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Due to increasing consumption and urbanisation, urban waste management and recycling are a primary concern in Italy. Italian waste collection underwent significant reform with the introduction of a sorted collection target of 65% of total collected waste in Legislative Decree No. 152/2006. In this article, we analyse the effect of this regulatory target on the efficiency of waste collection in 275 Italian municipalities in the years 2016-2019. We estimate the coefficients of the cost efficiencies of the sorted and unsorted waste without assuming functional forms for the efficient frontier or the distribution of efficiency. Our findings suggest that municipalities that met the 65% sorted waste target demonstrated higher efficiency as costs increased, whereas those that failed to meet the target demonstrated higher inefficiency as costs increased. Strong effects emerged for population and urban economic development on the success of waste collection, whereas only marginal effects were observed for population density and city size. To improve the situation of municipalities that are not meeting the 65% target, we propose several policy measures, including 'neighbourhood solidarity'.
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Understanding of the pairing statistics in solutions populated by a large number of distinct solute species with mutual interactions is a challenging topic, relevant in modeling the complexity of real biological systems. Here we describe, both experimentally and theoretically, the formation of duplexes in a solution of random-sequence DNA (rsDNA) oligomers of length L = 8, 12, 20 nucleotides. rsDNA solutions are formed by 4L distinct molecular species, leading to a variety of pairing motifs that depend on sequence complementarity and range from strongly bound, fully paired defectless helices to weakly interacting mismatched duplexes. Experiments and theory coherently combine revealing a hybridization statistics characterized by a prevalence of partially defected duplexes, with a distribution of type and number of pairing errors that depends on temperature. We find that despite the enormous multitude of inter-strand interactions, defectless duplexes are formed, involving a fraction up to 15% of the rsDNA chains at the lowest temperatures. Experiments and theory are limited here to equilibrium conditions.
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ADN , Conformación de Ácido Nucleico , Hibridación de Ácido Nucleico , Soluciones , Temperatura , TermodinámicaRESUMEN
OBJECTIVE: Obesity has become an epidemic in the United States. Although bariatric surgery can effectively achieve weight loss by altering the gastrointestinal tract, it commonly results in micronutrient deficiency, requiring supplementation. Iodine is an essential micronutrient for the synthesis of thyroid hormones. We aimed to investigate changes in urinary iodine concentrations (UIC) in patients following bariatric surgery. METHODS: 85 adults who underwent either laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass surgery were enrolled. At baseline and 3 months after surgery, we evaluated spot UIC and serum thyroid stimulating hormone (TSH), vitamin D, vitamin B12, ferritin, and folate levels. Participants provided a 24-hour diet recall for iodine-rich foods and information about multivitamin use at each time point. RESULTS: There was a significant increase in median UIC (201 [120.0 - 288.5] vs 334.5 [236.3 - 740.3] µg/L; P < .001), a significant decrease in mean body mass index (44.0 ± 6.2 vs 35.8 ± 5.9; P < .001) and a significant decrease in TSH levels (1.5 [1.2 - 2.0] vs 1.1 [0.7 - 1.6] uIU/mL; P < .001) at 3 months postoperatively compared to baseline. Body mass index, UIC, and TSH levels before and after surgery did not differ based on the type of weight loss surgery. CONCLUSION: In an iodine-sufficient area, bariatric surgery does not cause iodine deficiency nor clinically significant changes in thyroid function. Different surgical procedures with different anatomical alterations in the gastrointestinal tract do not significantly affect iodine status.
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Cirugía Bariátrica , Derivación Gástrica , Yodo , Obesidad Mórbida , Adulto , Humanos , Obesidad Mórbida/cirugía , Obesidad Mórbida/epidemiología , Yodo/orina , Tirotropina , VitaminasRESUMEN
This paper was originally published under standard Nature America Inc. copyright. As of the date of this correction, the Resource is available online as an open-access paper with a CC-BY license. No other part of the paper has been changed.
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BACKGROUND: Controversies remain about the ideal risk-based surgical approach for differentiated thyroid cancer (DTC). METHODS: At a single tertiary care institution, 370 consecutive patients with low- or intermediate-risk DTC were submitted to either lobectomy (LT) or total thyroidectomy (TT) and were followed up. RESULTS: Event-free survival by Kaplan-Meier curves was significantly higher after TT than after LT for the patients with either low-risk (P = 0.004) or intermediate-risk (P = 0.032) tumors. At the last follow-up visit, the prevalence of event-free patients was higher in the TT group than in the LT low-risk group (95% and 87.5%, respectively; P = 0.067) or intermediate-risk group (89% and 50%; P = 0.008). No differences in persistence prevalence were found among microcarcinomas treated by LT or TT (low risk, P = 0.938 vs. intermediate-risk, P = 0.553). Nevertheless, 15% of the low-risk and 50% of the intermediate-risk microcarcinomas treated by LT were submitted to additional treatments. On the other hand, macrocarcinomas were significantly more persistent if treated with LT than with TT (low-risk, P = 0.036 vs. intermediate-risk, P = 0.004). Permanent hypoparathyroidism was more frequent after TT (P = 0.01). After LT, thyroglobulin (Tg)/thyroid-stimulating hormone (TSH) had shown decreasing trend in 68% of the event-free patients and an increasing trend in the persistent cases. CONCLUSIONS: Lobectomy can be proposed for low-risk microcarcinomas, although in a minority of cases, additional treatments are needed, and a longer follow-up period usually is required to confirm an event-free outcome compared with that for patients treated with TT. On the other hand, to achieve an excellent response, TT should be favored for intermediate-risk micro- and macro-DTCs despite the higher frequency of postsurgical complications.
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Neoplasias de la Tiroides , Tiroidectomía , Humanos , Estudios Retrospectivos , Factores de Riesgo , Tiroglobulina , Neoplasias de la Tiroides/cirugía , TirotropinaRESUMEN
Access to primary research data is vital for the advancement of science. To extend the data types supported by community repositories, we built a prototype Image Data Resource (IDR) that collects and integrates imaging data acquired across many different imaging modalities. IDR links data from several imaging modalities, including high-content screening, super-resolution and time-lapse microscopy, digital pathology, public genetic or chemical databases, and cell and tissue phenotypes expressed using controlled ontologies. Using this integration, IDR facilitates the analysis of gene networks and reveals functional interactions that are inaccessible to individual studies. To enable re-analysis, we also established a computational resource based on Jupyter notebooks that allows remote access to the entire IDR. IDR is also an open source platform that others can use to publish their own image data. Thus IDR provides both a novel on-line resource and a software infrastructure that promotes and extends publication and re-analysis of scientific image data.
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Sistemas de Administración de Bases de Datos , Bases de Datos Factuales , Interpretación de Imagen Asistida por Computador/métodos , Difusión de la Información/métodos , Programas Informáticos , Interfaz Usuario-Computador , Algoritmos , Edición , Integración de SistemasRESUMEN
Monoacylglycerol lipase (MAGL) is a serine hydrolase that has a key regulatory role in controlling the levels of 2-arachidonoylglycerol (2-AG), the main signaling molecule in the endocannabinoid system. Identification of selective modulators of MAGL enables both to provide new tools for investigating pathophysiological roles of 2-AG, and to discover new lead compounds for drug design. The development of sensitive and reliable methods is crucial to evaluate this modulatory activity. In the current study, we report readily synthesized long-wavelength putative fluorogenic substrates with different acylic side chains to find a new probe for MAGL activity. 7-Hydroxyresorufinyl octanoate proved to be the best substrate thanks to the highest rate of hydrolysis and the best Km and Vmax values. In addition, in silico evaluation of substrates interaction with the active site of MAGL confirms octanoate resorufine derivative as the molecule of choice. The well-known MAGL inhibitors URB602 and methyl arachidonylfluorophosphonate (MAFP) were used for the assay validation. The assay was highly reproducible with an overall average Z' value of 0.86. The fast, sensitive and accurate method described in this study is suitable for low-cost high-throughput screening (HTS) of MAGL modulators and is a powerful new tool for studying MAGL activity.
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Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Colorantes Fluorescentes , Ensayos Analíticos de Alto Rendimiento , Monoacilglicerol Lipasas/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Hidrólisis , Cinética , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Monoacilglicerol Lipasas/química , Reproducibilidad de los Resultados , Relación Estructura-ActividadRESUMEN
Unfortunately, the fourth author's middle name was missed out in the original publication of this article. The complete correct name should read as follows.
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Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. ß blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment.
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Antitiroideos/uso terapéutico , Hipertiroidismo , Radioisótopos de Yodo/uso terapéutico , Complicaciones del Embarazo , Glándula Tiroides/metabolismo , Hormonas Tiroideas/sangre , Tiroidectomía , Antagonistas Adrenérgicos beta/uso terapéutico , Amiodarona/administración & dosificación , Amiodarona/efectos adversos , Antitiroideos/administración & dosificación , Antitiroideos/efectos adversos , Diagnóstico Diferencial , Esquema de Medicación , Femenino , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/metabolismo , Enfermedad de Graves/terapia , Humanos , Hipertiroidismo/diagnóstico , Hipertiroidismo/epidemiología , Hipertiroidismo/metabolismo , Hipertiroidismo/terapia , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/efectos adversos , Grupo de Atención al Paciente , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/metabolismo , Complicaciones del Embarazo/terapia , Factores de Riesgo , Crisis Tiroidea/diagnóstico , Crisis Tiroidea/terapia , Hormonas Tiroideas/biosíntesis , Tiroidectomía/efectos adversos , Tirotoxicosis/diagnóstico , Tirotoxicosis/tratamiento farmacológico , Tirotoxicosis/metabolismoRESUMEN
Fetal cell microchimerism (FCM) is defined as the persistence of fetal cells in maternal organs and circulation without any apparent rejection and it was hypothesized to protect toward the onset of some neoplastic diseases. To verify the role of FCM in papillary thyroid cancer (PTC), we enrolled 87 parous women with PTC and at least one male pregnancy preceding the diagnosis (PTC-P), 66 healthy women with 1 or more male children (HC-P) and 57 nonparous women with PTC (PTC-NP). The presence of circulating male DNA was assessed by the amplification of the Y chromosome-specific gene SRY, with a sensitivity of 1 male cell/1 million female cells. A significantly higher frequency of FCM was found in HC-P than PTC-P women (63.6% vs. 39.1%, p = 0.004). Among PTC-P patients, those positive for the presence of FCM (FMC+ve) had a lower prevalence of extrathyroidal extension (p = 0.027) and lymph node metastases (p = 0.044) than those without FCM (FMC-ve). Moreover, FMC+ve patients were more frequently in remission than FMC-ve cases (94.1 vs. 67.9%, p = 0.009). Interestingly, we showed for the first time that the positive effect on tumor presentation and outcome is specifically related to FCM and it is not an effect of pregnancy. In conclusion, circulating FCM is significantly more frequent in healthy parous women than in women with PTC. Moreover, the presence of circulating fetal male cells is associated with a significantly lower extrathyroidal extension and a good prognosis, suggesting a protective role of this phenomenon toward both the onset and the progression of thyroid cancer.
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Carcinoma Papilar/patología , Quimerismo , Neoplasias de la Tiroides/patología , Adulto , Carcinoma Papilar/terapia , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paridad , Neoplasias de la Tiroides/terapia , Resultado del TratamientoRESUMEN
Data-intensive research depends on tools that manage multidimensional, heterogeneous datasets. We built OME Remote Objects (OMERO), a software platform that enables access to and use of a wide range of biological data. OMERO uses a server-based middleware application to provide a unified interface for images, matrices and tables. OMERO's design and flexibility have enabled its use for light-microscopy, high-content-screening, electron-microscopy and even non-image-genotype data. OMERO is open-source software, available at http://openmicroscopy.org/.
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Sistemas de Administración de Bases de Datos , Bases de Datos Factuales , Interpretación de Imagen Asistida por Computador/métodos , Almacenamiento y Recuperación de la Información/métodos , Modelos Biológicos , Programas Informáticos , Interfaz Usuario-Computador , Animales , Biología/métodos , Simulación por Computador , HumanosRESUMEN
SUMMARY: BioBlend.objects is a new component of the BioBlend package, adding an object-oriented interface for the Galaxy REST-based application programming interface. It improves support for metacomputing on Galaxy entities by providing higher-level functionality and allowing users to more easily create programs to explore, query and create Galaxy datasets and workflows. AVAILABILITY AND IMPLEMENTATION: BioBlend.objects is available online at https://github.com/afgane/bioblend. The new object-oriented API is implemented by the galaxy/objects subpackage.
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Biología Computacional/métodos , Algoritmos , Automatización , Gráficos por Computador , Sistemas de Computación , Lenguajes de Programación , Programas Informáticos , Interfaz Usuario-ComputadorRESUMEN
The targeting of BCR-ABL, a hybrid oncogenic tyrosine (Y) kinase, does not eradicate chronic myeloid leukemia (CML)-initiating cells. Activation of ß-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL-dependent Y phosphorylation and impaired binding to GSK3ß (glycogen synthase kinase 3ß). Herein, we show that GSK3ß is constitutively Y(216) phospho-activated and predominantly relocated to the cytoplasm in primary CML stem/progenitor cells compared with its balanced active/inactive levels and cytosolic/nuclear distribution in normal cells. Under cytokine support, persistent GSK3ß activity and its altered subcellular localization were correlated with BCR-ABL-dependent and -independent activation of MAPK and p60-SRC/GSK3ß complex formation. Specifically, GSK3ß activity and nuclear import were increased by imatinib mesylate (IM), a selective ABL inhibitor, but prevented by dasatinib that targets both BCR-ABL- and cytokine-dependent MAPK/p60-SRC activity. SB216763, a specific GSK3 inhibitor, promoted an almost complete suppression of primary CML stem/progenitor cells when combined with IM, but not dasatinib, while sparing bcr-abl-negative cells. Our data indicate that GSK3 inhibition acts to prime a pro-differentiative/apoptotic transcription program in the nucleus of IM-treated CML cells by affecting the ß-catenin, cyclinD1, C-EBPα, ATF5, mTOR, and p27 levels. In conclusion, our data gain new insight in CML biology, indicating that GSK3 inhibitors may be of therapeutic value in selectively targeting leukemia-initiating cells in combination with IM but not dasatinib.
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Apoptosis/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Piperazinas/farmacología , Pirimidinas/farmacología , Antígenos CD34/metabolismo , Benzamidas , Western Blotting , Núcleo Celular/metabolismo , Células Cultivadas , Ciclina D1/metabolismo , Citocinas/farmacología , Dasatinib , Sinergismo Farmacológico , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Células Madre Hematopoyéticas/metabolismo , Humanos , Mesilato de Imatinib , Indoles/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Maleimidas/farmacología , Microscopía Confocal , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Transducción de Señal/efectos de los fármacos , Tiazoles/farmacología , beta Catenina/metabolismoRESUMEN
PURPOSE: The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. METHODS: We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. RESULTS: Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). CONCLUSION: The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.
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Carcinoma Papilar/radioterapia , Quimioradioterapia Adyuvante , Radioisótopos de Yodo/uso terapéutico , Radiofármacos/uso terapéutico , Glándula Tiroides/efectos de la radiación , Neoplasias de la Tiroides/radioterapia , Tirotropina/uso terapéutico , Adenocarcinoma Folicular/tratamiento farmacológico , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirugía , Adulto , Carcinoma/tratamiento farmacológico , Carcinoma/patología , Carcinoma/radioterapia , Carcinoma/cirugía , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Carcinoma Papilar Folicular/tratamiento farmacológico , Carcinoma Papilar Folicular/patología , Carcinoma Papilar Folicular/radioterapia , Carcinoma Papilar Folicular/cirugía , Terapia Combinada , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Neoplasia Residual/epidemiología , Neoplasia Residual/prevención & control , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Riesgo , Cáncer Papilar Tiroideo , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Tirotropina/genética , Imagen de Cuerpo EnteroRESUMEN
Waste management is crucial for advancing the circular economy, and Italy has begun to address this issue by organizing municipalities into collaborative communities of municipalities, named ATOs. In this paper, we propose a quantitative approach based on conditional efficiency analysis to estimate viable eco-efficiency targets for these waste collection communities. The proposed targets are both eco-efficient, because they reflect optimal resource allocation within the eco-efficiency framework, and viable, because they consider the unique specificities of each waste community. The methodology determines a pathway or direction for municipalities to reach the eco-efficiency frontier based on specific external factors, ensuring that each municipality is benchmarked against others with similar contexts within the same community. Our analysis focuses on 89 Italian municipalities within the ATO "Città metropolitana di Roma Capitale" in 2021, revealing that size and economic development significantly contributed to viable eco-efficiency within the community during this period. The proposed approach is general and flexible and can be applied to other municipalities in Italy or across Europe. It can also be extended to meso (regional) or macro (country) levels of analysis.
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INTRODUCTION: Vitamin D is an essential hormone for humans, playing an important role in musculoskeletal and calcium homeostasis. Its deficiency/insufficiency seems to contribute to the development of cardiometabolic diseases in adults: this correlation appears less clear for children and adolescents. The aim of this paper was to review literature data on the relationship between vitamin D and lipid profile alterations in pediatric population. EVIDENCE ACQUISITION: We carried out a comprehensive research in electronic databases, including MEDLINE and PubMed up to December 2022, for cross-sectional or prospective studies that investigated the correlation between serum vitamin D levels and lipid profile in children and adolescents. At the end of the process, 37 articles were included in this review. EVIDENCE SYNTHESIS: According to our findings, vitamin D deficiency/insufficiency is strongly associated with lower high-density lipoprotein (HDL) cholesterol levels and higher levels of triglycerides and total cholesterol. Data about low-density lipoproteins (LDL) cholesterol are inconsistent. The potential role of vitamin D supplements for the prevention of cardiometabolic disease currently remains a speculation. CONCLUSIONS: An increasing number of studies shows how hypovitaminosis D in the pediatric age may play a role in the pathogenesis of metabolic disorders and lipid profile alterations. Data regarding the potential role of vitamin D supplements for the prevention of cardiometabolic disease are currently controversial. Further studies are needed to evaluate the causality of this association and to assess the underlying pathogenetic mechanisms.
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Background: Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption, or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI). Aim: The objective was to assess the entire adrenal function in patients on systemic treatments. Methods: ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, six on vandetanib, and five on selpercatinib). ACTH stimulation tests were performed in 26 cases. Results: After a median treatment period of 7 months, we observed an increase in ACTH values in 80-100% of patients and an impaired cortisol response to the ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-androstenedione and 17-OH progesterone levels were below the median of normal values in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of normal values in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the normal values in most cases, whilst renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI. Conclusion: Our data confirm that systemic treatments for advanced thyroid cancer can lead to impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been first reported and should be considered in the more appropriate management of these fragile patients.
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Corteza Suprarrenal , Piperidinas , Neoplasias de la Tiroides , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Insuficiencia Suprarrenal/tratamiento farmacológico , Hormona Adrenocorticotrópica/sangre , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Fatiga/etiología , Hidrocortisona , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Quinazolinas/uso terapéutico , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patologíaRESUMEN
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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Open and practical exchange, dissemination, and reuse of specimens and data have become a fundamental requirement for life sciences research. The quality of the data obtained and thus the findings and knowledge derived is thus significantly influenced by the quality of the samples, the experimental methods, and the data analysis. Therefore, a comprehensive and precise documentation of the pre-analytical conditions, the analytical procedures, and the data processing are essential to be able to assess the validity of the research results. With the increasing importance of the exchange, reuse, and sharing of data and samples, procedures are required that enable cross-organizational documentation, traceability, and non-repudiation. At present, this information on the provenance of samples and data is mostly either sparse, incomplete, or incoherent. Since there is no uniform framework, this information is usually only provided within the organization and not interoperably. At the same time, the collection and sharing of biological and environmental specimens increasingly require definition and documentation of benefit sharing and compliance to regulatory requirements rather than consideration of pure scientific needs. In this publication, we present an ongoing standardization effort to provide trustworthy machine-actionable documentation of the data lineage and specimens. We would like to invite experts from the biotechnology and biomedical fields to further contribute to the standard.