR: 9.00, CI: 1.10-73.42; p=0.04). In conclusion, the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination, may confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes.

Regulatory T cells in diabetes and gastritis.

Patients with Type 1 diabetes mellitus (T1D) have an increased prevalence of associated organ-specific autoimmune diseases such as pernicious anemia whose histological substrate is a chronic atrophic gastritis (CAG). Latent pernicious anemia precedes clinically-manifest pernicious anemia and may be difficult to detect solely on simple analytical grounds. We recently described an increased prevalence of clinically-latent pernicious anemia in T1D using low concentrations of pepsinogen I, a zymogen of pepsin present in gastric mucosa, as a useful additional diagnostic marker, besides parietal cell antibodies, for screening latent pernicious anemia in T1D. The failure of peripheral tolerance mechanisms such as regulatory T cells (Treg) might be involved in CAG development in T1D patients. Indeed, functional defects in Tregs have been described in T1D patients. To this end, the percentage of Tregs in peripheral blood of T1D-CAG patients was analyzed and compared with those of a group of T1D without associated autoantibodies and a healthy control group. Tregs levels were also analyzed in gastric biopsies of T1D-CAG patients. The results obtained have led to new questions regarding the pathogenic mechanisms implicated in the development of associated autoimmune diseases in T1D.

Association of the IGF1/pregnancy-associated plasma protein-A system and adipocytokine levels with the presence and the morphology of carotid plaques in type 2 diabetes mellitus patients with stable glycaemic control.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) has been implicated in the atherosclerotic process through regulation of local expression of IGF1. In type 2 diabetes mellitus, glycaemic control has been involved in PAPP-A expression. We compared PAPP-A, IGF1, inflammatory markers and adiponectin concentrations in type 2 diabetic patients with and without carotid plaques and evaluated the relationship between these serum parameters and ultrasound carotid markers of atherosclerosis. METHODS: We studied 125 consecutive type 2 diabetic patients. Clinical data, metabolic variables, hemostatic factors (plasma type-1 plasminogen activator inhibitor, fibrinogen), high-ultrasensitive C reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin, IGF1 and PAPP-A were determined. Patients were classified into two groups according to the presence of carotid plaques on ultrasound. Carotid intima-media thickness (IMT) and morphology of carotid plaques were evaluated. RESULTS: The mean age was 61.5+/-7.3 years and the mean glycated hemoglobin of 6.8+/-0.9%. A total of 60% presented carotid plaques. Both groups were homogeneous in anthropometric data, biochemical determinations and hemostatic factors. Adiponectin, hsCRP, TNF-alpha and IL-6 were similar in both groups. No differences were observed in serum PAPP-A (0.46 (0.22-0.86) vs 0.38 (0.18-0.66) mIU/l and in SDS IGF1 (-0.34+/-1.38 vs -0.67+/-1.35)) in patients with and without carotid plaques respectively. PAPP-A and IGF1 were not correlated with IMT. CONCLUSIONS: Serum PAPP-A and IGF1 do not appear to be useful serum biomarkers for carotid atherosclerosis in type 2 diabetic patients with stable glycemic control, despite scientific evidence of their local role in atherosclerosis.

Regulatory T cells in type 1 diabetic patients with autoimmune chronic atrophic gastritis.

Type A chronic atrophic gastritis (CAG) is increased in type 1 diabetic patients (DM1). To address this issue, we determined and analyzed the number of peripheral blood regulatory T cells (Tregs) in 15 DM1-CAG patients, 15 DM1 patients without associated autoantibodies (DM1) and 15 healthy controls by flow cytometry and compared gastric Tregs expression (CD4+Foxp3+/CD4+) in DM1-CAG patients with that observed in 10 control Helicobacter pylori CAG-infected biopsies. The percentage of peripheral Tregs was higher in DM1-CAG patients compared to DM1 and controls (CD4+Foxp3+: 7.67 +/- 1.91% vs. 5.38 +/- 1.57% and 5.65 +/- 1.76%, P < 0.001, respectively), with no differences between DM1 and controls. Gastric mucosal Tregs were higher in H. pylori CAG than in DM1-CAG patients (31.31 +/- 5.52% vs. 7.68 +/- 3.70%; P < 0.001). Data suggest that Tregs are stimulated in patients with more than one autoimmune disease (DM1 + CAG) in an ineffectual attempt to control autoimmune response and that the number of Tregs in gastric mucosa implicated in the chronification of gastritis differs according to the etiology.