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OBJECTIVE: Incidental diagnosis of thyroid nodules, and therefore of thyroid cancer, has definitely increased in recent years, but the mortality rate for thyroid malignancies remains very low. Within this landscape of overdiagnosis, several nodule ultrasound scores (NUS) have been proposed to reduce unnecessary diagnostic procedures. Our aim was to verify the suitability of five main NUS. METHODS: This single-center, retrospective, observational study analyzed a total number of 6474 valid cytologies. A full clinical and US description of the thyroid gland and nodules was performed. We retrospectively applied five available NUS: KTIRADS, ATA, AACE/ACE-AME, EUTIRADS, and ACRTIRADS. Thereafter, we calculated the sensitivity, specificity, PPV, and NPV, along with the number of possible fine-needle aspiration (FNA) sparing, according to each NUS algorithm and to clustering risk classes within three macro-groups (low, intermediate, and high risk). RESULTS: In a real-life setting of thyroid nodule management, available NUS scoring systems show good accuracy at ROC analysis (AUC up to 0.647) and higher NPV (up to 96%). The ability in FNA sparing ranges from 10 to 38% and reaches 44.2% of potential FNA economization in the low-risk macro-group. Considering our cohort, ACRTIRADS and AACE/ACE-AME scores provide the best compromise in terms of accuracy and spared cytology. CONCLUSIONS: Despite several limitations, available NUS do appear to assist physicians in clinical practice. In the context of a common disease, such as thyroid nodules, higher accuracy and NPV are desirable NUS features. Further improvements in NUS sensitivity and specificity are attainable future goals to optimize nodule management. KEY POINTS: ⢠Thyroid nodule ultrasound scores do assist clinicians in real practice. ⢠Ultrasound scores reduce unnecessary diagnostic procedures, containing indolent thyroid microcarcinoma overdiagnosis. ⢠The variable malignancy risk of the "indeterminate" category negatively influences score's performance in real-life management of thyroid lesions.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Algoritmos , Biopsia con Aguja Fina , Humanos , Estudios Retrospectivos , Neoplasias de la Tiroides/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico por imagen , UltrasonografíaRESUMEN
Bone morphogenetic protein 15 (BMP15) encodes an oocyte factor with a relevant role for folliculogenesis as homodimer or cumulin heterodimer (BMP15-GDF9). Heterozygous BMP15 variants in the precursor or mature peptide had been associated with primary ovarian insufficiency (POI), but the underlying mechanism remains elusive and a double dose of BMP15 was suggested to be required for adequate ovarian reserve. We uncovered two homozygous BMP15 null variants found in two girls with POI and primary amenorrhea. Both heterozygous mothers reported physiological menopause. We then performed western blot, immunofluorescence, and reporter assays to investigate how previously reported missense variants, p.Y235C and p.R329C, located in the precursor or mature domains of BMP15, may affect protein function. The p.R329C variant demonstrates an impaired colocalization with growth/differentiation factor 9 (GDF9) at confocal images and diminished activation of the SMAD pathways at western blot and reporter assays in COV434 follicular cell line. In conclusion, BMP15 null mutations cause POI only in the homozygous state, thus discarding the possibility that isolated BMP15 haploinsufficiency can cause evident ovarian defects. Alternatively, heterozygous BMP15 missense variants may affect ovarian function by interfering with cumulin activity. Our data definitely support the fundamental role of BMP15 in human ovarian folliculogenesis.
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Proteína Morfogenética Ósea 15/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Mutación Missense , Folículo Ovárico/metabolismo , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/genética , Adolescente , Alelos , Línea Celular , Hibridación Genómica Comparativa , Consanguinidad , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética/métodos , Genotipo , Homocigoto , Humanos , Folículo Ovárico/crecimiento & desarrollo , Linaje , Fenotipo , Insuficiencia Ovárica Primaria/metabolismo , Eliminación de SecuenciaRESUMEN
Cell-free DNA (cfDNA) quantity and quality in plasma has been investigated as a non-invasive biomarker in cancer. Previous studies have demonstrated increased cfDNA amount and length in different types of cancer with respect to healthy controls. The present study aims to test the hypothesis that the presence of longer DNA strands circulating in plasma can be considered a biomarker for tumor presence in thyroid cancer. We adopted a quantitative real-time PCR (qPCR) approach based on the quantification of two amplicons of different length (67 and 180 bp respectively) to evaluate the integrity index 180/67. Cell-free DNA quantity and integrity were higher in patients affected by nodular thyroid diseases than in healthy controls. Importantly, cfDNA integrity index was higher in patients with cytological diagnosis of thyroid carcinoma (Thy4/Thy5) than in subjects with benign nodules (Thy2). Therefore, cfDNA integrity index 180/67 is a suitable parameter for monitoring cfDNA fragmentation in thyroid cancer patients and a promising circulating biomarker in the diagnosis of thyroid nodules.
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Biomarcadores de Tumor , Ácidos Nucleicos Libres de Células , ADN de Neoplasias , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Fragmentación del ADN , Femenino , Humanos , Biopsia Líquida , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Adulto JovenRESUMEN
PURPOSE: Cabozantinib is an oral multi-tyrosine kinase inhibitor (TKI) that has been approved in Europe for advanced renal cell carcinoma, hepatocellular carcinoma, locally advanced and metastatic medullary thyroid carcinoma (MTC) and radioiodine-refractory differentiated thyroid cancer. Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous malignant neuroendocrine tumour that usually presents in sun-exposed skin areas of immunosuppressed patients. Conflicting data exist about cabozantinib for MCC and this TKI is currently under investigation in several onco-endocrine frameworks. METHODS: We herein report a case of an 83-year-old man who was diagnosed with MCC during the treatment of an advanced metastatic MTC. The diagnosis of MCC was established based on clinical, histopathologic evaluation and immunohistochemistry. A systematic review of the literature on cabozantinib use for advanced endocrine and neuroendocrine tumours has been performed. RESULTS: The patient was initially treated with surgery and adjuvant radiotherapy. Cabozantinib was therefore started to control both MTC and MCC. After 24 months, no sign of local or metastatic MCC relapse was evidenced. CONCLUSION: Promising data on cabozantinib treatment for endocrine and neuroendocrine neoplasms is recently emerging in the literature. In our clinical case, we reported that, besides the good response for the MTC, cabozantinib also seems to effectively control metastatic MCC, along with efficient surgery and adjuvant radiotherapy. Further investigations are needed to determine the efficacy and safety of cabozantinib in MCC patients and in off-label endocrine tumours.
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Anilidas , Carcinoma Neuroendocrino , Piridinas , Neoplasias de la Tiroides , Masculino , Humanos , Anciano de 80 o más Años , Radioisótopos de Yodo/uso terapéutico , Recurrencia Local de Neoplasia , Carcinoma Neuroendocrino/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patologíaRESUMEN
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.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Femenino , Masculino , Estados Unidos , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/cirugía , Estudios Retrospectivos , Radioisótopos de Yodo , Nódulo Tiroideo/patología , Ultrasonografía/métodosRESUMEN
CONTEXT: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management. OBJECTIVE: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone. DESIGN: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database. PATIENTS: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies. INTERVENTIONS: Serum Tg levels assessed at 1-year follow-up visit. MAIN OUTCOME MEASURE: Detection of structural disease within 5 years of follow-up. RESULTS: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease. CONCLUSIONS: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA.
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Introduction: Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. Methods: A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Results: Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Conclusion: Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.
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The sporadic parathyroid pathology of surgical interest is primarily limited to lesions that are the cause of hormonal hyperfunction (primary hyperparathyroidism). In recent years, parathyroid surgery has evolved significantly, and numerous minimally invasive parathyroidectomy techniques have been developed. In this study, we describe a single-center and well-documented case series of sporadic primary hyperparathyroidism, surgically treated by a single operator in the Endocrine Surgery Unit of the Surgical Clinic of the University of Florence-Careggi University Hospital, recorded and updated in a dedicated database that embraces the entire evolutionary timeframe of parathyroid surgery. From January 2000 to May 2020, 504 patients with a clinical and instrumental diagnosis of hyperparathyroidism were included in the study. The patients were divided into two groups, based on the application of intraoperative parathyroid hormone (ioPTH). The analysis shows that the use of ioPTH with the rapid method could be ineffective in helping surgeons in primary operations, especially when ultrasound and scintiscan are concordant. The advantages obtained by not using intraoperative PTH are not only economic. In fact, our data shows shorter operating and general anesthesia times and hospital stays, having an important impact on patient biological commitment. Furthermore, the significant reduction in operating time makes it possible to almost triple the volume of activity in the same unit of time available, with an undeniable advantage for the reduction of waiting lists. In recent years, minimally invasive approaches have allowed surgeons to reach the best compromise between invasiveness and aesthetic results.
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Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+/K+-adenosine triphosphatase (H+/K+-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+/K+-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+/K+-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+/K+-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+/K+-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.
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Autoinmunidad , Gastritis , Células Th17 , Adenosina Trifosfatasas , Autoinmunidad/inmunología , Citocinas , Mucosa Gástrica , Gastritis/diagnóstico , Gastritis/inmunología , ATPasa Intercambiadora de Hidrógeno-Potásio , Humanos , Interleucina-17RESUMEN
Context: Despite the wide revision of current guidelines, the management of papillary thyroid microcarcinoma (mPTC) still has to be decided case by case. There is conflicting evidence about the role of more frequent histological subtypes, and no data about potential differences at presentation. Objective: Our aim was to compare the phenotype of the 2 most frequent mPTC variants, namely, classical papillary thyroid microcarcinoma (mPTCc) and the follicular variant of papillary thyroid microcarcinoma (mFVPTC) . Methods: Retrospective observational study, from January 2008 to December 2017 of a consecutive series of patients with mPTCc and mFVPTC. All cases were classified according to the 2015 American Thyroid Association (ATA) risk classification. Clinical and preclinical features of mPTCc and mFVPTC at diagnosis were collected. The comparison was also performed according to the incidental/nonincidental diagnosis and differences were verified by binary logistic analysis. Results: In total, 235 patients were eligible for the analysis (125 and 110 mPTCc and mFVPTC, respectively). Compared with mPTCc, mFVPTCs were more often incidental and significantly smaller (4 vs 7â mm) (P < .001 all), possibly influenced by the higher rate of incidental detection. mFVPTC and incidental (P < .001 both) tumors were significantly more often allocated within the low-risk class. A logistic regression model, with ATA risk class as the dependent variable, showed that both mFVPTC (OR 0.465 [0.235-0.922]; P = .028]) and incidental diagnosis (OR 0.074 [0.036-0.163]; P < .001) independently predicted ATA risk stratification. Conclusion: mFVPTC shows some differences in diagnostic presentation compared with mPTCc, and seems to retain a significant number of favorable features, including a prevalent onset as incidental diagnosis.
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Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both autoantibodies (e.g. intrinsic factor (IFA) antibodies and anti parietal cell (PCA) antibodies and autoreactive T cells specific for IFA and the parietal cell proton pump ATPase. Iron deficient anemia (IDA) is a microcytic anemia and represents the most common cause of anemia worldwide. Our work aimed to investigate serum levels of several interleukins (IL) of the IL-20 cytokine subfamily in patients with PA, with IDA and in healthy subjects (HC). We compared serum levels of IL-19, IL-20, IL-26, IL-28A and IL-29 in 43 patients with PA and autoimmune gastritis, in 20 patients with IDA and no autoimmune gastritis, and in 47 HC. Furthermore, we analyzed the IL-19 cytokine production by gastric lamina propria mononuclear cells (LPMC) in eight patients with PA and four HC. We found that patients with PA have significantly higher serum levels of IL-19 (163.68 ± 75.96 pg/ml) than patients with IDA (35.49 ± 40.97 pg/ml; p<0.001) and healthy subjects (55.68 ± 36.75 pg/ml; p<0.001). Gastric LPMC from all PA patients were able to produce significantly higher levels of IL-19 (420.67 ± 68.14 pg/ml) than HC (53.69 ± 10.92 pg/ml) (p<0.01). Altogether, our results indicate that IL-19 serum levels are significantly increased in patients with PA but not with IDA and that IL-19 is produced in vivo in the stomach of PA patients. These data open a new perspective on PA pathogenesis and suggest that IL-19 may represent a novel important tool for the management of patients with PA.
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Anemia Perniciosa , Anemia , Gastritis , Anemia Perniciosa/etiología , Autoanticuerpos , Citocinas , Gastritis/complicaciones , Humanos , InterleucinasRESUMEN
BACKGROUND: The diagnosis of thyroid cancer is continuously increasing and consequently the amount of thyroidectomy. Notwithstanding the actual surgical skill, postoperative hypoparathyroidism still represents its most frequent complication. The aims of the present study are to analyze the rate of postoperative hypoparathyroidism after thyroidectomy, performed for cancer by a single first operator, without any technological aid, and to compare the data to those obtained adopting the most recent technological adjuncts developed to reduce the postoperative hypoparathyroidism. METHODS: During the period 1997-2020 at the Endocrine Surgery Unit of the Department of Clinical and Experimental Medicine of the University of Florence, 1648 consecutive extracapsular thyroidectomies for cancer (401 with central compartment node dissection) were performed. The percentage of hypoparathyroidism, temporary or permanent, was recorded both in the first period (Group A) and in the second, most recent period (Group B). Total thyroidectomies were compared either with those with central compartment dissection and lobectomies. Minimally invasive procedures (MIT, MIVAT, some transoral) were also compared with conventional. Fisher's exact and Chi-square tests were used for comparison of categorical variables. p < 0.01 was considered statistically significant. Furthermore, a literature research from PubMed® has been performed, considering the most available tools to better identify parathyroid glands during thyroidectomy, in order to reduce the postoperative hypoparathyroidism. We grouped and analyzed them by technological affinity. RESULTS: On the 1648 thyroidectomies enrolled for the study, the histotype was differentiated in 93.93 % of cases, medullary in 4% and poorly differentiated in the remaining 2.06%. Total extracapsular thyroidectomy and lobectomy were performed respectively in 95.45% and 4.55%. We recorded a total of 318 (19.29%) cases of hypocalcemia, with permanent hypoparathyroidism in 11 (0.66%). In regard to the literature, four categories of tools to facilitate the identification of the parathyroids were identified: (a) vital dye; (b) optical devices; (c) autofluorescence of parathyroids; and (d) autofluorescence enhanced by contrast media. Postoperative hypoparathyroidism had a variable range in the different groups. CONCLUSIONS: Our data confirm that the incidence of post-surgical hypoparathyroidism is extremely low in the high volume centers. Its potential reduction adopting technological adjuncts is difficult to estimate, and their cost, together with complexity of application, do not allow immediate routine use. The trend towards increasingly unilateral surgery in thyroid carcinoma, as confirmed by our results in case of lobectomy, is expected to really contribute to a further reduction of postsurgical hypoparathyroidism.
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Background: One of the most widely used risk stratification systems for estimating individual patients' risk of persistent or recurrent differentiated thyroid cancer (DTC) is the American Thyroid Association (ATA) guidelines. The 2015 ATA version, which has increased the number of patients considered at low or intermediate risk, has been validated in several retrospective, single-center studies. The aims of this study were to evaluate the real-world performance of the 2015 ATA risk stratification system in predicting the response to treatment 12 months after the initial treatment and to determine the extent to which this performance is affected by the treatment center in which it is used. Methods: A prospective cohort of DTC patients collected by the Italian Thyroid Cancer Observatory web-based database was analyzed. We reviewed all records present in the database and selected consecutive cases that satisfied inclusion criteria: (i) histological diagnosis of DTC, with the exclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features; (ii) complete data of the initial treatment and pathological features; and (iii) results of 1-year follow-up visit (6-18 months after the initial treatment), including all data needed to classify the estimated response to treatment. Results: The final cohort was composed of 2071 patients from 40 centers. The ATA risk of persistent/recurrent disease was classified as low in 1109 patients (53.6%), intermediate in 796 (38.4%), and high in 166 (8.0%). Structural incomplete responses were documented in only 86 (4.2%) patients: 1.5% in the low-risk, 5.7% in the intermediate-risk, and 14.5% in the high-risk group. The baseline ATA risk class proved to be a significant predictor of structural persistent disease, both for intermediate-risk (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.59-8.43) and high-risk groups (OR 16.48; CI 7.87-34.5). Individual center did not significantly influence the prediction of the 1-year disease status. Conclusions: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability.
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Diferenciación Celular , Técnicas de Apoyo para la Decisión , Radioisótopos de Yodo/uso terapéutico , Escisión del Ganglio Linfático , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/terapia , Tiroidectomía , Adulto , Bases de Datos Factuales , Femenino , Humanos , Radioisótopos de Yodo/efectos adversos , Italia , Escisión del Ganglio Linfático/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Estudios Prospectivos , Radiofármacos/efectos adversos , Medición de Riesgo , Factores de Riesgo , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Tiroidectomía/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The intrinsic factor is the major humoral autoantigen in pernicious anemia/autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by intrinsic factor - specific gastric T cells. Aim of this study was to investigate intrinsic factor-specific T cells in the gastric mucosa of pernicious anemia patients and define their functional properties. For the first time we provide evidence that gastric mucosa of pernicious anemia patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize intrinsic factor. Most of these clones (94%) showed a T helper 17 or T helper 1 profile. All intrinsic factor-specific clones produced tumor necrosis factor-α, interleukin-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived intrinsic factor-specific T-cell clones expressed cytotoxicity against target cells. Our results indicate that activation of intrinsic factor-specific T helper 17 and T helper 1 T cells in the gastric mucosa represent a key effector mechanism in pernicious anemia suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.
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INTRODUCTION: The relationship between obesity and erectile dysfunction (ED) has not been completely clarified. AIM: The aim of this study is to investigate the association between different obesity class (the World Health Organization definition) with several hormonal and instrumental parameters, in a large sample of patients with ED. METHODS: A consecutive series of 2,435 (mean age 52.1 +/- 13.0 years) male patients with ED was investigated. MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters were studied, along with a structured interview on erectile dysfunction (SIEDY), a psychometric questionnaire (Middle Hospital Questionnaire), and penile doppler ultrasound (PDU). RESULTS: Among patients studied, 41.5% were normal weight, while 42.4%, 12.1% and 4.0% showed a BMI of 25-29.9, 30-34.9 and 35 kg/m(2 )or higher, respectively. Androgen levels (including sex hormone-binding globuline bound and unbound testosterone) decreased as a function of obesity class, while luteinising hormone levels did not show any significant change. Obesity was significantly associated with a higher organic contribution to ED (as assessed by SIEDY scale 1 score), and worse PDU parameters. At multivariate linear regression analysis, after adjustment for confounders (including metabolic syndrome), low androgens remained associated with BMI, while both basal and dynamic (after prostaglandin E1 [PGE1] stimulation) peak systolic velocity (PSV) at PDU resulted significantly associated with age and elevated blood pressure (Adj. r = -0.179, -0.285 and -0.094, -0.071 for age, hypertension and for basal and dynamic PSV, respectively; all P < 0.05). CONCLUSIONS: Obesity is characterized by low levels of androgens in men with ED, after adjustment for comorbidities. Obesity associated comorbidities, particularly hypertension, are the most important determinants of arteriogenic obesity-associated ED.
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Andrógenos/sangre , Disfunción Eréctil/sangre , Hipogonadismo/sangre , Obesidad/sangre , Análisis de Varianza , Índice de Masa Corporal , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Disfunción Eréctil/fisiopatología , Humanos , Italia/epidemiología , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/fisiopatología , Psicometría , Factores de Riesgo , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Erectile dysfunction (ED) is often associated with a wide array of psychiatric symptoms, although few studies systematically address their specific association with ED determinants. AIM: The aim of this study is to explore the relationship between ED (as assessed by SIEDY Structured Interview, a 13-item tool which identifies and quantifies the contribution of organic, relational, and intrapsychic domains of ED) and different psychopathological symptoms (as assessed by the Middlesex Hospital Questionnaire, a self-reported test for the screening of mental disorders in a nonpsychiatric setting). METHODS: A consecutive series of 1,388 (mean age 51 +/- 13 years) male patients with ED was studied. MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters were investigated, along with SIEDY Interview and the Middlesex Hospital Questionnaire. RESULTS: Psychiatric symptoms resulted differentially associated with SIEDY domains. Depressive and phobic-anxiety symptoms were associated with the relational domain, somatization with the organic one, while free-floating anxiety, obsessive-compulsive, and phobic symptoms were significantly related with higher intrapsychic SIEDY scores. In addition, relevant depressive symptomatology was associated with hypogonadism, the presence of low frequency of intercourse, hypoactive sexual desire (HSD), and conflictual relationships within the couple and the family. Patients with high free-floating anxiety symptoms were younger, and complained of an unsatisfactory work and a conflictual relationship within family. Conversely, subjects with higher phobic anxious symptoms displayed a more robust relational functioning. Similar results were observed in subjects with obsessive-compulsive symptoms, who also reported a lower prevalence of HSD. Finally, subjects with somatization symptoms showed the worst erectile function. CONCLUSIONS: The main value of this study is that it alters various clinicians' belief that many psychiatric symptoms can be found among ED patients. Systematic testing of patients with ED, through psychiatric questionnaires, is recommended to detect even slight or moderate psychopathological distresses, which specifically associate and exacerbate sexual disturbances.
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Disfunción Eréctil/epidemiología , Salud del Hombre , Trastornos Mentales/epidemiología , Calidad de Vida , Conducta Sexual/estadística & datos numéricos , Adulto , Anciano , Comorbilidad , Disfunción Eréctil/psicología , Humanos , Italia/epidemiología , Estilo de Vida , Masculino , Persona de Mediana Edad , Conducta Sexual/psicología , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The role of testosterone (T) in pathogenesis of ejaculatory symptoms has not been completely clarified. AIM: To evaluate the possible contribution of T and hypogonadism in the control of the ejaculatory reflex, comparing subjects with premature ejaculation (PE) or delayed ejaculation (DE) to those without ejaculatory dysfunction. METHODS: A consecutive series of 2,437 (mean age 51.9 +/- 13.0 years) male patients with sexual dysfunction was studied. MAIN OUTCOME MEASURE: Several hormonal and biochemical parameters were studied, along with the structured interview on erectile dysfunction (SIEDY) structured interview. Hypogonadism were defined when total testosterone (TT) was lower than 10.4 nmol/L. RESULTS: Among the patients studied, 714 (25.9%) and 121 (4.4%) reported PE and DE, respectively. In the youngest age band (25-40 years), subjects with PE reported higher TT and free testosterone (FT) levels when compared to the other groups (subjects with DE or those without PE and DE; P < 0.05 for both). Conversely, in the oldest age band (55-70 years), lower TT and FT levels were observed in DE subjects. Accordingly, patients with PE showed the lowest (12%) and subjects with DE the highest (26%) prevalence of hypogonadism. These differences were confirmed even after adjustment for confounders such as age and libido (HR = 0.75 [0.57-0.99] and 1.83 [1.14-3.94] for PE and DE, respectively; both P < 0.05). CONCLUSIONS: Our data seem to suggest that T plays a facilitatory role in the control of ejaculatory reflex. Both central and peripheral mechanisms have been advocated to explain this association. Clinical studies are currently in progress to further establish the role of T in the ejaculatory dysfunction, attempting to revert DE by androgen administration.
Asunto(s)
Eyaculación/fisiología , Hipogonadismo/sangre , Disfunciones Sexuales Fisiológicas/sangre , Testosterona/sangre , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Reflejo/fisiologíaRESUMEN
OBJECTIVE: the aim of present study is to determine possible contributions of INF-gamma inducible chemochine CXCL-10 in the thyroid color doppler ultrasound (CDU) parameters typical of autoimmune disorders. METHODS: we studied a consecutive series of 25 patients with autoimmune thyroid disease and 10 healthy control subjects. All subjects underwent a thyroid CDU examination by the same investigator, who was unaware of the laboratory values at the time of the examination. Moreover, all subjects underwent a clinical evaluation, CXCL-10 and thyroid hormonal assessment. RESULTS: CXCL-10 levels were significantly higher in patients with autoimmune diseases and as well as in subjects with an increased thyroid vascularization at CDU. Moreover, CXCL-10 levels were significantly (p<0.05) correlated with inferior thyroid arteria peak systolic velocity (ITA-PSV; r = 0.376) and with thyroid volume even after adjustment for confounding factors. No difference was observed between vascular thyroid pattern at CDU and thyroid circulating hormones while, ITA-PSV was significantly associated with TSH (Adj. r = -0.373; p<0.05). CONCLUSIONS: our data seem to suggest that CXCL-10 could play an important role in the intra-thyroid angiogenesis modulation, explaining, at least partiality, CDU findings typical of thyroid autoimmune diseases. Moreover we confirmed previous reports considering ITA-PSV as the best CDU parameters in the differential diagnosis of thyroid autoimmune disorders.
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Quimiocina CXCL10/sangre , Enfermedad de Graves/sangre , Enfermedad de Hashimoto/sangre , Glándula Tiroides/diagnóstico por imagen , Adulto , Anciano , Biomarcadores/sangre , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/diagnóstico por imagen , Enfermedad de Hashimoto/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica , Glándula Tiroides/irrigación sanguínea , Glándula Tiroides/metabolismo , Tirotropina/sangre , Ultrasonografía Doppler en ColorRESUMEN
OBJECTIVE: The relationship between hypogonadism and erectile dysfunction (ED) has not been completely clarified. Data derived from studies evaluating the effect of testosterone (T) replacement therapy (TRT) on patients with ED have yield mixed results. The purpose of the present study was to evaluate the efficacy and safety of a 50 mg/day of 1% hydroalcoholic testosterone gel applied on non-scrotal skin for hypogonadal men with sexual dysfunction. MATERIAL AND METHODS: We studied a consecutive series of 85 hypogonadal (total testosterone < 12 nmol/L) men (mean age 51.0 +/- 14.0 years) attending our Andrological Unit. Patients were interviewed using ANDROTEST structured interview, a 12-item tool previously validated for the screening of hypogonadism in patients with sexual dysfunction. Patients were also invited to complete erectile function domain of International Index of Erectile Function (IIEF-6;11). Different clinical and biochemical parameters were evaluated at baseline and after 6 months of TRT. RESULTS: Subjects with ED at baseline (61.2%) showed significant increase of IIEF-6 score after 6 months of TRT (9.7 +/- 7.7 vs. 14.6 +/- 9.8, p < 0.001). Furthermore, subjects with more severe hypogonadism at baseline (T in the lowest quartile) showed the best increase in IIEF-6 score. All haematological and biochemical parameters tested remained in the normal rage at the end of the study. CONCLUSIONS: Our study demonstrated that 1% hydroalcoholic testosterone gel is an effective and safe treatment option in subjects with ED.
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Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Hipogonadismo/complicaciones , Testosterona/administración & dosificación , Geles , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Anxiety has a relevant impact on everyday life, including sexual life, and therefore is considered the final common pathway by which social, psychological, and biological stressors negatively affect sexual functioning. The aim of this study is to define the psycho-biological correlates of free-floating anxiety in a large sample of patients complaining of erectile dysfunction (ED)-based sexual problems. We studied a consecutive series of 882 ED patients using SIEDY, a 13-item structured interview, composed of 3 scales that identify and quantify organic, relational, and intrapsychic domains. MHQ-A scoring from Middlesex Hospital Questionnaire (MHQ) was used as a putative marker of free-floating anxiety symptoms (AS). Metabolic and hormonal parameters, nocturnal penile tumescence (NPT) test, and penile Doppler ultrasound (PDU) examination were also performed. MHQ-A score was significantly higher in patients complaining of difficulties in maintaining erection and in those reporting premature ejaculation (6.5 +/- 3.3 vs 5.8 +/- 3.3 and 6.6 +/- 3.3 vs 6.1 +/- 3.3, respectively; both P < .05). Moreover, ASs were significantly correlated to life stressors quantified by SIEDY scale 2 (relational component) and scale 3 (intrapsychic component) scores, as dissatisfaction at work or within the family or couple relationships. Among physical, biochemical, or instrumental parameters tested, only end-diastolic velocity at PDU was significantly (P < .05) related to ASs. In conclusion, in patients with ED-based sexual problems, ASs are correlated to many relational and life stressors. Conversely, organic problems are not necessarily associated with MHQ-A score.