Search

BackgroundPrevious studies have shown increased risk of fracture in older patients with poor or strict glycemic control (glycated hemoglobin, HbA1c, ≥ 8% or < 6-7% respectively); however, these reports did not investigate the oldest-old population. Comprehensive geriatric assessment (CGA) and a patient-centered approach have been proven to improve the quality of care in the management of Type 2 Diabetes Mellitus (T2DM) in the older patients, but data regarding T2DM in patients with fragility fractures are still lacking.AimTo investigate the prognostic role of HbA1c and frailty level in older diabetic patients admitted for hip fracture.MethodsProspective observational cohort study conducted on diabetic geriatric patients consecutively hospitalized for hip fracture in the orthogeriatric unit of a tertiary care hospital. Preoperative comprehensive geriatric assessment (CGA) was performed. Using the Clinical Frailty Scale (CFS), diabetic patients were categorized in robust (CFS < 5) and frail (CFS ≥ 5), and further stratified according to HbA1c values [Tertile 1 (T1) HbA1c < 48 mmol/mol, Tertile 2 (T2) 48-58 mmol/mol and Tertile 3 (T3) > 58 mmol/mol). Comparisons between continuous variables were performed with analysis of non-parametric test for independent samples, while relationships between categorical variables were assessed by chi-square test. Using logistic multivariate regression, we evaluated the determinants of 1-year all-cause mortality in diabetic older patients with hip fracture.ResultsAmong the 1319 older patients (mean age 82.8 ± 7.5 years, 75.9% females) hospitalized for hip fracture, 204 (15.5%) had a previous diagnosis of T2DM. T2DM patients showed an increased proportion of multiple concurrent fractures occurred during the accidental fall or syncope (12.7% vs 11.2%, p=0.02). One-year mortality after hip fracture surgery was significantly higher in T2DM as compared to not diabetic patients (21.2% vs 12.5%, pvs 5%, p=0.001 for T2 and 43.5% vs 13.3%, p=ConclusionsFrail patients with HbA1c ≥ 48 mmol/L showed an increased mortality risk as compared to robust counterparts. CFS represents an important tool to select diabetic subjects with higher likelihood of adverse outcome.

Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis. The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF receptor-2 [VEGFR-2] and hypoxia-inducible factor-1α [HIF-1α] genes or their genetic interactions with the risk of nodular goiter development. 116 normal subjects, without any thyroid disease, and 108 subjects with nodular goiter [subjects with goiter and at least one thyroid nodule of > 1 cm of maximum size and in absence of signs of autoimmunity] were selected from a homogeneous population living in a mild iodine deficiency geographic area. Analyses were performed on germline DNA obtained from blood samples and VEGF-A rs3025039, VEGFR-2 rs2071559, and HIF-1αrs11549465 SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction [MDR] methodology was applied to investigate the genetic interaction between SNPs. Hardy–Weinberg equilibrium was performed. None of the studied polymorphisms were individually associated with a higher risk to develop nodular goiter [P > 0.05]. The combination of the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms had the highest accuracy of 0.58 [P = 0.018] and the interaction of some genotypes was significantly associated with the risk of nodular goiter development. Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Thyroid nodules are common in the general population and vary widely in their propensity to harbor thyroid malignancies. The category of follicular lesion of undetermined significance, for instance, carries only a 15% risk of malignancy. The overarching aim of this work was the proteomic study of thyroid cancer because more effort needs to be placed on differentiating malignant thyroid nodules to avoid unnecessary thyroidectomy. We used 2-dimensional electrophoresis coupled to nano-liquid chromatography electrospray ionization tandem mass spectrometry, to examine fine-needle aspiration (FNA), which was easily attainable from the wash of the syringe used for classical FNA biopsy. Overall, we found 25 different proteins able to discriminate benign from malignant samples. The different expression of moesin; annexin A1 (ANXA1); cornulin (CRNN); lactate dehydrogenase; enolase; protein DJ-1; and superoxide dismutase was confirmed in FNA by enzyme-linked immunosorbent assay or Western blot. Receiver operating characteristic curves were calculated to investigate the discriminative power of our marker. The best performance in diagnosis was obtained by combining ANXA1, enolase, protein DJ-1, superoxide dismutase, and CRNN. In addition, the most highly ranked proteins, from the perspective of follicular lesion of undetermined significance, were ANXA1 and CRNN. The research of these candidate biomarkers has then been widened to other biological fluids, such as serum and whole saliva. In conclusion, we believe that when a decision by a thyroid nodule biopsy cannot be distinctly made, the combination of our biomarkers may be one of the criteria to be taken into account for the final decision, together with the identification of ANXA1 in serum and saliva.

ObjectiveMicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules.DesignIn this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA.MethodsThe prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed.ResultsUsing data mining techniques, we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155, and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false-positive and six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules.ConclusionsThe expression profiles of three miRNAs allowed us to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology, a low sensitivity and specificity despite the low number of false-negative predictions was obtained, limiting the practical interest of the method.

Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from malignant thyroid nodules. However, cytological analysis cannot always allow a proper diagnosis. We believe that the improvement of the diagnostic capability of pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we performed a proteome analysis to examine FNA collected after thyroidectomy. With the present study, we examined the applicability of these results on pre-surgical FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a correct comparison with our previous results, we processed only benign (n = 114), papillary classical variant (cPTC) (n = 34) and papillary tall cell variant (TcPTC) (n = 14) FNA. We evaluated levels of five proteins previously found up-regulated in thyroid cancer with respect to benign nodules. ELISA and western blot (WB) analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB), Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid nodules may help to distinguish benign versus malignant thyroid nodules. Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and specificity obtained from ROC curve analysis.