22 results on '"Ferrante, E"'
Search Results
2. Disease control of acromegaly does not prevent excess mortality in the long term: results of a nationwide survey in Italy
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Arosio, M., Sciannameo, V., Contarino, A., Berchialla, P., Puglisi, S., Pesatori, A. C., Ferrante, E., Filopanti, M., Pivonello, R., Dassie, F., Rochira, V., Cannavò, S., De Menis, E., Pigliaru, F., Grottoli, S., Cambria, V., Faustini-Fustini, M., Montini, M., Peri, A., Ceccato, F., Puxeddu, E., Borretta, G., Bondanelli, M., Ferone, D., Colao, A., Terzolo, M., and Reimondo, G.
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- 2024
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3. A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas
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Basile, M, Valentini, Ilaria, Attanasio, R, Cozzi, R, Persichetti, A, Samperi, I, Scoppola, A, Auriemma, R, De Menis, E, Esposito, F, Ferrante, E, Iatì, G, Mazzatenta, D, Poggi, M, Rudà, R, Tortora, F, Cruciani, F, Mitrova, Z, Saulle, R, Vecchi, S, Cappabianca, P, Paoletta, A, Bozzao, A, Caputo, M, Doglietto, F, Ferraù, F, Lania, Ag, Laureti, S, Lello, S, Locatelli, D, Maffei, P, Minniti, G, Peri, A, Ruini, C, Settanni, F, Silvani, A, Veronese, N, Grimaldi, F, Papini, E, Cicchetti, A, Valentini, I (ORCID:0000-0001-5940-7495), Basile, M, Valentini, Ilaria, Attanasio, R, Cozzi, R, Persichetti, A, Samperi, I, Scoppola, A, Auriemma, R, De Menis, E, Esposito, F, Ferrante, E, Iatì, G, Mazzatenta, D, Poggi, M, Rudà, R, Tortora, F, Cruciani, F, Mitrova, Z, Saulle, R, Vecchi, S, Cappabianca, P, Paoletta, A, Bozzao, A, Caputo, M, Doglietto, F, Ferraù, F, Lania, Ag, Laureti, S, Lello, S, Locatelli, D, Maffei, P, Minniti, G, Peri, A, Ruini, C, Settanni, F, Silvani, A, Veronese, N, Grimaldi, F, Papini, E, Cicchetti, A, and Valentini, I (ORCID:0000-0001-5940-7495)
- Abstract
Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific data- bases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was euro2,558.91 and euro3,287.40 for subjects with micro- prolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after ini- tial treatment were euro798.13 and euro1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of euro3,201.15 compared to bromocriptine, based on a willingness-to-pay of euro40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic sur- gery was more cost-effective than cabergoline, with an ICER of euro44,846.64. Considering a willingness-to-pay of euro40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.
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- 2024
4. Determinants of outcome of transsphenoidal surgery for Cushing disease in a single-centre series
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Serban, A. L., Del Sindaco, G., Sala, E., Carosi, G., Indirli, R., Rodari, G., Giavoli, C., Locatelli, M., Carrabba, G., Bertani, G., Marfia, G., Mantovani, G., Arosio, M., and Ferrante, E.
- Abstract
Background: First-line therapy of Cushing disease (CD) is transsphenoidal surgery (TSS) aimed to obtain a complete removal of the pituitary adenoma and remission of disease. Purpose: To analyse the surgical outcome of patients with CD who underwent TSS in our Centre. Methods: Retrospective analysis on patients with CD who underwent TSS between 1990 and 2016. Results: We analysed 102 TSS that included: 84 first TSS and 18 second and third TSS. The overall remission rate after surgery was 76.5%, with a significant higher percentage of remitted patients after the first TSS compared to the subsequent TSS (82% vs 50%, p= 0.014). The remission after the first TSS was significantly higher when performed by a dedicated surgical team (DST) (89.8% vs 71% p= 0.04) and when the immunohistochemical examination confirmed the adrenocorticotropic adenoma (87% vs 55%, p= 0.04). Neuroradiological findings influenced the surgical outcome in a non-significant manner. Post-TSS complications were reported in 32 patients, with no significant variation when TSS was performed by DST. In case of reintervention, remission of disease was obtained in 72.7% of microadenoma, while no remitted patients were observed in case of macroadenomas. The DST did not significantly improve the outcome. Conclusion: Cushing disease is characterized by a broad spectrum of neuroradiological presentation. Despite the availability of a DST make the TSS a safe and effective first-line treatment among all these patients, a precise pre-treatment evaluation is needed in order to define the aim of neurosurgery and to schedule the management of recurrent disease.
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- 2024
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5. Interim analysis from prospective, multi-country, post-authorization safety study of patients with endogenous Cushing's syndrome treated with Ketoconazole HRA, using the existing European Registry on Cushing's syndrome (ERCUSYN), to assess safety and effectiveness
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Castinetti, F., Webb, S.M., Santos, A., Aulinas Maso, A., Zibar Tomsic, K., Amaral, C., Feelders, R., Ragnarsson, O., Ferrante, E., Ceccato, F., Chabre, O., Cristante, J., Hanzu, F., Reincke, M., Chanson, P., Tabarin, A., Duarte, J.S., Guelho, D., Fajardo, C., Rames, A., Bou Nader, M., Bertherat, J., and Brue, T.
- Abstract
Ketoconazole HRA is approved for endogenous Cushing's syndrome (CS). A post-authorization safety study (PASS) in 200 CS patients>12 years is ongoing to confirm Ketoconazole safety and effectiveness. Interim data are presented below.
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- 2024
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6. Who Are We Missing? Reporting of Ethnicity, Race, and Sex-Specific Populations in Clinical Trials.
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Kohn R, Sheu D, Britez Ferrante E, Lieberman A, Maitra MR, Drakes J, Stephens-Shields AJ, Okoh AK, Fanaroff AC, Morris AA, Ogunniyi MO, Dickert NW, Halpern SD, and Lane-Fall MB
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- 2024
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7. Hypopituitarism and COVID-19.
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Carosi G, Cremaschi A, Giavoli C, Ferrante E, and Mantovani G
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- Humans, Pituitary Gland, Pandemics, COVID-19 epidemiology, COVID-19 complications, Hypopituitarism etiology, SARS-CoV-2
- Abstract
Purpose: This review aims to collect and examine recent research findings regarding hypopituitarism and COVID-19, focusing on the virus's impact on the pituitary gland and the outcomes for infected patients with hormonal deficiencies., Methods: Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Pituitary" and "Hypopituitarism"., Results: Many studies have aimed to evaluate the function of the pituitary gland in infected patients, revealing variable degrees of deficiencies. The results are very heterogenous mostly because many different tests and hormonal cut-off have been adopted. It is unclear whether primary virus damage or the inflammatory response is responsible for these hormonal alterations. Interestingly, pituitary defects may persist long after the initial infection, possibly contributing to the "Long COVID syndrome". However, data on the recovery of pituitary function and long-term follow-up are not yet available. On the other hand, although findings are not consistent, patients with hypopituitarism may be at a higher risk for COVID-19 infection rate, complications, and mortality., Conclusion: The COVID-19 pandemic presented challenges for endocrinologists. The endocrine system appears to be involved in both the acute phase of infection and the recovery period. Hypopituitarism can be a consequence of SARS-COV-2 infection, and patients with existing hypopituitarism may face higher risks of complications. It is advisable to educate these patients on how to adjust their replacement therapies. Long-term follow-up data on pituitary function after recovery from COVID-19 are needed., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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8. Class imbalance on medical image classification: towards better evaluation practices for discrimination and calibration performance.
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Mosquera C, Ferrer L, Milone DH, Luna D, and Ferrante E
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- Humans, Calibration, Radiography, Thoracic standards, Radiography, Thoracic methods
- Abstract
Purpose: This work aims to assess standard evaluation practices used by the research community for evaluating medical imaging classifiers, with a specific focus on the implications of class imbalance. The analysis is performed on chest X-rays as a case study and encompasses a comprehensive model performance definition, considering both discriminative capabilities and model calibration., Materials and Methods: We conduct a concise literature review to examine prevailing scientific practices used when evaluating X-ray classifiers. Then, we perform a systematic experiment on two major chest X-ray datasets to showcase a didactic example of the behavior of several performance metrics under different class ratios and highlight how widely adopted metrics can conceal performance in the minority class., Results: Our literature study confirms that: (1) even when dealing with highly imbalanced datasets, the community tends to use metrics that are dominated by the majority class; and (2) it is still uncommon to include calibration studies for chest X-ray classifiers, albeit its importance in the context of healthcare. Moreover, our systematic experiments confirm that current evaluation practices may not reflect model performance in real clinical scenarios and suggest complementary metrics to better reflect the performance of the system in such scenarios., Conclusion: Our analysis underscores the need for enhanced evaluation practices, particularly in the context of class-imbalanced chest X-ray classifiers. We recommend the inclusion of complementary metrics such as the area under the precision-recall curve (AUC-PR), adjusted AUC-PR, and balanced Brier score, to offer a more accurate depiction of system performance in real clinical scenarios, considering metrics that reflect both, discrimination and calibration performance., Clinical Relevance Statement: This study underscores the critical need for refined evaluation metrics in medical imaging classifiers, emphasizing that prevalent metrics may mask poor performance in minority classes, potentially impacting clinical diagnoses and healthcare outcomes., Key Points: Common scientific practices in papers dealing with X-ray computer-assisted diagnosis (CAD) systems may be misleading. We highlight limitations in reporting of evaluation metrics for X-ray CAD systems in highly imbalanced scenarios. We propose adopting alternative metrics based on experimental evaluation on large-scale datasets., Competing Interests: Compliance with ethical standards Guarantor The scientific guarantor of this publication is Candelaria Mosquera. Conflict of interest At the time of submission, Candelaria Mosquera is employed by Abi Global Health. The other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry No complex statistical methods were necessary for this paper. Informed consent Written informed consent was not required for this study because we performed a retrospective analysis using publicly available datasets of chest X-ray images. Ethical approval Institutional Review Board approval was not required for this study because we performed a retrospective analysis using publicly available datasets of chest X-ray images. Study subjects or cohorts overlap The study subjects are those reported in the publicly available datasets CheXpert and ChestX-ray 14 (NIH). Methodology RetrospectiveExperimentalMulticenter study, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)
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- 2024
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9. Testosterone Therapy Does Not Affect Coagulation in Male Hypogonadism: A Longitudinal Study Based on Thrombin Generation.
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Lanzi V, Indirli R, Tripodi A, Clerici M, Bonomi M, Cangiano B, Petria I, Arosio M, Mantovani G, and Ferrante E
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- Humans, Male, Middle Aged, Longitudinal Studies, Aged, Adult, Prospective Studies, Case-Control Studies, Testosterone blood, Testosterone therapeutic use, Thrombin metabolism, Hypogonadism drug therapy, Hypogonadism blood, Hormone Replacement Therapy methods, Blood Coagulation drug effects
- Abstract
Context: Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking., Objective: This work aimed to compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls (HCs)., Methods: An observational prospective cohort study was conducted at 2 tertiary endocrinological ambulatory care centers. Patients included 38 men with hypogonadism (mean age 55 years, SD 13) and 38 age-matched HCs. Thrombin generation assay (TGA) was performed at T0 and T1 in hypogonadal men and in HCs. TGA is an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo. The following TGA parameters were recorded: lag time; thrombin-peak concentration; time-to-reach peak, velocity index, and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. Protein C, antithrombin, factor (F) VIII, and fibrinogen were assessed., Results: No changes in TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to HCs. Thrombin peak of hypogonadal men was significantly higher than HCs at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels., Conclusion: Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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10. Who and how to screen for endogenous hypercortisolism in patients with mood disorders.
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Ferrante E, Simeoli C, Mantovani G, and Pivonello R
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A strict association exists between mood disorders and endogenous hypercortisolism, namely Cushing's syndrome (CS). Indeed, CS is characterized by a wide range of mood disorders, such as major depression, generalized anxiety, panic disorders, bipolar disorders up to psychosis, with major depression being the most frequent, with a prevalence of 50-80%, and potentially representing the clinical onset of disease. Despite this observation, the exact prevalence of hypercortisolism in patients with mood disorders is unknown and who/how to screen for endogenous hypercortisolism among patients with mood disorders is still unclear. In this context, an accurate anamnestic and clinical examination are crucial in order to identify those patients who may benefit from CS screening. In particular, the presence of specific signs and symptoms of CS, comorbidities typically associated with CS, and lack of improvement of depressive symptoms with standard treatments can further guide the decision to screen for CS. Anyhow, it is noteworthy that mood disorders represent a cause of functional activation of hypothalamic-pituitary-adrenal (HPA) axis, a condition formerly known as non-neoplastic hypercortisolism (NNH). The differential diagnosis between CS and NNH is challenging. Beyond anamnestic and clinical features, various tests, including measurement of daily urinary cortisol and late-night salivary cortisol, together with low dose-dexamethasone suppression test, are used for initial screening. However, considering their low accuracy, a definitive diagnosis may require a longitudinal follow-up along with second-line dynamic tests like combined dexamethasone-CRH test and desmopressin test. In conclusion, available data suggest the need for a comprehensive assessment and follow-up of individuals with mood disorders to detect possible underlying CS, considering the pitfalls in diagnosis and the overlap of symptoms with other conditions like NNH. Specialized centers with expertise in CS diagnosis and differential testing are recommended for accurate evaluation and management of these patients., Competing Interests: Declarations Conflict of interest The authors have no competing interests to declare that are relevant to the content of this article. Research involving human participants and/or animals Not applicable. Informed consent Not applicable., (© 2024. The Author(s).)
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- 2024
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11. Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas.
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Esposito E, Marra G, Catalano R, Maioli S, Nozza E, Barbieri AM, Hantel C, Di Dalmazi G, Sigala S, Geginat J, Cassinotti E, Baldari L, Palmieri S, Mangone A, Berruti A, Ferrante E, Mantovani G, and Peverelli E
- Abstract
Filamin A (FLNA) is poorly expressed in adrenocortical carcinomas (ACC) compared to adenomas (ACA). Its presence is associated to a less aggressive tumour behaviour, potentially due to its role in negatively regulating IGF1R signalling. Upregulation of G2/M Wee1 kinase was shown in FLNA-deficient mouse neural progenitor cells, and it has been reported in several tumours. This study explored Wee1 expression in ACC and its regulation by FLNA, the effects of Wee1 inhibitor AZD1775, and the impact of FLNA on its efficacy in ACC cell lines and primary cells. Analysis of FLNA and Wee1 proteins revealed elevated Wee1 and reduced FLNA in ACC compared to normal adrenal gland. FLNA knockdown increased Wee1 protein in NCI-H295R, MUC-1, and in primary ACC cells. Higher p-CDK1 and cyclin B1 were shown in FLNA-silenced MUC-1, while decreased Wee1, p-CDK1 and cyclin B1 resulted after FLNA overexpression. Wee1 reduction was reverted by lactacystin treatment and FLNA transfection increased p-Wee1 (Ser123), suggesting FLNA's role in targeting Wee1 for degradation. AZD1775 dose-dependently reduced proliferation and viability in ACC cell lines and primary cultures, and it triggered MUC-1 cell death. Similar effects were induced by Wee1 silencing. FLNA depletion augmented AZD1775's efficacy in reducing proliferation and potentiating apoptosis in MUC-1 and primary cells. In conclusion, we demonstrated that FLNA regulates Wee1 expression by promoting its degradation, suggesting that low FLNA typical of ACC leads to increased Wee1 with consequent cancer cells growth. It proposes Wee1 inhibition as a new potential therapeutic approach for ACC, particularly for those lacking FLNA., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2024
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12. Macro-FSH is a rare cause of inappropriately high FSH concentrations.
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Mantovani B, Indirli R, Lanzi V, Petria I, Arosio M, Mantovani G, Somigliana E, Vidali M, Ceriotti F, and Ferrante E
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Summary: Assessment of hormone concentrations can be subjected to laboratory pitfalls. Macro-hormones are hormone-autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormones' concentrations. Macro-prolactin and macro-thyroid-stimulating hormone (TSH) are most frequently encountered while macro-follicle-stimulating hormone (FSH) has been rarely reported. We describe the case of a 30-year-old woman who had a gynaecological consultation due to failure in achieving pregnancy after 8 months of unprotected intercourse. She had regular menses, did not complain of climacteric symptoms and her medical history was unremarkable. Antral follicle count and anti-mullerian hormone concentrations were normal, and regular ovulation was documented. Unexpectedly, high early follicular phase FSH concentrations were confirmed on two occasions (57 and 51 IU/L), raising the suspicion of primary ovarian insufficiency. After excluding Turner's syndrome and autoimmune oophoritis, a laboratory artifact was hypothesized. Following polyethylene glycol precipitation, FSH levels dropped from 41.1 IU/L to 6.54 IU/L (recovery 16%) and the presence of macro-FSH was concluded. Laboratory interference can lead to misdiagnosis and unnecessary treatments. A laboratory artifact should be suspected when inconsistency exists between clinical presentation and laboratory results. Only five other cases of macro-FSH have been reported to date. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure., Learning Points: Hormone quantification is a cornerstone in the diagnostic workup of endocrine disorders, but it can be subjected to laboratory interferences which can lead to unnecessary investigations and inappropriate treatments. A laboratory artifact should be suspected when a discrepancy is observed between clinical presentation and laboratory results, when extremely unusual analyte concentrations are observed and when inconsistent results are obtained by different analytical methods. Macro-hormones are hormone-autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormone concentrations. Macro-prolactin and macro-TSH are most frequently encountered, while macro-FSH has been rarely reported. Macro-hormones can be detected by polyethylene glycol precipitation, gel filtration chromatography, or by using protein G or protein A columns. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure.
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- 2024
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13. DXA-derived lumbar bone strain index corrected for kyphosis is associated with vertebral fractures and trabecular bone score in acromegaly.
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Jaafar S, Cristofolini G, Morenghi E, Rinaudo L, Birtolo MF, Sala E, Ferrante E, Mungari R, Lavezzi E, Leonardi L, Ragucci P, Ulivieri FM, Balzarini L, Mantovani G, Lania AG, and Mazziotti G
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- Humans, Male, Female, Middle Aged, Aged, Adult, Acromegaly complications, Acromegaly physiopathology, Acromegaly diagnostic imaging, Spinal Fractures diagnostic imaging, Spinal Fractures etiology, Lumbar Vertebrae diagnostic imaging, Absorptiometry, Photon, Cancellous Bone diagnostic imaging, Kyphosis diagnostic imaging, Bone Density
- Abstract
Purpose: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly., Methods: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D)., Results: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563)., Conclusions: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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14. A model-free method to learn multiple skills in parallel on modular robots.
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van Diggelen F, Cambier N, Ferrante E, and Eiben AE
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Legged robots are well-suited for deployment in unstructured environments but require a unique control scheme specific for their design. As controllers optimised in simulation do not transfer well to the real world (the infamous sim-to-real gap), methods enabling quick learning in the real world, without any assumptions on the specific robot model and its dynamics, are necessary. In this paper, we present a generic method based on Central Pattern Generators, that enables the acquisition of basic locomotion skills in parallel, through very few trials. The novelty of our approach, underpinned by a mathematical analysis of the controller model, is to search for good initial states, instead of optimising connection weights. Empirical validation in six different robot morphologies demonstrates that our method enables robots to learn primary locomotion skills in less than 15 minutes in the real world. In the end, we showcase our skills in a targeted locomotion experiment., (© 2024. The Author(s).)
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- 2024
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15. High prevalence of hypercalcitoninemia in a large cohort of adult and paediatric patients with PTH resistance syndromes.
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Cremaschi A, Del Sindaco G, Pagnano A, Dolci A, Berkenou J, Rothenbuhler A, Contarino A, Ferrante E, Arosio M, Giannetta E, Linglart A, and Mantovani G
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Background: Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathormone (PTH) and other hormones now termed inactivating PTH/PTHrP disorders (iPPSD). Hypercalcitoninemia has been seldom reported in small series. Our aim was to investigate the characteristics of hypercalcitoninemia in paediatric and adult patients with PHP/iPPSD., Methods: We retrospectively collected data from two cohorts from two European Endocrinology tertiary centers: the paediatric cohort comprised 88 children with available calcitonin (CT) measurements; the adult cohort included 43 individuals with simultaneous CT and PTH measurements., Results: In the paediatric cohort 65.9% had hypercalcitoninemia (median CT 15 ng/L); in the adult cohort 53.5% (mean CT 21.6 ng/L). There was no difference between CT in paediatric and adult population; we observed stable CT levels over a median follow-up of 134.5 months in adults. Notably, no correlations were detected between CT and PTH levels. Other etiologies of hypercalcitoninemia were excluded, adult patients underwent regular thyroid ultrasound (US) to screen for medullary thyroid cancer (MTC). We performed 20 calcium stimulation tests in adult patients. While there was a significant difference in basal and peak CT between our patients, healthy subjects and subjects with MTC, there was no difference with patients with C-cell hyperplasia., Conclusions: This study underscores the common occurrence of hypercalcitoninemia in both paediatric and adult PHP/iPPSD patients, in particular with subtypes iPPSD2-iPPSD3. Furthermore, these patients show an hyperresponsiveness to calcium stimulation test falling between healthy subjects and patients with MTC. These findings contribute into the understanding of CT dynamics in the context of PHP/iPPSD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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16. Comparing Robot Controller Optimization Methods on Evolvable Morphologies.
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van Diggelen F, Ferrante E, and Eiben AE
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- Gait, Humans, Computer Simulation, Artificial Intelligence, Robotics methods, Robotics instrumentation, Algorithms, Bayes Theorem
- Abstract
In this paper, we compare Bayesian Optimization, Differential Evolution, and an Evolution Strategy employed as a gait-learning algorithm in modular robots. The motivational scenario is the joint evolution of morphologies and controllers, where "newborn" robots also undergo a learning process to optimize their inherited controllers (without changing their bodies). This context raises the question: How do gait-learning algorithms compare when applied to various morphologies that are not known in advance (and thus need to be treated as without priors)? To answer this question, we use a test suite of twenty different robot morphologies to evaluate our gait-learners and compare their efficiency, efficacy, and sensitivity to morphological differences. The results indicate that Bayesian Optimization and Differential Evolution deliver the same solution quality (walking speed for the robot) with fewer evaluations than the Evolution Strategy. Furthermore, the Evolution Strategy is more sensitive for morphological differences (its efficacy varies more between different morphologies) and is more subject to luck (repeated runs on the same morphology show greater variance in the outcomes)., (© 2023 Massachusetts Institute of Technology.)
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- 2024
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17. CheXmask: a large-scale dataset of anatomical segmentation masks for multi-center chest x-ray images.
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Gaggion N, Mosquera C, Mansilla L, Saidman JM, Aineseder M, Milone DH, and Ferrante E
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- Humans, Databases, Factual, Artificial Intelligence, Lung diagnostic imaging, Radiography, Thoracic
- Abstract
The development of successful artificial intelligence models for chest X-ray analysis relies on large, diverse datasets with high-quality annotations. While several databases of chest X-ray images have been released, most include disease diagnosis labels but lack detailed pixel-level anatomical segmentation labels. To address this gap, we introduce an extensive chest X-ray multi-center segmentation dataset with uniform and fine-grain anatomical annotations for images coming from five well-known publicly available databases: ChestX-ray8, CheXpert, MIMIC-CXR-JPG, Padchest, and VinDr-CXR, resulting in 657,566 segmentation masks. Our methodology utilizes the HybridGNet model to ensure consistent and high-quality segmentations across all datasets. Rigorous validation, including expert physician evaluation and automatic quality control, was conducted to validate the resulting masks. Additionally, we provide individualized quality indices per mask and an overall quality estimation per dataset. This dataset serves as a valuable resource for the broader scientific community, streamlining the development and assessment of innovative methodologies in chest X-ray analysis., (© 2024. The Author(s).)
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- 2024
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18. Operationalizing Equity, Inclusion, and Access in Research Practice at a Large Academic Institution.
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Britez Ferrante E, Blady S, Sheu D, Maitra MR, Drakes J, Lieberman A, Mussell A, Bair EF, Hearn CM, Thorbecke L, Zhu J, and Kohn R
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- Humans, Academic Medical Centers organization & administration, Academic Medical Centers standards, Biomedical Research standards
- Abstract
Introduction: Healthcare advances are hindered by underrepresentation in prospective research; sociodemographic, data, and measurement infidelity in retrospective research; and a paucity of guidelines surrounding equitable research practices., Objective: The Joint Research Practices Working Group was created in 2021 to develop and disseminate guidelines for the conduct of inclusive and equitable research., Methods: Volunteer faculty and staff from two research centers at the University of Pennsylvania initiated a multi-pronged approach to guideline development, including literature searches, center-level feedback, and mutual learning with local experts., Results: We developed guidelines for (1) participant payment and incentives; (2) language interpretation and translation; (3) plain language in research communications; (4) readability of study materials; and (5) inclusive language for scientific communications. Key recommendations include (1) offer cash payments and multiple payment options to participants when required actions are completed; (2) identify top languages of your target population, map points of contact, and determine available interpretation and translation resources; (3) assess reading levels of materials and simplify language, targeting 6th- to 8th-grade reading levels; (4) improve readability through text formatting and style, symbols, and visuals; and (5) use specific, humanizing terms as adjectives rather than nouns., Conclusions: Diversity, inclusion, and access are critical values for research conduct that promotes justice and equity. These values can be operationalized through organizational commitment that combines bottom-up and top-down approaches and through partnerships across organizations that promote mutual learning and synergy. While our guidelines represent best practices at one time, we recognize that practices evolve and need to be evaluated continuously for accuracy and relevance. Our intention is to bring awareness to these critical topics and form a foundation for important conversations surrounding equitable and inclusive research practices., (© 2023. The Author(s).)
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- 2024
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19. The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells.
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Di Muro G, Catalano R, Treppiedi D, Barbieri AM, Mangili F, Marra G, Di Bari S, Esposito E, Nozza E, Lania AG, Ferrante E, Locatelli M, Modena D, Steinkuhler C, Peverelli E, and Mantovani G
- Subjects
- Humans, Octreotide pharmacology, Octreotide therapeutic use, Receptors, Somatostatin genetics, Antimitotic Agents, Neuroendocrine Tumors drug therapy, Pituitary Neoplasms drug therapy, Pituitary Neoplasms genetics
- Abstract
Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984's antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (-40.8 (17.08)%, p < 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p < 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.
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- 2024
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20. Assessing robustness and generalization of a deep neural network for brain MS lesion segmentation on real-world data.
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Chaves H, Serra MM, Shalom DE, Ananía P, Rueda F, Osa Sanz E, Stefanoff NI, Rodríguez Murúa S, Costa ME, Kitamura FC, Yañez P, Cejas C, Correale J, Ferrante E, Fernández Slezak D, and Farez MF
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- Humans, Neural Networks, Computer, Algorithms, Brain diagnostic imaging, Brain pathology, Magnetic Resonance Imaging methods, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology
- Abstract
Objectives: Evaluate the performance of a deep learning (DL)-based model for multiple sclerosis (MS) lesion segmentation and compare it to other DL and non-DL algorithms., Methods: This ambispective, multicenter study assessed the performance of a DL-based model for MS lesion segmentation and compared it to alternative DL- and non-DL-based methods. Models were tested on internal (n = 20) and external (n = 18) datasets from Latin America, and on an external dataset from Europe (n = 49). We also examined robustness by rescanning six patients (n = 6) from our MS clinical cohort. Moreover, we studied inter-human annotator agreement and discussed our findings in light of these results. Performance and robustness were assessed using intraclass correlation coefficient (ICC), Dice coefficient (DC), and coefficient of variation (CV)., Results: Inter-human ICC ranged from 0.89 to 0.95, while spatial agreement among annotators showed a median DC of 0.63. Using expert manual segmentations as ground truth, our DL model achieved a median DC of 0.73 on the internal, 0.66 on the external, and 0.70 on the challenge datasets. The performance of our DL model exceeded that of the alternative algorithms on all datasets. In the robustness experiment, our DL model also achieved higher DC (ranging from 0.82 to 0.90) and lower CV (ranging from 0.7 to 7.9%) when compared to the alternative methods., Conclusion: Our DL-based model outperformed alternative methods for brain MS lesion segmentation. The model also proved to generalize well on unseen data and has a robust performance and low processing times both on real-world and challenge-based data., Clinical Relevance Statement: Our DL-based model demonstrated superior performance in accurately segmenting brain MS lesions compared to alternative methods, indicating its potential for clinical application with improved accuracy, robustness, and efficiency., Key Points: • Automated lesion load quantification in MS patients is valuable; however, more accurate methods are still necessary. • A novel deep learning model outperformed alternative MS lesion segmentation methods on multisite datasets. • Deep learning models are particularly suitable for MS lesion segmentation in clinical scenarios., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)
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- 2024
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21. A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.
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Basile M, Valentini I, Attanasio R, Cozzi R, Persichetti A, Samperi I, Scoppola A, Auriemma RS, De Menis E, Esposito F, Ferrante E, Iatì G, Mazzatenta D, Poggi M, Rudà R, Tortora F, Cruciani F, Mitrova Z, Saulle R, Vecchi S, Cappabianca P, Paoletta A, Bozzao A, Caputo M, Doglietto F, Ferraù F, Lania AG, Laureti S, Lello S, Locatelli D, Maffei P, Minniti G, Peri A, Ruini C, Settanni F, Silvani A, Veronese N, Grimaldi F, Papini E, and Cicchetti A
- Abstract
Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma., Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies., Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost., Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that., Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources., (© 2024 The Authors.)
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- 2024
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22. Unsupervised ensemble-based phenotyping enhances discoverability of genes related to left-ventricular morphology.
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Bonazzola R, Ferrante E, Ravikumar N, Xia Y, Keavney B, Plein S, Syeda-Mahmood T, and Frangi AF
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Recent genome-wide association studies have successfully identified associations between genetic variants and simple cardiac morphological parameters derived from cardiac magnetic resonance images. However, the emergence of large databases, including genetic data linked to cardiac magnetic resonance facilitates the investigation of more nuanced patterns of cardiac shape variability than those studied so far. Here we propose a framework for gene discovery coined unsupervised phenotype ensembles. The unsupervised phenotype ensemble builds a redundant yet highly expressive representation by pooling a set of phenotypes learnt in an unsupervised manner, using deep learning models trained with different hyperparameters. These phenotypes are then analysed via genome-wide association studies, retaining only highly confident and stable associations across the ensemble. We applied our approach to the UK Biobank database to extract geometric features of the left ventricle from image-derived three-dimensional meshes. We demonstrate that our approach greatly improves the discoverability of genes that influence left ventricle shape, identifying 49 loci with study-wide significance and 25 with suggestive significance. We argue that our approach would enable more extensive discovery of gene associations with image-derived phenotypes for other organs or image modalities., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)
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- 2024
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