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1.
Sci Rep ; 14(1): 15038, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951621

RESUMO

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.

2.
Eur Thyroid J ; 13(3)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38642580

RESUMO

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.


Assuntos
Córtex Suprarrenal , Piperidinas , Neoplasias da Glândula Tireoide , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Insuficiência Adrenal/tratamento farmacológico , Hormônio Adrenocorticotrópico/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Fadiga/etiologia , Hidrocortisona , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38224323

RESUMO

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.

4.
Learn Health Syst ; 8(1): e10365, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38249839

RESUMO

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.

5.
Thyroid ; 33(11): 1318-1326, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37725571

RESUMO

Background: There is some controversy on the potential relationship between autoimmune processes and clinicopathologic features as well as prognosis of differentiated thyroid cancer (DTC), and the evidence is limited by its largely retrospective nature. We examined the relationship between the presence of autoimmune thyroiditis (AT) and 1-year thyroid cancer treatment outcomes in a large multicenter study using prospectively collected data. Methods: We included data from consecutive DTC patients enrolled in the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339). We divided the groups according to the presence (AT) or absence (no autoimmune thyroiditis [noAT]) of associated AT. We used propensity score matching to compare the clinical features and outcomes between the two groups at 1-year follow-up. Results: We included data from 4233 DTC patients, including 3172 (75%) females. The American Thyroid Association (ATA) risk levels were as follows: 51% (2160/4233) low risk, 41.3% (1750/4233) intermediate risk, and 7.6% (323/4233) high risk. There were 1552 patients (36.7%) who had AT. Before propensity score matching, AT patients were significantly younger and had a smaller and bilateral tumor (p < 0.0001). Patients with AT more frequently fell into the low- and intermediate-risk categories, while the ATA high risk was more frequent among noAT patients (p = 0.004). After propensity score matching, patients with AT more frequently showed evidence of disease (structural/biochemical incomplete response) versus excellent/indeterminate response, compared with patients without AT (7.3% vs. 4.5%, p = 0.001), with an odds ratio of 1.86 ([confidence interval: 1.3-2.6], p = 0.0001). However, when considering only structural persistence as the outcome, no statistically significant differences were observed between patients with or without AT (3.4% vs. 2.7%, p = 0.35). The elevated risk associated with the ATA intermediate and high risk at diagnosis remained consistently statistically significant. Conclusions: In this large prospective series, biochemical persistence was more frequent, at 1-year follow-up, in AT patients. However, there was no significant association between the presence of AT and structural persistence of disease. These findings may be explained by the presence of a residual thyroid tissue.


Assuntos
Adenocarcinoma , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Tireoidite Autoimune , Feminino , Humanos , Masculino , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Tireoidite Autoimune/complicações , Resultado do Tratamento , Estudos Prospectivos
8.
Endocr Pract ; 29(9): 710-715, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37385530

RESUMO

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.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Iodo , Obesidade Mórbida , Adulto , Humanos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/epidemiologia , Iodo/urina , Tireotropina , Vitaminas
9.
Data Brief ; 48: 109163, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37168599

RESUMO

We provide data describing all the largest Italian Universities from several perspectives, including scientific research, administrative and economic point of view. In particular, associated with each University, we have the following data. (a) The list of the most representative research keywords (single words and bigrams), automatically extracted from titles, abstracts and other possible metadata of all the research publications available for that University in Scopus database at October 2022. (b) The Extended_name of the University, Status, University_Type, State_status, number of Managerial and Administrative Staff, Teaching Staff and Researchers, Phd Diplomas, Phd Enrollments, Enrolled Undergraduates, Enrolled Graduates, Graduates, Master I Lv Graduates, Enrolled Master's Degree I Lv, Master II Lv, Graduates Enrolled, Master II Lv, Graduates Specialistic Schools and Enrolled Specialistic Schools were extracted from USTAT database for the years 2016-2018. (c) The data of Educational Income, Income from Commissioned Research and Technology Transfer, Income from Research with competitive funding, Own Income, Contributions from others (private), Contributions from others (public), Contributions from universities, Contributions from the European Union and the Rest of the World, Contributions from other local governments, Contributions Regions and Autonomous Provinces, MIUR and other central government grants, Operating Costs, Current Management Costs, Managerial and administrative personnel costs, Research and teaching staff cost, Cost of Lecturers and Researchers, Cost Scientific Collaborators, Cost of Contract Teachers, Cost of Language Experts, Other research and teaching personnel costs, Personnel Costs, Scientific equipment, Concessions, licenses and trademarks, Patent rights are extracted from the unique University Balance Sheet of each university for the years 2016-2018. These data were of difficult availability; they have been extracted from several heterogeneous sources and have been automatically checked, cleaned from errors, integrated, and missing values have been imputed as much as possible. However, due to large missing portions in the sources, they still contain several missing parts. Nonetheless, they represent a powerful snapshot of the Italian Universities, and can be of interest to researchers for many analyses of the Italian academic world. All the sources of the openly available data are provided.

10.
Eur Thyroid J ; 12(4)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37097040

RESUMO

Background: Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited. Aim: The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort. Methods: Twenty-nine patients were followed up for a mean time of 29.8 months (6-77 months). Results: After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CCBs were associated with one or more anti-hypertensive drug. Conclusion: HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.


Assuntos
Antineoplásicos , Hipertensão , Compostos de Fenilureia , Quinolinas , Neoplasias da Glândula Tireoide , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Incidência , Proteinúria/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Humanos , Seguimentos , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
11.
Ann Endocrinol (Paris) ; 84(3): 374-381, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36963756

RESUMO

Tyrosine kinase inhibitors (TKIs) have improved outcome for many tumors. Although better tolerated than cytotoxic chemotherapy, they may cause several adverse events (AEs) and various endocrine-related toxicities have been reported under TKI treatment. The toxicity profile varies between the different TKI compounds. This review focuses on the main endocrinopathies caused by TKIs. Thyroid dysfunction and, in particular, hypothyroidism are the most frequent and best described. Several potential mechanisms have been hypothesized, including thyroid gland dysfunction, hormone metabolism impairment and hypothalamus-pituitary-thyroid axis imbalance. TKIs have been reported to influence almost all glands. In particular, they are associated with adrenal insufficiency, growth retardation due to growth hormone (GH) and/or insulin-like growth factor-1 (IGF1) deficiency, hypogonadism, and male and female fertility impairment. TKIs may affect bone metabolism, in particular decreasing osteoclastogenesis and bone turnover and, in turn, they may cause secondary hyperparathyroidism. Hypocalcemia has been reported under lenvatinib and vandetanib treatment and parathyroid hormone (PTH)-dependent and PTH-independent mechanisms have been hypothesized. Metabolic alterations during TKI treatment range from hypoglycemia with imatinib and dasatinib to hyperglycemia with nilotinib; dyslipidemia improved with imatinib and worsened with nilotinib, sunitinib, pazopanib, sorafenib, and famitinib. Endocrine-related AEs should be managed by dedicated endocrinologists. Hormone deficiencies are easily managed by replacement therapy, while endocrine hyperfunction may be improved by symptomatic treatment. Severe situations should be managed in coordination with the oncologist, trying to limit the need for TKI dose reduction or interruption.


Assuntos
Antineoplásicos , Doenças da Glândula Tireoide , Masculino , Humanos , Feminino , Mesilato de Imatinib/efeitos adversos , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Doenças da Glândula Tireoide/induzido quimicamente , Hormônios
12.
Thyroid ; 33(1): 74-81, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326203

RESUMO

Background: Several toxicities are recorded during treatment of advanced thyroid cancer (TC) with antiangiogenic drugs, including lenvatinib (LEN). Hypocalcemia was reported in registration studies, but little data are available from real-life cohorts. The aim of our study was to describe the incidence, characteristics, and the management of hypocalcemia in patients on LEN treatment. Methods: This is a retrospective cohort study of consecutive patients with advanced TC, treated with LEN for at least six months at a single tertiary center in Italy. Phosphocalcic metabolism was evaluated during treatment. Results: We included 25 patients treated for a mean of 29 ± 19 months (range 6-68 months). Hypocalcemia occurred in 6 of the 25 patients (24% [95% confidence interval 9.36-45.13%]), being of grade ≥3 in 2 of the 25 patients (8%), and recurrent in 4 of 6 patients (67%). The median time to hypocalcemia onset was 3 months (range 0.5-13 months) from starting LEN. No differences were found between patients who developed or not hypocalcemia regarding either starting/mean dose of LEN or clinicopathological characteristics. During the hypocalcemic crisis, the 2 patients with grade ≥3 hypocalcemia had low magnesium and low or inappropriately normal parathormone (PTH) levels, while 2 of 3 patients with grade 2 hypocalcemia had a secondary hyperparathyroidism. Hypocalcemia was managed with calcium oral supplementation in most cases, although up to 10% of patients required intravenous calcium treatment and transient LEN withdrawal. Conclusions: In this relatively small cohort, we observed an incidence of hypocalcemia of 24%, which is higher than that reported in the registration trial (6.9%). Both PTH-dependent and PTH-independent mechanisms explained hypocalcemia in the present cohort. Monitoring of serum calcium levels is strongly advised during the first year of LEN treatment, as hypocalcemia may be severe. More research is needed to confirm our findings and inform possible risk factors for hypocalcemia in advanced TC patients treated with LEN.


Assuntos
Hipocalcemia , Neoplasias da Glândula Tireoide , Humanos , Cálcio , Hipocalcemia/induzido quimicamente , Hormônio Paratireóideo , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos
13.
Cancers (Basel) ; 14(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36428608

RESUMO

Scanty data are available on the progression risk in patients with persistent thyroid cancer (TC) before pregnancy. We aimed to evaluate this topic in our series and to review available literature data. This was a retrospective study performed in a tertiary care Italian TC center. We included 8 patients with persistent papillary TC who became pregnant after initial treatments (mean time interval of 62 months). Seven patients had the structural disease (lung and/or neck node metastases), while one patient had biochemical persistence. During a mean follow-up of 97 months, none of the patients showed disease progression either during pregnancy or during a follow-up of at least 12 months after delivery, and no additional treatments were needed. A sequential biochemical evaluation showed that thyroglobulin levels can significantly increase during pregnancy, returning to preconception levels after delivery. In conclusion, our data confirm that pregnancy is not associated with disease progression in patients with stable local and/or distant persistence before conception. Thus, pregnancy should not be contraindicated in metastatic women, although a precise clinical characterization, including the disease stage at diagnosis, the ATA risk class, and the dynamic risk stratification, should be conducted before conception.

14.
Prev Vet Med ; 208: 105732, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35988391

RESUMO

Paratuberculosis is a chronic enteric progressive disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP). Despite cultural methods being considered the gold standard for the diagnosis of paratuberculosis, quantitative PCR (qPCR) assays have been developed for this purpose. These assays showed sensitivity and specificity comparable to cultural method but provide more rapid analysis results. Aim of our work was the validation of an IS900-qPCR assay for detection of MAP in faeces according to the OIE guidelines relative to the validation of assays for infectious diseases. The analytical and diagnostic characteristics and the reproducibility of the qPCR method were assessed. The robustness of the assay was evaluated using two extraction methods (silica column and magnetic beads DNA capture) and two qPCR systems (STEPONE™ and CFX96™). According to our validation, the analytical specificity, inclusivity and exclusivity were found to be appropriate for the use of this qPCR assay as a diagnostic test. Specifically, the limit of detection was approximately 100 CFU/g or even less if binomial approaches were used for the determination of the 95 % probability of detection (logit and clog-log models) with sufficient repeatability and reproducibility. Estimation of test accuracy was performed using a Bayesian two latent class model, in various scenarios combining different priors for prevalence and accuracy of the two tests used. All models were run considering three different cut-offs for qPCR. Our validation study underlines the good performance of this IS900-qPCR assay for diagnosis of MAP representing a valid and robust alternative to culture. Moreover, coupled with the semiautomatic magnetic beads DNA extraction method, this assay allows the rapid processing of numerous samples.


Assuntos
Doenças dos Bovinos , Mycobacterium avium subsp. paratuberculosis , Paratuberculose , Animais , Bovinos , Mycobacterium avium subsp. paratuberculosis/genética , Paratuberculose/diagnóstico , Paratuberculose/microbiologia , Reprodutibilidade dos Testes , Teorema de Bayes , DNA Bacteriano/genética , Fezes/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Sensibilidade e Especificidade , Dióxido de Silício , Doenças dos Bovinos/microbiologia
15.
Front Endocrinol (Lausanne) ; 13: 875875, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898450

RESUMO

Optimized preoperative diagnostic tools with calcitonin tests, ultrasound features, functional imaging modalities, and genetic testing to detect hereditary forms have led to an increased rate of earlier diagnosis and surgery for medullary thyroid cancer (MTC). This helps to adapt the primary surgery to the tumor stage and avoid surgical overtreatment for localized tumor growth, i.e., deviating from the regularly recommended thyroidectomy with bilateral central lymph node dissection in favor of a limited unilateral approach. To limit primary surgical therapy, it is crucial that the MTC is clinically unifocal, sporadic, and confined to the thyroid, and that calcitonin levels indicate biochemical recovery after surgery. The main requirement for such a limited approach is the availability of frozen section studies that reliably indicate (i) R0 resection of the MTC, (ii) absence of infiltration of the organ capsule, (iii) lack of desmoplasia (i.e., evidence of the metastatic potential of the MTC), (iiii) absence of contralateral disease or precancerous lesions. Informed consent is mandatory from the patient, who has been fully informed of the advantages, disadvantages, and potential risks of not undergoing the "classic" surgical procedure. The aim of this article is to review the guidelines for the management of early-stage MTC.


Assuntos
Carcinoma Medular , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Calcitonina , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Carcinoma Neuroendócrino/cirurgia , Humanos , Guias de Prática Clínica como Assunto , Neoplasias da Glândula Tireoide/patologia
16.
Front Oncol ; 12: 903532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860593

RESUMO

In a minority of differentiated thyroid cancer (TC) cases and in a large percentage of poorly differentiated TCs (PDTCs) and anaplastic TCs (ATCs), the prognosis is poor due to the lack of response to conventional treatments. In the last two decades, multikinase inhibitor (MKI) compounds have been developed and demonstrated to be very effective in these aggressive cases. Besides the great efficacy, several adverse events (AEs) have been reported in virtually all patients treated with MKIs, largely overlapping between different compounds and including hypertension, diarrhea, anorexia, decreased weight, fatigue, and proteinuria. Most grade 3-4 adverse reactions occur during the first 6 months of treatment and require dosage reduction and/or drug discontinuation. Due to severity of the AEs related to the treatment with MKIs, a multidisciplinary team is definitely required for the daily management of these patients, for the evaluation of the disease status, and the psychophysical condition. Moreover, it is crucial that the patients could have a facilitated access to reach either specialist doctors or nurses who must have been trained to follow them for their individual clinical complications. The follow-up visits should take place at monthly intervals until the sixth month and then every 1-2 months until the completion of the first year of treatment. The flow chart followed at our tertiary center is reported in the present review as a real-life-based example for the follow-up of patients with advanced TC on MKI treatment.

17.
Endocrine ; 78(1): 197-200, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35857272

RESUMO

CONTEXT: Radioiodine refractory differentiated thyroid cancer can be effectively treated with multi-tyrosine-kinase inhibitors (MKIs). Hypocalcaemia has been reported among the side effects of these drugs, but little is known about its pathophysiology and clinical relevance. CASE REPORT: We report the case of a 78-years-old woman with an aggressive papillary thyroid cancer infiltrating perithyroidal structures. The extent of surgery was limited to hemithyroidectomy, RAI treatment could not be performed, and she started lenvatinib treatment. After 4 months of therapy, the patient accessed the Emergency Department for a grade III hypocalcaemia (corrected serum calcium: 6.6 mg/dL, n.v. 8.1-10.4 mg/dL), due to primary hypoparathyroidism (serum PTH: 12.6 ng/L, n.v. 13-64 ng/L). The patient was treated with intravenous calcium infusions and vitamin D supplementation. After discharge, the oral dose of carbonate calcium (CaCO3) was of 6 g/day, and was titrated according to blood exams. Two weeks after discharge, while taking CaCO3 at the dose of 3 g/day, the patient experienced symptomatic grade II hypercalcemia (corrected serum calcium: 11.6 mg/dL), associated to the spontaneous reprise of PTH secretion, and leading to oral calcium withdrawal. During the subsequent follow-up, the patient remained eucalcemic without calcium supplementation. CONCLUSIONS: Though hypocalcaemia has been described as potential side effect of MKI treatment, this is the first report of a lenvatinib-induced primary hypoparathyroidism, in a patient with a documented normal parathyroid function after surgery. The periodical assessment of calcium-phosphorus metabolism is thus warranted to prevent this potentially lethal side effect, in both post-surgical hypoparathyroid and euparathyroid patients.


Assuntos
Hipocalcemia , Hipoparatireoidismo , Neoplasias da Glândula Tireoide , Idoso , Cálcio , Feminino , Humanos , Hipoparatireoidismo/induzido quimicamente , Hipoparatireoidismo/tratamento farmacológico , Radioisótopos do Iodo/uso terapêutico , Hormônio Paratireóideo , Compostos de Fenilureia , Quinolinas , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos
18.
PLoS Comput Biol ; 18(4): e1010051, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35404933

RESUMO

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.


Assuntos
DNA , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Soluções , Temperatura , Termodinâmica
19.
Updates Surg ; 74(1): 309-316, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34564834

RESUMO

Transient postoperative hypocalcemia is a common complication after total thyroidectomy. Evidence on contributing metabolic factors is contradictory. Our work aims to define the role of preoperative 25-hydroxyvitaminD levels in developing transient postoperative hypocalcemia. 183 consecutive patients who underwent total thyroidectomy at our institution (May 2017-December 2019) were included in the retrospective study. We reported gender, age, estimated glomerular filtration rate, creatinine, preoperative 25-hydroxyvitaminD, serum pre- and postoperative calcium, pre- and postoperative PTH levels and transient postoperative hypocalcemia occurrences. We compared variables both among patients with and without transient postoperative hypocalcemia and between patients with different 25-hydroxyvitaminD levels (< 10 ng/ml deficitary; 11-30 ng/ml insufficient; > 30 ng/ml, normal). A binomial logistic regression model evaluating the risk for transient postoperative hypocalcemia was elaborated. Patients with transient postoperative hypocalcemia had lower levels of postoperative PTH (p < 0.001) and more frequently normal or deficitary 25-hydroxyvitaminD levels (p = 0.05). When comparing patients according to their 25-hydroxyvitaminD levels, insufficiency was associated with a lower rate of transient postoperative hypocalcemia (p = 0.05); deficiency was associated with higher preoperative PTH (p = 0.021), postoperative PTH (p = 0.043) and estimated glomerular filtration rate (p = 0.031) and lower serum creatinine (p = 0.014). In the regression model higher preoperative PTH (OR = 1.011, p = 0.041) and 25-hydroxyvitaminD deficiency (OR = 0.343, p = 0.011) significantly predicted transient postoperative hypocalcemia. Data analysis revealed a correlation between transient postoperative hypocalcemia and 25-hydroxyvitaminD levels: our work points towards the possibility to stratify the risk of transient postoperative hypocalcemia according to patients' preoperative 25-hydroxyvitaminD status.


Assuntos
Hipocalcemia , Tireoidectomia , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Hormônio Paratireóideo , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Vitamina D/análogos & derivados
20.
J Clin Med ; 10(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34640469

RESUMO

Whether to conduct remnant ablation or adjuvant radioactive iodine (RAI) therapy in patients with intrathyroidal differentiated thyroid carcinoma (DTC), sized 1.1-4 cm, is debated. We evaluated the impact of RAI on outcome in this category of DTCs. We retrospectively enrolled 308 patients submitted to total thyroidectomy: 198 had tumors sized 1.1-2 cm (Group 1) and 110 of 2.1-4 cm (Group 2). Both groups were divided into patients receiving and not receiving RAI after surgery. RAI+ and RAI- patients did not significantly differ, regarding several clinical and pathological features. Final outcome was defined according to dynamic risk stratification. Remission was observed in the majority of Group 1 and Group 2 patients and outcome did not significantly differ between RAI+ and RAI- patients: respectively, 95.8% vs. 93.7% in Group 1, and 87.7% vs. 86.5% in Group 2. The majority of persistent cases, either RAI+ or RAI-, received therapeutic RAI administration, and about 50% of RAI- cases had an excellent response at final follow up, whereas no RAI+ persistent patients had a beneficial effect. Our findings demonstrate that patients with an intrathyroidal DTC sized 1.1-4 cm do not benefit from RAI. The outcome of these patients remains favorable, and the few patients with persistent diseases can be treated with RAI during follow up.

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