Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly.

Acromegaly is a hormonal disorder resulting from excessive growth hormone (GH) secretion frequently produced by pituitary adenomas and consequent increase in insulin-like growth factor 1 (IGF-I). Elevated GH and IGF-I levels result in a wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Somatostatin analogues (SSAs) form the basis of medical therapy for acromegaly and are currently used as first-line treatment or as second-line therapy in patients undergoing unsuccessful surgery. However, a considerable percentage of patients do not respond to SSAs treatment. Somatostatin receptors (SSTR1-5) and dopamine receptors (DRD1-5) subtypes play critical roles in the regulation of hormone secretion. These receptors are considered important pharmacological targets to inhibit hormone oversecretion. It has been proposed that decreased expression of SSTRs may be associated with poor response to SSAs. Here, we systematically examine SSTRs and DRDs expression in human somatotroph adenomas by quantitative PCR. We observed an association between the response to SSAs treatment and DRD4, DRD5, SSTR1 and SSTR2 expression. We also examined SSTR expression by immunohistochemistry and found that the immunohistochemical detection of SSTR2 in particular might be a good predictor of response to SSAs.

Advanced thyroid carcinoma in pregnancy: case report of two pregnancies.

Differentiated thyroid carcinoma is one of the most frequently diagnosed cancers during pregnancy, second only to breast cancer. Therefore, it would be of value to determine if there are pregnancy-related physiological effects that impact long-term prognosis for patients with this disease. Hormone effects attributable to ß-human chorionic gonadotropin and estrogens seem particularly likely. We present a case of a 40-year-old woman with thyroid follicular carcinoma with accompanying bone metastases. The cancer was discovered immediately after childbirth and the woman became pregnant again when the disease was in an advanced stage. We describe the cancer evolution and present the maternal and fetal results. Pregnancy in women with advanced thyroid carcinoma could affect long-term prognosis. However, more studies are needed to evaluate this hypothesis. In this unique case, there were two pregnancies and the second occurred in an advanced state of the disease. We evaluated how these pregnancies could affect short-term prognosis of the disease.

The lack of consensus in management of malignant struma ovarii.

Struma ovarii is a rare variant of teratoma characterized by the presence of thyroid tissue in more than 50%. Malignant transformation is rare (less than 5%) and the criteria to classify this condition have changed over time. Nowadays it must fulfill the histological categories of differentiated thyroid carcinoma. Its treatment is controversial and there is no unanimous management. We present three cases of women with malignant struma ovarii, diagnosed by the surgical specimen.

Effectiveness and Safety of an Advanced Hybrid Closed-Loop System in Adolescents and Adults with Type 1 Diabetes Previously Treated with Continuous Subcutaneous Insulin Infusion and Flash Glucose Monitoring.

This study aimed to evaluate the effectiveness and safety of the MiniMed™ 780G advanced hybrid closed-loop (AHCL) system in people with type 1 diabetes (T1D) previously treated with continuous subcutaneous insulin infusion combined with flash glucose monitoring in a real-life setting. A total of 47 subjects (mean age 41 ± 13.6 years, 60% females, diabetes duration 28 ± 11 years) were included and switched to an AHCL system. Baseline and 6-month data were analyzed. Time in range 70-180 mg/dL increased from 65.3% at baseline to 73.8% at 6 months. Time in hyperglycemia >180 mg/dL decreased from 26.6% to 19.3%. Time in hypoglycemia <70 mg/dL decreased from 4.6% to 2.3%. The coefficient of variation also decreased from 36% to 31.6%. No episodes of severe hypoglycemia, diabetes ketoacidosis, or diabetes-related hospital admissions occurred. In conclusion, the MiniMed 780G AHCL system enables the safe achievement of recommended glycemic targets in people with T1D after 6 months of use.

Telemedicine screening program for diabetic retinopathy in patients with type 1 diabetes mellitus.

PURPOSE: To analyze the results of the telemedicine screening program for diabetic retinopathy (DR) in patients with type 1 diabetes conducted by the Endocrinology and Nutrition Management Unit of Virgen del Rocío University Hospital. METHODS: This cross-sectional study comprised patients with type 1 diabetes mellitus (DM) in our DR screening program from January 2018 to November 2020. Fundus photographs are performed by trained nurses and reviewed by a trained endocrinologist. Those suggestive of pathology are sent to ophthalmology through a telematic program for review. RESULTS: Of the 995 fundus photographs evaluated, 646 (65.3%) showed no evidence of DR, 327 (33.1%) presented possible DR, and 16 (1.6%) were not gradable. The diagnosis was confirmed in 254 patients after reviewing by ophthalmology, and the screening program achieved a positive predictive value for DR of 77.7%. Seventy-three were excluded by ophthalmology due to the absence of DR (false positive rate - 22.3%). In 92.5% of the cases classified by the ophthalmologist, the degree of DR was mild or very mild. CONCLUSION: Our telemedicine screening program for DR in patients with type 1 DM is consistent with the literature. Effective screening for DR is performed, with patients diagnosed in the early stages. Telemedicine programs facilitate efficient communication among healthcare personnel.

Outcomes of a multidisciplinary Diabetic Foot Day Unit.

OBJECTIVE: To analyse the main characteristics of patients and the health outcomes obtained and to evaluate the impact of peripheral artery disease (PAD) in patients treated in our multidisciplinary Diabetic Foot Unit. RESEARCH DESIGN AND METHODS: Observational prospective study. 273 patients from two different populations (with and without PAD - classified according to the presence of distal pulses) treated over a 14-month period in the multidisciplinary Diabetic Foot Unit were included. The data on patient characteristics and outcomes were analysed for the purpose of comparison. For the inference study, a comparison of medians with the non-parametric test for independent samples for the quantitative variables and a χ2 test for the comparison of proportions in qualitative variables were performed. RESULTS: Patients with PAD ulcers were older (60 (54-67) vs. 64 (75-81), p=0.000) and had a higher macrovascular burden (8.1% vs. 29% for ischaemic heart disease history, p=0.000; 6.7% vs. 18.1% for cerebrovascular disease history, p=0.004). Their Texas Score was higher (p=0.000) and their major amputation rate was higher (1.4% vs. 12.3%, p=0.001). They had less background of previous ulcers (52.6% vs. 26.8%, p=0.000), their episode duration was shorter (4 (0-10) vs. 0 (0-3) weeks, p=0.000), and their proportional need for antibiotic therapy was lower (64.4% vs. 51.4%, p=0.03). CONCLUSIONS: The differences found between ulcers with and without vascular involvement support the need for a different approach and for the inclusion of vascular surgeons on the team. The multidisciplinary care model for diabetic foot patients could be effective and improve health outcomes.

Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice.

Objectives: The aim of this study is to investigate in depth diabetes mellitus associated with immune checkpoint inhibitors (DM-ICIs) by analysing a case series. We also evaluated the clinical impact of flash glucose monitoring (FGM) systems in the management of this entity. Methods: We conducted an observational cohort study of DM-ICIs diagnosed in two hospitals in Seville (Spain). Patients with a new diagnosis of diabetes mellitus (DM) or with sudden worsening of preexisting DM after starting treatment with ICIs, with a random 5 hour-postprandial C-peptide value of <0.6 nmol/L and without possibility of subsequent withdrawal of insulin treatment, were included. Results: A total of 7 cases were identified, mostly males (n = 6; 85.7%), with a mean age of 64.9 years. The mean glycated hemoglobin (HbA1c) upon diagnosis was 8.1%, with diabetic ketoacidosis (DKA) observed in 6 cases (85.7%). Subcutaneous flash glucose monitoring (FGM) systems were used in six cases, with a mean follow-up period of 42.7 weeks. During the first 90 days of use, mean average glucose was 167.5 mg/dL, with a coefficient of variation (CV) of 34.6%. The mean time in the range 70-180 mg/dL (TIR) was 59.7%, with a mean time above range (TAR) 181-250 mg/dL of 27.8% and a mean TAR > 250 mg/dL of 10.2%. The mean time below range (TBR) 54-69 mg/dL was 2%, while the mean TBR < 54 mg/dL was 0.3%. The mean glucose management indicator (GMI) was 7.3%. No significant differences were observed in FGM values for the following 90 days of follow-up. A progressive improvement in all parameters of glycaemic control was observed between the first month of FGM use and the sixth month of FGM use. Of note, there was a decrease in mean CV (40.6% to 34.1%, p = 0.25), mean TAR 181-250 (30.3% to 26%, p = 0.49), mean TAR > 250 mg/dL (16.3% to 7.7%, p = 0.09), mean TBR 54-69 mg/dL (5.2% to 2%, p = 0.16), and mean TBR < 54 mg/dL (1.8% to 0.2%, p = 0.31), along with an increase in mean values of TIR 70-180 mg/dL (46.5% to 60.5%, p = 0.09). The lack of statistical significance in the differences observed in the mean FGM values over the follow-up period may be related to the small sample size. Conclusion: DM-ICI is recognised by a state of sudden-onset insulinopenia, often associated with DKA. The use of FGM systems may be a valid option for the effective management of DM-ICIs and for the prevention of severe hyperglycaemic and hypoglycaemic episodes in this condition.

Description of a Cohort of Type 1 Diabetes Patients: Analysis of Comorbidities, Prevalence of Complications and Risk of Hypoglycemia.

BACKGROUND: Despite major medical advances, Type 1 Diabetes (T1D) patients still have greater morbimortality than the general population. Our aim was to describe our cohort of T1D patients and identify potential risk factors susceptible to prevention strategies. METHODS: Cross-sectional, observational study, including T1D patients treated at our center, from 1 March 2017 to 31 March 2020. INCLUSION CRITERIA: T1D, age > 14 years and signed informed consent. EXCLUSION CRITERIA: diabetes other than T1D, age < 14 years and/or refusal to participate. RESULTS: Study population n = 2181 (49.8% females, median age at enrollment 41 years, median HbA1c 7.7%; 38.24% had at least one comorbidity). Roughly 7.45% had severe hypoglycemia (SH) within the prior year. Macro/microvascular complications were present in 42.09% (5.83% and 41.14%, respectively). The most frequent microvascular complication was diabetic retinopathy (38.02%), and coronary disease (3.21%) was the most frequent macrovascular complication. The risk of complications was higher in males than in females, mainly macrovascular. Patients with SH had a higher risk of complications (OR 1.42; 1.43 in males versus 1.42 in females). CONCLUSIONS: Our T1D population is similar to other T1D populations. We should minimize the risk of SH, and male patients should perhaps be treated more aggressively regarding cardiovascular risk factors.

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features.

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST1-5 expression was also evaluated by immunohistochemistry. SST3 was the predominant SST subtype detected, followed by SST2, SST5, and SST1. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST2 and SST5. No major association between SSTs and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs.

New laparoscopic assisted percutaneous gastrostomy. Description and comparison with others gastrostomy types.

INTRODUCTION: Gastrostomy feeding tube insertion has become a common procedure as it enables patients who require long term enteral feeding. Conventional surgical gastrostomies were the only way of gaining enteral access in patients in which it is not possible to pass an endoscope or a nasogastric tube required for endoscopic or radiological gastrostomies, and in patients in which certain anatomical abnormalities contraindicate performing these techniques. As conventional surgical gastrostomies are associated with high morbidity, especially gastric leakage around the tube, percutaneous laparoscopic assisted gastrostomy (PLAG) may be a better way to gain enteral access. MATERIAL AND METHODS: Observational study of a prospective cohort of 224 patients on whom a gastrostomy was performed for nutritional support between January 2009 and October 2015 at Virgen del Rocío University Hospital in Seville. The types of gastrostomies carried out were: percutaneous endoscopic gastrostomy (PEG, n = 106), percutaneous radiological gastrostomy (PRG, n = 89), conventional surgical gastrostomy, Open Stamn or Laparoscopic Janeway (SG, n = 9) and percutaneous laparoscopic assisted gastrostomy (PLAG, n = 20), technique that we describe in detail. Short and long term complications are described. RESULTS: Many more complications were seen in the conventional gastrostomy group than in the other three groups, especially leakage of gastric content around the tube, with burning and irritation of the skin (66% compared with 2.83% in PEG and 0% in PLAG and PRG). The group with the highest proportion of patients completely free of complications was PLAG (75%), whilst in the conventional surgical gastrostomy group, no patient was completely free of complications. CONCLUSIONS: We found lower complication rate in PLAG than any other technique. We believe that PLAG could be preferred technique for patients on whom it is not possible to perform PEG or PRG, as it is safe and easy.

[Bariatrica paraplegia patient and morbid obesity. New challenge in bariatric surgery]. / Paciente con paraplejia y obesidad mórbida; nuevo reto en la cirugía bariátrica.

The loss of mobility due to spinal cord injury is a risk factor for weight gain. Despite the well-documented outcomes of bariatric surgery in outpatients, little information is available about the surgery in paraplegic patients. We present two cases of patients with morbid obesity and spinal cord injury. After several attempts to lose weight conservatively, were assessed by the multidisciplinary team of our hospital and finally intervened by laparoscopic gastric bypass. After surgery have been no post-surgical complications. The patient in case 1, after two years of follow-up, a weight of 84 kg (BMI 25.08 kg/m2). Case 2, after a month of surgery has reduced weight and stopped taking antihypertensive therapy. It 's available to bariatric surgery as an important option to consider if all non-surgical interventions fail is highlighted.

La pérdida de la movilidad, como consecuencia de una lesión medular, es un factor de riesgo para el aumento de peso. A pesar de los resultados bien documentados de la cirugía bariátrica en pacientes ambulatorios, hay poca información disponible acerca de la cirugía en pacientes parapléjicos. Presentamos dos casos clínicos de pacientes con obesidad mórbida y lesión medular. Tras varios intentos para perder peso de forma conservadora, fueron valorados por el equipo multidisciplinar de nuestro hospital y finalmente se intervinieron mediante bypass gástrico por vía laparoscópica. El caso 1, tras dos años de seguimiento, presenta un peso de 84 kg (IMC 25,08 kg/m2). El caso 2, tras un mes de la cirugía ha reducido de peso y ha dejado de tomar tratamiento hipotensor. En ellos, destaca la disposición de la cirugía bariátrica como una opción a tener en cuenta si todas las intervenciones no quirúrgicas fracasan.

[Gastrocolic fistula as a complication of percutaneous feeding gastrostomy, description of three cases and review of the literature]. / Fístula gastrocólica como complicación de gastrostomía percutánea de alimentación, a propósito de tres casos y revisión de la literatura.

INTRODUCTION: Percutaneous gastrostomy, is the procedure of choice to provide enteral access in patients requiring nutritional support in this way in the long run, relegating the surgical gastrostomy. MATERIAL AND METHODS: We present three patients requiring percutaneous gastrostomy for nutritional support. In two cases was performed endoscopic gastrostomy and another one using interventional radiology. RESULTS: While performing percutaneous gastrostomy clinical incidents were not detected, but when trying the replacement of gastrostomy tubes, showed the presence of gastrocolic fistula that caused failure or turnover in one case, or abdominal pain and diarrhea in the two other cases. DISCUSSION: Despite being a safe technique, should be done a proper patient selection in order to minimize the potential complications that may occur, as gastrocolic fistula, recommending in doubtful cases test of image such CT (computerized Tomography).

Introducción: La gastrostomía percutánea es el procedimiento de elección para proporcionar acceso enteral en pacientes que requieren soporte nutricional por esta vía a largo plazo, relegando a la gastrostomía quirúrgica. Material y métodos: Presentamos tres pacientes con indicación de gastrostomía percutánea para soporte nutricional. En dos casos se realizó la gastrostomía mediante endoscopia y en otro mediante radiología intervencionista. Resultados: Durante la realización de las gastrostomías no se detectaron incidencias clínicas, pero al intentar recambio de las sondas de gastrostomía, se evidenció la presencia de fístula gastrocólica que, ocasionaba imposibilidad del recambio en un caso, o cuadro de dolor abdominal y diarrea en los otros dos casos. Discusión: Pese a ser una técnica segura, la gastrostomía percutánea debe realizarse con una correcta selección de los pacientes para minimizar posibles complicaciones que puedan acontecer, como fístula gastrocólica, recomendando en casos dudosos la realización de prueba de imagen tipo TC (tomografía computerizada).