Somatostatin receptors (ssts) are expressed in thyroid cancer cells, but their biological significance is not well understood. The aim of this study was to assess ssts in well differentiated (WDTC) ...and poorly differentiated thyroid cancer (PDTC) by means of imaging and molecular tools and its relationship with the efficacy of somatostatin analog treatment. Thirty-nine cases of thyroid carcinoma were evaluated (20 PDTC and 19 WDTC). Depreotide scintigraphy and mRNA levels of sst-subtypes, including the truncated variant sst5TMD4, were carried out. Depreotide scans were positive in the recurrent tumor in the neck in 6 of 11 (54%) PDTC, and in those with lung metastases in 5/11 cases (45.4%); sst5TMD4 was present in 18/20 (90%) of PDTC, being the most densely expressed sst-subtype, with a 20-fold increase in relation to sst2. In WDTC, sst2 was the most represented, while sst5TMD4 was not found; sst2 was significantly increased in PDTC in comparison to WDTC. Five depreotide positive PDTC received octreotide for 3-6 months in a pilot study with no changes in the size of the lesions in 3 of them, and a significant increase in the pulmonary and cervical lesions in the other 2. All PDTC patients treated with octreotide showed high expression of sst5TMD4. ROC curve analysis demonstrated that only sst5TMD4 discriminates between PDTC and WDTC. We conclude that sst5TMD4 is overexpressed in PDTC and may be involved in the lack of response to somatostatin analogue treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Monogenic diabetes caused by changes in the gene that encodes insulin (INS) is a very rare form of monogenic diabetes (<1%). The aim of this work is to describe the clinical and glycaemic control ...characteristics over time from four members of a family diagnosed with monogenic diabetes with the novel mutation: c.206del,p.(Gly69Aalfs*62) located in exon 3 of the gene INS. 75% are females, with debut in adolescence and negative autoimmunity. In all cases, C-peptide is detectable decades after diagnosis (>0.6ng/ml). Currently, patients are being treated either with insulin in a bolus-basal regimen, oral antidiabetics or hybrid closed loop system. Monogenic diabetes due to mutation in the INS is an entity with heterogeneous presentation, whose diagnosis requires high suspicion and presents an important clinical impact. Given the lack of standards in this regard, therapy must be individualized, although insulin therapy could help preserve beta cell functionality in these subjects.
La diabetes causada por cambios en el gen que codifica la insulina (INS) es una forma rara de diabetes monogénica (<1%). El objetivo del presente trabajo fue describir las características clínicas y de control glucémico a lo largo de la evolución de 4 miembros de una familia diagnosticados de diabetes monogénica con la mutación no descrita: c.206del,p.(Gly69Aalfs*62) localizada en el exón 3 del gen INS. El 75% fueron mujeres, con inicio en la adolescencia y autoinmunidad negativa. En todos los casos, el péptido C fue detectable décadas después del diagnóstico (>0,6ng/ml). Actualmente, los pacientes reciben tratamiento con insulina en un régimen de bolo basal, antidiabéticos orales o un sistema híbrido de circuito cerrado. La diabetes monogénica por mutación en el INS es una entidad de presentación heterogénea, cuyo diagnóstico requiere alta sospecha y presenta un impacto clínico importante. Ante la falta de estándares al respecto, la terapia debe ser individualizada, aunque el tratamiento con insulina podría ayudar a preservar la funcionalidad de las células beta en estos sujetos.
To assess safety and benefits of continuous subcutaneous insulin infusion (CSII) therapy in a cohort of type 1 diabetes patients in Spain.
A web-based national registry was created by the Working ...Group of the Spanish Diabetes Association. All patients on CSII being followed at selected referral centers were included. A cross-sectional analysis was performed.
A total of 1275 patients were included. Data completion for patients on CSII was 67 ± 32%. Indications for treatment were suboptimal glycemic control (32%), high glucose variability (24%), preconception care (14%) and hypoglycemia (11%). In the patients on CSII for ≥1 year (n = 843, mean CSII duration of 5 years), HbA1c decreased by 5 mmol/mol (0.5%) in the whole population and by 8 mmol/mol (0.7%) in subjects with suboptimal glycemic control as CSII indication. Percentage of patients achieving HbA1c ≤ 53 mmol/mol (7%) increased from 20% before CSII to 34% at the end of follow-up. Severe hypoglycemia decreased from 29% to 5%. The rate of discontinuation was 9.5%. HbA1c was lower in patients using bolus advisor and temporary basal rates.
CSII was associated with a sustained improvement in glycemic control and a reduction in severe hypoglycemia. The use of advanced CSII settings was related to better glycemic control.
To evaluate the adequacy of TSH suppression therapy (TSHst) at the first disease assessment and the last follow-up visit.
Retrospective observational study of those patients under follow-up of DTC in ...a reference hospital.
216 patients (79.2% women) were evaluated, with a mean age 59.0 ± 13.1 years-old and a mean follow-up of 6.9 ± 4.3 years. 88.4% were papillary carcinomas.
At diagnosis, 69.2% had a low risk of recurrence (RR) compared to 13.6% with a high RR. Dynamic risk stratification (DRS) classified patients at first disease assessment and the last visit as excellent response (ER) in 60.0% and 70.7%, respectively.
Those patients with ER in the first and last follow-up control maintained TSHst in 30.7% and 16.3% of the cases, respectively (p < 0.001).
The factors associated with maintaining TSHst at the last control were younger age, higher RR at diagnosis, DRE at follow-up, presence of multifocality and histological vascular invasion (p < 0.05).
In a logistic regression analysis adopting tsTSH at follow-up as the dependent variable, exclusively age (β = −0.062; p < 0.001), RR at diagnosis (β = 1.074; p < 0.05) and EDR during follow-up (β = 1.237; p < 0.05) maintained statistical significance.
Despite the current recommendations, 30.7% of patients with low RR and initial ER are under TSHst. This percentage reduced to 16.3% in those patients with ER after a mean follow-up of 6.9 years. Age, baseline RR, and DRE during follow-up were associated to maintaining tsTSH.
Evaluar la adecuación de la supresión de TSH (tsTSH) al diagnóstico y en la última visita de seguimiento.
Estudio observacional retrospectivo en aquellos pacientes en seguimiento por CDT en un hospital de tercer nivel.
Se evaluaron 216 pacientes (79,2% mujeres), edad media 59,0 ± 13,1 años y un seguimiento medio de 6,9 ± 4,3 años. Un 88,4% fueron carcinomas papilares.
Al diagnóstico el 69,2% presentaban un riesgo bajo de recurrencia (RR) frente a un 13,6% de RR elevado. La estadificación dinámica del riesgo (EDR) clasificó a los pacientes, inicialmente y en la última visita, como respuesta excelente (RE) en un 60,0% y un 70,7%, respectivamente.
Aquellos pacientes con RE en el primer y último control de seguimiento, mantuvieron tsTSH en un 30,7% y 16,3% de los casos, respectivamente(p < 0,001).
Los factores asociados a mantener la tsTSH en la última visita de control fueron la menor edad, mayor RR al diagnóstico, la EDR en el seguimiento, la presencia de multifocalidad e invasión vascular (p < 0,05).
En un modelo de regresión logística adoptando la tsTSH en el seguimiento como variable dependiente, exclusivamente la edad (β = −0,062; p < 0,001), el RR al diagnóstico (β = 1,074; p < 0,05) y la EDR en el seguimiento (β = 1,237; p < 0,05) mantuvieron la significación estadística.
A pesar de las recomendaciones actuales, un 30,7% de los pacientes con bajo RR y RE inicial se encuentran bajo tsTSH. Este porcentaje se redujo al 16,3% en RE tras un seguimiento medio de 6,9 años. La edad, el RR inicial y la EDR durante el seguimiento se relacionaron con mantener la tsTSH.
Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in ...real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry.
We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy.
We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment.
This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.
Resumen Antecedentes y objetivo: la hipercolesterolemia familiar heterocigota (HFH) es el trastorno del metabolismo lipídico monogénico más común que se asocia a patología cardiovascular prematura. ...Nuestro objetivo fue describir el grado de control metabólico, el perfil cardiovascular y la adherencia a la dieta mediterránea de una cohorte de pacientes con HFH. Material y métodos: estudio de cohortes retrospectivo de casos índices y familiares diagnosticados genéticamente de HFH desde 2009 a 2017. Se analizaron los datos antropométricos, clínicos, analíticos, del estudio genético y del tratamiento. Resultados: se estudiaron 138 sujetos con una edad media de 48,8 (,) años, el 55,8 % mujeres. Se encontró la mutación positiva en el 55,8 %. La media de colesterol total al diagnóstico fue de 281,1 (68,) mg/dl y la de LDL de 204 (65) mg/dl. El 10,1 % presentaban cardiopatía isquémica previa. Entre los casos familiares se observó una menor edad media 32,89 (,) años vs. 50,3 (,) años, p < 0,001, así como valores de LDL inferiores en el momento del diagnóstico 181,9 (64,) mg/dl vs. 226,8 (52) mg/dl, p < 0,005 en comparación con los casos índice. Se evidenció una correlación positiva entre dosis de tratamiento hipolipemiante y reducción de los niveles de LDL (r = 0,254, p < 0,05), aunque solo el 30 % de los pacientes alcanzaron sus objetivos de LDL. Los pacientes con HFH presentaron una elevada adherencia a la dieta mediterránea, con una puntuación media de 9,5 (,) en el test Predimed. Conclusiones: la detección precoz de la HFH es necesaria para prevenir eventos cardiovasculares prematuros. El diagnóstico de casos familiares anticipa el tratamiento de los pacientes con HFH. Los pacientes con HFH están más sensibilizados sobre la adherencia a las dietas cardiosaludables.
A polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism (rs1049353) with potential implications in weight loss. We decide to investigate the role of ...this polymorphism on metabolic changes and weight loss secondary to treatment with liraglutide.
A population of 86 patients with diabetes mellitus type 2 and obesity, unable to achieve glycemic control (hemoglobine glycate A1c >7%) with metformin alone or associated to sulfonylurea, who require initiation of liraglutide treatment in progressive dose to 1.8 mg/d subcutaneously, was analyzed.
Fifty-one patients (59.3%) had the genotype G1359G, and 35 patients (40.7%) had G1359A (28 patients, 32.6%) or A1359A (7 patients, 8.1%) (A allele carriers). In patients with both genotypes, basal glucose, HbA1c, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased. In patients with G1359G genotype, total cholesterol and low-density lipoprotein cholesterol decreased, and in patients with A allele, homeostasis model assessment for insulin resistance decreased, too.
There is an association of the A allele with an improvement of insulin resistance secondary to weight loss after liraglutide treatment in obese patients with diabetes mellitus type 2. Noncarriers of A allele showed an improvement in cholesterol levels after weight loss.
To evaluate metabolic control and satisfaction with a telemedicine diabetes education programme for the initiation of flash glucose monitoring (FGM) in type 1 diabetes.
Prospective study in 48 ...patients (52.1% women, 22.9% on insulin pump) who started FGM. They were analysed at baseline and 3 months after the beginning of the FGM. The results were compared with an on-site learning cohort matched by age, sex and HbA1c.
At the beginning and 3 months after the MFG, HbA1c improvement was observed (7.9±1.4 vs 7.3±1.1%), p<0.01; with a decrease in time below range - TBR - (4.7±4.9 vs 3.5±3.5%), p<0.05 and number of hypoglycaemic events (9.4±8.7 vs 6.9±5.7/15 days), p<0.05, associated with a worsening in time above range - TAR - (33.5±19.9 vs 37.0±20.9%), p<0.05. No significant differences were observed in the TIR 70–180mg/dl (61.7±18.6 vs 59.4±20.0%), glycemic variability or the use of FGM. Patient satisfaction with telemedicine training was 4.8±0.3 out of 5.
No significant differences were observed in the follow-up, either in HbA1c or other glucometer parameters between on-site and online training.
In a multivariate analysis adopting the HbA1c at follow-up as the dependent variable, only the TIR (β=−0.034; p<0.001) and the initial HbA1c (β=0.303; p<0.001) maintained statistical significance, unrelated to the on-site or online training (β=0.136; p=ns).
A telemedicine programme is an adequate tool for training in FGM, with results similar to on-site training, and it was associated with a high degree of satisfaction.
Evaluar el control metabólico y la satisfacción con un programa de educación terapéutica en diabetes mediante telemedicina para el inicio de la monitorización flash de glucosa (MFG) en diabetes tipo 1.
Estudio prospectivo en 48 pacientes (52,1% mujeres, 22,9% en tratamiento con bomba de insulina) que iniciaron MFG. Se analizaron basalmente y a los 3 meses tras el inicio del MFG. Los resultados se compararon con una cohorte de formación presencial pareada por edad, sexo y HbA1c.
Al comparar los resultados al inicio y a los 3 meses de la MFG se observó una mejoría en HbA1c (7,9±1,4 vs 7,3%±1,1), p<0,01; tiempo por debajo del rango–TBR-(4,7±4,9 vs 3,5±3,5%), p<0,05 y número de eventos de hipoglucemia(9,4±8,7 vs 6,9±5,7/15días), p<0,05, asociado a un empeoramiento del tiempo por encima del rango–TAR-(33,53±19,9 vs 37,0±20,9%) p<0,05. No se observaron diferencias significativas en el TIR 70–180mg/dl (61,7±18,6 vs 59,4±20,0%), parámetros de variabilidad glucémica o del uso del dispositivo. La satisfacción de los pacientes con la formación por telemedicina fue de 4,8±0,3 sobre 5.
No se observaron diferencias significativas en el seguimiento, ni en HbA1c ni otras glucométricas, entre la formación presencial frente a la telemática.
Al realizar un análisis multivariante adoptando la HbA1c de seguimiento como variable dependiente, exclusivamente el TIR (β=−0,034; p<0,001) y la HbA1c inicial (β=0,303; p<0,001) mantuvieron la significación estadística, sin relación con la formación online o presencial (β=0,136; p=ns).
La consulta de telemedicina es una herramienta adecuada para la formación en MFG con resultados similares a la consulta presencial y presenta un alto grado de satisfacción.
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