Objective: The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are ...implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT. Design and methods: A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD−; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up. Results: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD− group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases. Conclusions: In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.
To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between CKD-mineral bone disorder biomarkers and vascular stiffness (Cardio Ankle ...Vascular Index, CAVI) in the course of type 2 diabetes (T2DM).
we evaluated 174 T2DM patients (median age 56 y; M/F = 100/74) with diabetes duration less than 10 years and without decreased glomerular filtration rate (eGFR ≥60 ml/min/1.73 m 2) or macrovascular complications. Thirty-four age matched healthy subjects (M/F: 13/21; age: 53.550.0-57.7 y.o; eGFR 107.597.0-119.7) ml/ml/min1.73m2) served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers.
albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g 5.6-17.2 with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy (DN). Serum parathyroid hormone, Fibroblast Growth Factor 23 and Sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (p<.001), Hb1A1c (p=.036), systolic (p=.021) and diastolic blood pressure (DBP) (p=.001) and negatively with 25D (p=.046). In multivariate analysis, age, DBP, ACR, and s-Klotho were independent positive predictors of CAVI.
in the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP, and ACR are modifiable risk factors of vascular stiffness in T2DM thus warranting optimal assessment.
Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3-7%. Germline mutations in the aryl-hydrocarbon receptor (AHR) ...interacting protein (AIP) have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC) in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer.
Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied.
12 DTCs (10 papillary and 2 follicular carcinomas) were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status.
The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available ...about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS. Materials and methods Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n = 48) were also matched against a population of men with treated secondary hypogonadism (n = 21). Results Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (p < 0.01), increased intima-media thickness (p < 0.05) (− 34% and + 42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, p < 0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism. Conclusion Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5–10% of all patients with end-stage ...kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss. Methods We evaluated kidney function by estimated glomerular filtration rate (eGFR) in 32 ADPKD patients in different stages of kidney disease at T0 and after a 24-month follow up (T1). Patients were divided into two groups: Rapid disease progression (RP, n 15) and Non-rapid disease progression (NRP, n 17), according to the Mayo Clinic classification criteria. At T0, ADPKD patients underwent plasma sampling for quantitative analysis of h-miR-17-5p, h-miR-21-5p and h-miR-199a-5p microRNA expression, using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) method and a 3 T magnetic resonance imaging (MRI), using an advanced MRI imaging protocol, for the quantification of total kidney volume (TKV), total perfusion volume (TPV) and total fibrotic volume (TFV). Results The expression of h-miR17-5p was higher ( p < 0.05) in ADPKD patients with rapid disease progression. h-miR-17-5p, h-miR-21-5p and h-mir-199-5p showed a positive and significant correlation with the eGFR slope (mL/min/1.73 m 2 /year) ( p < 0.05) but not with the eGFR at both T0 and T1. Both total fibrotic volume (cm 3 ) and height-adjusted total fibrotic volume (cm 3 /m) were positively and significantly correlated to h-miR 21-5p and h-miR 199-5p ( p < 0.05), but not to total kidney volume (cm 3 ) and height-adjusted total kidney volume (cm 3 /m). Conclusions The microRNAs we studied were associated with fibrosis and renal damage, suggesting their possible role as biomarkers able to identify ADPKD patients at high risk of disease progression regardless of the degree of kidney function, and therefore suitable for medical therapy, and may help uncovering new molecular mechanisms underlying cystogenesis. Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis ...investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity.
Material and methods
Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment.
Results
Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses.
Conclusion
No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Not all conceivable grammars are realized within human languages. Rules based on
rigid distances, in which a certain word must occur at a fixed distance from another word, are never found in grammars ...of human languages. Distances between words are specified in terms of relative,
non-rigid positions. The left inferior frontal gyrus (IFG) (Broca's area) has been found to be involved in the computation of non-rigid but not of rigid syntax in the language domain. A fundamental question is therefore whether the neural activity underlying this non-rigid architecture is language-specific, given that analogous structural properties can be found in other cognitive domains. Using event-related functional magnetic resonance imaging (fMRI) in sixteen healthy native speakers of Italian, we measured brain activity for the acquisition of rigid and non-rigid syntax in the visuo-spatial domain. The data of the present experiment were formally compared with those of a previous experiment, in which there was a symmetrical distinction between rigid and non-rigid syntax in the language domain. Both in the visuo-spatial and in the language domain, the acquisition of non-rigid syntax, but not the acquisition of rigid syntax, activated Brodmann Area 44 of the left IFG. This domain-independent effect was specifically modulated by performance improvement. Thus, in the human brain, one single “grammar without words” serves different higher cognitive functions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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