1,720,963 research outputs found

    Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing

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    : Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the "Hallmarks of ageing". Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition

    Recurrent laryngeal nerve monitoring by flexible laryngoscopy during thyroid radiofrequency ablation in the awake patient

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    Objective: Although radiofrequency ablation (RFA) is a safe and effective non-surgical treatment for benign thyroid nodules, injury to the recurrent laryngeal nerve (RLN), is a potential and feared complication. Intermittent voice checks have been proposed to monitor vocal cord (VC) function during RFA, but such assessment is highly subjective and effort-dependent. Methods: We are here reporting the methodological use of flexible laryngoscopy (FL) for VC monitoring during bilateral thyroid RFA treatment. The patient, a 35-year-old woman, was referred to the Endocrinology Unit for subclinical hyperthyroidism due to bilateral autonomously functioning thyroid nodules. Results: At the end of the treatment of the first nodule, the FL performed by an otorhinolaryngologist specialist allowed evaluating VC function and ruling out possible paralysis before proceeding with the contralateral RFA treatment. The patient was awake during the entire procedure and well tolerated the laryngoscopic examination. The TSH serum evaluations performed one month and 9 months after the procedure assessed an euthyroid state (TSH 3.2 mIU/L and 2.8 mIU/L, respectively). Conclusion: During bilateral thyroid RFA the use of FL for VC monitoring treatment resulted in a safe, easy-to-perform, and effective strategy to minimize and anticipate RLN injury risk in the awake patient. The prevention of RLN damage is advisable in the case of single RFA treatment, while it should be strongly recommended when RFA is performed on bilateral nodules

    Proficiency in performing radiofrequency ablation procedure for non-functioning benign thyroid nodules: a qualitative rather than quantitative matter

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    Objective: Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC) required to achieve proficiency are still lacking. Materials and methods: The first 179 RFA procedures performed by a single operator in patients with non-functioning BTN were retrospectively analyzed. Six-month nodule volume reduction rate (VRR) >= 50% was regarded as reflection of proficiency. Multiple linear regression analysis has been performed to determine the relationship between the VRR and clinical variables. Cumulative sum (CUSUM) charts were plotted to assess LCs for all consecutive procedures and in relation to basal nodule size. In details, Group 1 (G1): 57 patients with small nodules ( 25 ml). Results: LC of all 179 procedures showed 3 phases: initial learning (1-39 procedures); consolidation (40-145 procedures); and experienced period (146-179 procedures). For G1 and G2 proficiency is achieved starting from the 10th procedure within the group (or 37th considering consecutively all procedures) and from the 59th procedure within the group (or 116th considering consecutively all procedures), respectively. LC of G3 did not detect operator proficiency. Conclusion: Specific LCs exist concerning the basal size of the nodule treated with RFA. In nodules with baseline volume > 25 ml suboptimal VRR has to be expected. Previously achieved experience on small-intermediate nodules does not seem to provide advantages in terms of higher VRR in the treatment of large nodules. Other potential and non-modifiable factors likely play a key role in the final volume reduction independently from the increased skill of the operator

    Do PFCAs drive the establishment of thyroid cancer microenvironment? Effects of C6O4, PFOA and PFHxA exposure in two models of human thyroid cells in primary culture

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    Background: Exposure to environmental pollutants is suspected to be one of the potential causes accounting for the increase in thyroid cancer (TC) incidence worldwide. Among the ubiquitous pollutants, per-polyfluoroalkyl substances (PFASs), were demonstrated to exert thyroid disrupting effects. Perfluoroalkyl carboxylates (PFCAs) represent a subgroup of PFAS and include perfluoro carboxylic acids (PFOA and PFHxA) and perfluoropolyether carboxylic acid (C6O4).The potential relationship between exposure to PFCAs and TC was not yet fully elucidated.This in vitro study investigated whether certain PFCAs (C6O4, PFOA, and PFHxA) can influence the composition of TC microenvironment. Methods: Two models of normal thyroid cells in primary cultures: Adherent (A-NHT) and Spheroids (S-NHT) were employed. A-NHT and S-NHT were exposed to C6O4, PFOA or PFHxA (0; 0.01; 0.1, 1; 10; 100; 1000 ng/mL) to assess viability (WST-1 and AV/PI assay), evaluate spherification index (SI) and volume specifically in S-NHT. CXCL8 and CCL2 (mRNA and protein), and EMT-related genes were assessed in both models after exposure to PFCAs. Results: PFHxA reduced the viability of both A-NHT and S-NHT. None of the PFCAs interfered with the volume or spherification process in S-NHT. CXCL8 and CCL2 mRNA and protein levels were differently up-regulated by each PFCAs, being PFOA and PFHxA the stronger inducers. Moreover, among the tested PFCAs, PFHxA induced a more consistent increase in the mRNA levels of EMT-related genes. Conclusions: This is the first evaluation of the effects of exposure to PFCAs on factors potentially involved in establishing the TC microenvironment. PFHxA modulated the TC microenvironment at three levels: cell viability, pro-tumorigenic chemokines, and EMT-genes. The results provide further evidence of the pro-tumorigenic effect of PFOA. On the other hand, a marginal effect was observed for C6O4 on pro-tumorigenic chemokines

    Redefining Thyroid Nodule Evaluation: Demographics, Misleading Symptoms, and Diagnostic Challenges. Insights From a Multicenter Study

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    Objective: Thyroid ultrasound (US) is the cornerstone for diagnosing nodular thyroid disease, yet many US examinations are prompted by nonspecific local symptoms (LS) like dysphagia or a palpable neck mass (NM). The clinical utility of such referrals remains debated. Methods: This multicenter retrospective study analyzed 614 patients diagnosed with thyroid nodules (TNs) via US from 2 endocrinology centers in Italy between December 2021 and October 2022. Patients were grouped based on referral reason: symptomatic TNs, further subdivided into NM and LS, versus nonsymptomatic TNs. Clinical, ultrasonographic, and management data were compared. Results: Symptomatic TNs accounted for 28.7% of cases (19.2% NM, 9.5% LS). NM patients were younger, more often female, and had larger, often cystic or isthmic-located nodules than nonsymptomatic TN patients. Conversely, LS patients had no significant differences in thyroid volume or nodule size but showed a higher prevalence of gastroesophageal reflux disease. Fine-needle aspiration was more common in the NM group because of larger nodules, but malignancy rates did not differ across groups. Surgical rates were similar, whereas thermal ablation was more frequent in the NM group. Conclusions: A third of TNs are diagnosed during US prompted by LS, yet only NMs are associated with distinct nodule characteristics. Dysphagia and dysphonia were nonspecific and more related to gastroesophageal reflux disease than TNs. These findings support caution against overuse of US. Demographics, nodule features, and location should guide clinical suspicion and imaging decisions to avoid unnecessary imaging and interventions

    Maximal stiffness evaluation by real-time ultrasound elastography, an improved tool for the differential diagnosis of thyroid nodules

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    Objective: The aim of the study was to evaluate the diagnostic performance of a new ultrasound elastography (USE) parameter based on the measurement of the percentage of maximal stiffness within a nodule as compared with the already established elastographic strain index (SI) and to investigate their diagnostic performance according to nodule size. Methods: The study included 218 nodules. Each nodule underwent conventional ultrasound (US), USE evaluation, and fine-needle aspiration cytology (FNAC). Thyroid nodules were further stratified into 4 subgroups (G) according to their size (G1, 3 cm). USE evaluation comprised the measurement of the percentage of the areas included in the region of interest corresponding to the maximal stiffness (% Index) and of the SI. Results: The % Index and of the SI were significantly higher in malignant than in benign thyroid nodules, and both measurements displayed a good diagnostic performance (SI sensitivity and specificity, 0.66 and 0.90, respectively; % Index sensitivity and specificity, 0.76 and 0.89, respectively). Compared with SI, the % Index was more informative, both in the whole group of thyroid nodules (odds ratio [OR], 18.68; 95% confidence interval [CI], 6.06 to 63.49; P<.0001 versus OR, 26.15; 95% CI, 8.01 to 102.87; P<.0001, respectively) and in the G1 and G2 subgroups. Conclusion: The % Index is a stronger predictor of nodule malignancy than both the SI and the conventional US signs. This is particularly true in nodules smaller than 1 cm, which are more difficult to explore both by conventional US and FNAC

    Unexplained Hyperthyrotropinemia: A Biochemical and Clinical Challenge

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    Background: A raised serum TSH in the absence of a clear etiology, or &ldquo;unexplained hyperthyrotropinemia&rdquo; (UH), can be challenging for clinicians. The aim of the present study was to evaluate potential strategies aimed at a clinical and biochemical characterization of UH patients. Methods: We compared 36 patients with UH with a control group of 14 patients with chronic autoimmune thyroiditis (CAT) and subclinical hypothyroidism. The two groups were compared in terms of the following: (i) the rate of normalization of TSH after repeating with another assay; (ii) the rate of normalization of TSH over time with the same assay; (iii) the reduction in TSH after precipitation with polyethilenglycole (PEG); and (iv) free thyroxine (FT4) levels. Results: Similar TSH levels were observed in UH [5.65 (5.21&ndash;6.37)] and CAT [5.62 (5.17&ndash;8.50)] (p = 0.489). TSH measurement with another assay method showed a normal TSH value in 41.9% of UH vs. 46.1% of CAT patients (p = 0.797). After repeating the TSH measurement in time with the same assay method, an increased TSH value was confirmed in all cases, in both groups (0% in the UH group vs. 0% in the CAT group, p = 1.000). TSH recovery after PEG precipitation was similar in the two groups (% precipitable post-PEG: 68.75 &plusmn; 3.14 in UH vs. 68.67 &plusmn; 7.18 in CAT, p = 0.960). FT4 levels were similar in the two groups (FT4 1.02 &plusmn; 0.20 ng/dl in UH vs. 1.00 &plusmn; 0.20 ng/dl in CAT, p = 0.789). Conclusions: The results do not support the concept that laboratory interferences are more frequent in UH patients, suggesting that patients with UH should be managed in the same way as patients with CAT until proven otherwise

    The American Thyroid Association risk classification of papillary thyroid cancer according to presurgery cytology

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    Objective: To compare the American Thyroid Association (ATA) risk staging of histologically proven papillary thyroid cancer (PTC) in patients who received a presurgery cytologic result of either indeterminate thyroid nodules (ITNs, Bethesda III/IV) or suspicious for malignancy/malignant (TIR 4/5, Bethesda V/VI). Methods: Clinical, ultrasonographic, cytological data from patients with histologically diagnosed PTC were retrospectively collected. Results: Patients were stratified according to the preoperative fine-needle aspiration cytology into 2 groups: 51 ITNs (TIR3A/3B) and 118 suspicious/malignant (TIR 4/5). Male/female ratio, age, and presurgery TSH level were similar between the 2 groups. At ultrasound, TIR 4/5 nodules were significantly more frequently hypoechoic (P = .037), with irregular margins (P = .041), and with microcalcifications (P = .020) and were more frequently classified as high-risk according to the European Thyroid Imaging and Reporting Data System (EU-TIRADS; P = .021). At histology, the follicular PTC subtype was significantly more prevalent among ITNs while classical PTC subtype was more frequent in TIR 4/5 group (P = .002). In TIR 4/5 group, a higher rate of focal vascular invasion (P < .001) and neck lymph node metastasis (P = .028) was observed. Intermediate-risk category according to ATA was significantly more frequent in TIR 4/5 group while low-risk category was more frequently found among ITNs (P = .021), with a higher number of patients receiving radioiodine in TIR 4/5 group (P = .002). At multivariate logistic regression, having a TIR 4/5 cytology was associated with a significant risk of having a higher ATA risk classification as compared to ITN (OR 4.6 [95% CI 1.523-14.007], P = .007), independently from presurgery findings (nodule size at ultrasound, sex, age, and EU-TIRADS score). Conclusions: Papillary thyroid cancers recorded among ITNs are likely less aggressive and are generally assessed as at lower risk according to ATA classification

    Differences and analogies in thyroid cancer discovered incidentally or by thyroid related screening: A multicenter study

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    Objective: The prevalence of thyroid cancer (TC) has increased worldwide, and an association with metabolic and cardiovascular disorders has been reported. Moreover, an increasing percentage of patients are currently diagnosed incidentally through non-thyroid-related imaging for other clinical conditions. Our aim was to assess the prevalence of thyroid-related disease (TD) versus incidental diagnosis (ID) pre-surgery reasons leading to TC diagnosis and to compare the two groups in terms of clinical characteristics, size and severity of TC at presentation and rate of non-thyroid cancers and cardiovascular/metabolic comorbidities. Design: We performed a retrospective cohort study in three high-volume hospital-based centers for thyroid diseases (Pavia, Latina and Messina) in Italy. Patients: Consecutive patients with TC were included. Measurements: Data on pre-surgery reasons leading to TC diagnosis, age, sex, BMI, presence of cardiometabolic comorbidities and non-thyroid cancer were collected. Results: Among the 327 enrolled subjects, the diagnosis of TC was prompted by thyroid-related reasons in 262 (80.1%, TD group) and incidental in 65 (19.9%, ID group). The ID group patients were more frequently males, significantly older and with a higher BMI than the TD group ones; they had a higher rate of non-thyroidal cancers and cardiovascular/metabolic comorbidities. No significant differences could be observed in terms of TC histotype, cancer size, extrathyroidal extension, lymph node metastases, AJCC staging or American Thyroid Association (ATA) risk stratification. Conclusions: Biological features of TC are similar in the TD and ID groups, but patients in the two groups display significant differences regarding their clinical features
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