Multiple overlapping microwave ablation in benign thyroid nodule: a single-center 24-month study.

Objective: This study aimed to evaluate the safety and long-term efficacy using the multiple overlapping ablation technique with a novel non-cooled microwave system in benign symptomatic thyroid nodules. Methods: This prospective cohort single-center study collected complication data from the start of the procedure to 30 days postoperatively and evaluated the safety and effectiveness with a follow-up of 24 months. Ultrasound examinations were performed to determine the volume shrinkage during follow-up. Thyroid function cosmetic and symptoms scores and satisfaction degree were evaluated. Results: A total of 30 symptomatic benign thyroid nodules were treated by microwave ablation using a power between 15 and 30 W depending on the size of the nodule to be treated. The volume reduction rates in months 1, 3, 6, 9, 12, and 24 after ablation were 32, 59, 67, 69, 73, and 81%, respectively. The mean symptom score and mean cosmetic score before treatment were 4 and 3, respectively, while after treatment they dropped to 3 and 1, respectively. Thyroid function indicators fluctuated in the normal range and those with hyperthyroidism recovered to normal parameters. One case of temporary laryngeal paralysis occurred postoperatively and fully recovered in less than 3 months. Conclusions: The novel microwave ablation system presented herein can help achieve good clinical success rate in benign thyroid nodules with a satisfying safety profile. The microwave ablation performed with the multiple overlapping ablation technique could be a good alternative to surgery and radiofrequency ablation in the management of benign thyroid nodules.

[Executive Summary from Expert consensus on effectiveness and safety of iDPP-4 in the treatment of patients with diabetes and COVID-19]. / Resumen Ejecutivo del Consenso de expertos sobre la eficacia y seguridad de los iDPP-4 en el tratamiento de pacientes con diabetes y COVID-19.

BACKGROUND: This consensus aims to clarify the role of Dipeptidyl Peptidase-4 inhibitors (iDPP-4) in managing patients with diabetes during the COVID-19 pandemic. MATERIALS AND METHODS: A PubMed bibliographic search was carried out (December 2019-February 2021). Oxford methodology was used for the evaluation of evidence and possible recommendations were established by consensus. RESULTS: Diabetes appears to be an independent factor in COVID-19 disease (evidence 2b). No increased risk of contagion with iDPP-4 is demonstrated (evidence 2b), and its use has been shown to be safe (evidence 2b). The use of this drug may present a specific benefit in reducing mortality, particularly in in-hospital use (evidence 2a), reducing admission to intensive care units (evidence 2b) and the need for mechanical ventilation (evidence 2b). CONCLUSIONS: The use of iDPP-4 appears to be safe in patients with COVID-19, and quality studies are needed to clarify their possible advantages further.

Executive Summary from Expert consensus on effectiveness and safety of iDPP-4 in the treatment of patients with diabetes and COVID-19.

BACKGROUND: This consensus aims to clarify the role of Dipeptidyl Peptidase-4 inhibitors (iDPP-4) in managing patients with diabetes during the COVID-19 pandemic. MATERIALS AND METHODS: A PubMed bibliographic search was carried out (December 2019-February 2021). Oxford methodology was used for the evaluation of evidence and possible recommendations were established by consensus. RESULTS: Diabetes appears to be an independent factor in COVID-19 disease (evidence 2b). No increased risk of contagion with iDPP-4 is demonstrated (evidence 2b), and its use has been shown to be safe (evidence 2b). The use of this drug may present a specific benefit in reducing mortality, particularly in in-hospital use (evidence 2a), reducing admission to intensive care units (evidence 2b) and the need for mechanical ventilation (evidence 2b). CONCLUSIONS: The use of iDPP-4 appears to be safe in patients with COVID-19, and quality studies are needed to clarify their possible advantages further.

Differential effects of HNF-1α mutations associated with familial young-onset diabetes on target gene regulation.

Hepatocyte nuclear factor 1-α (HNF-1α) is a homeodomain transcription factor expressed in a variety of tissues (including liver and pancreas) that regulates a wide range of genes. Heterozygous mutations in the gene encoding HNF-1α (HNF1A) cause familial young-onset diabetes, also known as maturity-onset diabetes of the young, type 3 (MODY3). The variability of the MODY3 clinical phenotype can be due to environmental and genetic factors as well as to the type and position of mutations. Thus, functional characterization of HNF1A mutations might provide insight into the molecular defects explaining the variability of the MODY3 phenotype. We have functionally characterized six HNF1A mutations identified in diabetic patients: two novel ones, p.Glu235Gly and c-57-64delCACGCGGT;c-55G>C; and four previously described, p.Val133Met, p.Thr196Ala, p.Arg271Trp and p.Pro379Arg. The effects of mutations on transcriptional activity have been measured by reporter assays on a subset of HNF-1α target promoters in Cos7 and Min6 cells. Target DNA binding affinities have been quantified by electrophoretic mobility shift assay using bacterially expressed glutathione-S-transferase (GST)-HNF-1α fusion proteins and nuclear extracts of transfected Cos7 cells. Our functional studies revealed that mutation c-57-64delCACGCGGT;c-55G>C reduces HNF1A promoter activity in Min6 cells and that missense mutations have variable effects. Mutation p.Arg271Trp impairs HNF-1α activity in all conditions tested, whereas mutations p.Val133Met, p.Glu235Gly and p.Pro379Arg exert differential effects depending on the target promoter. In contrast, substitution p.Thr196Ala does not appear to alter HNF-1α function. Our results suggest that HNF1A mutations may have differential effects on the regulation of specific target genes, which could contribute to the variability of the MODY3 clinical phenotype.

[Risk factors of persistent disease at 5 years from diagnosis in differentiated thyroid cancer: study of 63 patients]. / Factores relacionados con la persistencia de la enfermedad a los 5 años del diagnóstico de cáncer diferenciado de tiroides: estudio de 63 pacientes.

OBJECTIVE: To identify possible risk factors associated with persistent disease 5 years after total or near-total thyroidectomy in patients with differentiated thyroid cancer (DTC). PATIENTS AND METHOD: Retrospective study evaluating data from 63 patients 5 years after they were first diagnosed of DTC. At this time of the study, 46 subjects were considered disease-free (F group) whereas 17 had evidence of persistent disease or had died from DTC (P group). We compared both groups of patients regarding the following variables: a) variables at diagnosis related to the patient (age, gender) and the tumor (histological type, size, extrathyroidal involvement, vascular invasion, multifocality, lymph node and distant metastases), and b) variables recorded during follow-up: percentage of subjects showing serum stimulated thyroglobulin > or = 10 ng/ml few weeks postoperatively (Tg0) and 6 to 12 months later (Tg1). RESULTS: Male gender, extrathyroidal involvement and lymph node metastases were more frequent in P group than in F group (41 vs. 11%, 60 vs. 18% and 50 vs. 5.5%; p < 0.05). During the follow-up the percentage of patients showing Tg > or = 10 ng/ml was higher in P group compared to F group, both at a few weeks postoperatively and 6 to 12 months later (Tg0, 75 vs. 13%; Tg1, 69% vs. 0; p < 0,05). CONCLUSIONS: In our patients, male gender, extrathyroidal involvement, and lymph node metastases at diagnosis were associated with persistent disease 5 years later. Serum stimulated thyroglobulin had a very high predictive value both just after surgery and in the next 6 to 12 months and could help identifying subjects who need a closer follow-up.

Hypophysitis following Treatment with Ustekinumab: Radiological and Pathological Findings.

CONTEXT: Ustekinumab is a human IgG1 monoclonal antibody that targets interleukin (IL)-12 and IL-23, which may be useful in the treatment of autoimmune conditions such as psoriasis, psoriatic arthritis, and Crohn's disease. Hypophysitis is an immune-derived inflammatory condition of the pituitary gland that may lead to pituitary dysfunction. With the increasing use of immunotherapy, it is possible that this and other new immune-related adverse events (IRAEs) arise, although the mechanisms involved are still incompletely defined. CASE DESCRIPTION: A 35-year-old male, with a previous history of severe plaque-psoriasis who had started treatment with ustekinumab 4 months before, complained of progressive and persistent headache. Brain magnetic resonance imaging (MRI) was unremarkable. One year later, a new MRI was performed due to headache persistence, which revealed a homogenous and diffuse pituitary enlargement, with suprasellar extension and optic chiasm involvement, blurring of the pituitary stalk, absence of clear differentiation between the anterior and posterior lobes, and no signs of hemorrhage or adenomas. Endocrine evaluation was consistent with panhypopituitarism. Work-up of infiltrative and infectious diseases was negative. Follow-up MRI revealed an increase in the pituitary enlargement and transsphenoidal surgery was performed. Pathological findings revealed an intense fibrosis and a chronic inflammatory infiltrate, but no evidence of adenoma, granuloma, or acid fast bacilli. Immunohistochemical staining showed a combined T-cell (CD3+, CD4+) and B-cell (CD19+, CD20+) phenotype. CONCLUSION: We suggest a novel IRAE of ustekinumab, with full radiological and immunopathological iconography, which may be mediated by the complex interaction between different immunological processes.

Drugs in the treatment of obesity: sibutramine, orlistat and rimonabant.

BACKGROUND: Modification of lifestyle is the main therapeutical approach in the treatment of obesity, but use to fail on long terms of time. Addition of anti-obesity drugs allows keeping the weight loss during years and improving obesity-related comorbidities. METHODS: This review is an actualisation on efficacy, safety and tolerability of the approved drugs on the long-term treatment of obesity (orlistat and sibutramine). New indications and effects of their use far beyond the weight loss are as well commented. Finally, potential benefits of the administration of CB1 antagonist rimonabant on the weight loss and cardiometabolic risk factors are analysed in detail. DISCUSSION: A decade of experience on the use of orlistat and sibutramine has demonstrated their higher efficacy on the weight loss when compared to placebo either on adult or teenage population as well as safety and tolerability on long-term administration. Beneficial effects on the lipid profile, glycosilated haemoglobin on diabetic patients, blood pressure and levels of inflammatory cytokines, contribute to decrease the cardiovascular risk on obese patients. Phase III clinical trials using rimonabant show additional benefits to the expected weight loss, mainly reducing visceral fat and cardiometabolic risk factors. CONCLUSION: Pharmacological treatment of obesity must be considered as a therapeutical tool that has to be used together with long-term lifestyle changes, contributing to the body weight reduction as well as to the improvement of the cardiometabolic risk related to obesity.