9 results on '"Guida, Melania"'
Search Results
2. National Multicenter Study on the Comparison of Robotic and Open Thymectomy for Thymic Neoplasms in Myasthenic Patients: Surgical, Neurological and Oncological Outcomes.
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Sicolo, Elisa, Zirafa, Carmelina Cristina, Romano, Gaetano, Brandolini, Jury, De Palma, Angela, Bongiolatti, Stefano, Gallina, Filippo Tommaso, Ricciardi, Sara, Maestri, Michelangelo, Guida, Melania, Morganti, Riccardo, Carleo, Graziana, Mugnaini, Giovanni, Tajè, Riccardo, Calabró, Fabrizia, Lenzini, Alessandra, Davini, Federico, Cardillo, Giuseppe, Facciolo, Francesco, and Voltolini, Luca
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EVALUATION of medical care , *LENGTH of stay in hospitals , *RESEARCH , *THYMUS tumors , *MYASTHENIA gravis , *SURGICAL robots , *SURGICAL complications , *CANCER patients , *HOSPITAL care , *DESCRIPTIVE statistics - Abstract
Simple Summary: Extended thymectomy is the gold standard in the treatment of patients with thymic neoplasm and affected by myasthenia gravis. For a long time, the traditional approach has been sternotomy, though the application of minimally invasive techniques has spread in recent decades. Several authors have demonstrated the safety and feasibility of minimally invasive thymectomy. This multicenter study aims to compare the outcomes of robotic and open thymectomy in myasthenic patients affected by thymic tumors. Short-term and long-term results were presented, showing how the robotic approach can be considered comparable to open surgery in terms of oncological radicality and the improvement of myasthenic symptomatology, with associated faster recovery. Thymectomy is the gold standard in the treatment of thymic neoplasm and plays a key role in the therapeutic path of myasthenia gravis. For years, sternotomy has been the traditional approach for removing anterior mediastinal lesions, although the robotic thymectomy is now widely performed. The literature is still lacking in papers comparing the two approaches and evaluating long-term oncological and neurological outcomes. This study aims to analyze the postoperative results of open and robotic thymectomy for thymic neoplasms in myasthenic patients. Surgical, oncological and neurological data of myasthenic patients affected by thymic neoplasms and surgically treated with extended thymectomy, both with the open and the robotic approach, in six Italian Thoracic Centers between 2011 and 2021 were evaluated. A total of 213 patients were enrolled in the study: 110 (51.6%) were treated with the open approach, and 103 (48.4%) were treated with robotic surgery. The open surgery, compared with the robotic, presented a shorter operating time (p < 0.001), a higher number of postoperative complications (p = 0.038) and longer postoperative hospitalization (p = 0.006). No other differences were observed in terms of surgical, oncological or neurological outcomes. The robotic approach can be considered safe and feasible, comparable to the open technique, in terms of surgical, oncological and neurological outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Thymectomy in severe (Myasthenia Gravis Foundation of America classes IV–V) generalized myasthenia gravis: is the game really worth the candle? A retrospective analysis from a multi-institutional database.
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Brascia, Debora, Lucchi, Marco, Aprile, Vittorio, Guida, Melania, Ricciardi, Roberta, Rea, Federico, Comacchio, Giovanni Maria, Schiavon, Marco, Marino, Maria Carlotta, Margaritora, Stefano, Meacci, Elisa, Spagni, Gregorio, Evoli, Amelia, Lorenzoni, Giulia, Iaco, Giulia De, Palma, Angela De, and Marulli, Giuseppe
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THYMECTOMY , *MYASTHENIA gravis , *VIDEO-assisted thoracic surgery , *DATABASES , *SURGICAL robots , *THORACIC surgery , *CHOLINERGIC receptors - Abstract
Open in new tab Download slide OBJECTIVES Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy. METHODS Data on 76 MG patients with preoperative MGFA classes IV and V who underwent thymectomy were retrospectively collected. Primary end points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA Post-Intervention Status criteria. RESULTS There were 27 (35.5%) males and 49 (64.5%) females; 53 (69.7%) were classified as MGFA class IV and 23 (30.3%) as class V. Thymectomy was performed through sternotomy in 25 (32.9%) patients, Video-assisted thoracic surgery (VATS) in 5 (6.6%) and Robot-assisted thoracic surgery (RATS) in 46 (60.5%). The median operative time was 120 (interquartile range: 95; 148) min. In-hospital mortality was observed in 1 (1.3%) patient and postoperative complications in 14 (18.4%) patients. The median postoperative hospital stay was 4 (interquartile range: 3; 6) days. Pathological examination revealed 31 (40.8%) thymic hyperplasia/other benign and 45 (59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5 years and 66.9% and 97.6% at 10 years, respectively. A significant improvement rate was found in patients with age at the time of thymectomy of ≤50 years (P = 0.0236), MGFA class V (P = 0.0154) and acetylcholine receptor antibodies positivity (P = 0.0152). CONCLUSIONS Thymectomy in patients with severe MG yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ MG. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis.
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Nicolì, Vanessa, Tabano, Silvia Maria, Colapietro, Patrizia, Maestri, Michelangelo, Ricciardi, Roberta, Stoccoro, Andrea, Fontana, Laura, Guida, Melania, Miozzo, Monica, Coppedè, Fabio, and Migliore, Lucia
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ANDROGEN receptors , *NEUROMUSCULAR diseases , *SEX discrimination , *MYASTHENIA gravis , *AUTOIMMUNE diseases , *YOUNG women , *NEUROMUSCULAR transmission , *X chromosome - Abstract
Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmunity. The skewed XCI pattern can lead to an unbalanced expression of some X-linked genes, as observed in several autoimmune disorders characterized by female predominance. No data are yet available regarding XCI and MG. We hypothesize that the preferential XCI pattern may contribute to the female bias observed in the onset of MG, especially among younger women. XCI analysis was performed on blood samples of 284 women between the ages of 20 and 82. XCI was tested using the Human Androgen Receptor Assay (HUMARA). XCI patterns were classified as random (XCI < 75%) and preferential (XCI ≥ 75%). In 121 informative patients, the frequency of skewed XCI patterns was 47%, significantly higher than in healthy controls (17%; p ≤ 0.00001). Interestingly, the phenomenon was observed mainly in younger patients (<45 years; p ≤ 0.00001). Furthermore, considering the XCI pattern and the other clinical characteristics of patients, no significant differences were found. In conclusion, we observed preferential XCI in MG female patients, suggesting its potential role in the aetiology of MG, as observed in other autoimmune diseases in women. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study.
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Chia, Ruth, Saez-Atienzar, Sara, Murphy, Natalie, Chiò, Adriano, Blauwendraat, Cornelis, Roda, Ricardo H., Tienari, Pentti J., Kaminski, Henry J., Ricciardi, Roberta, Guida, Melania, De Rosa, Anna, Petrucci, Loredana, Evoli, Amelia, Provenzano, Carlo, Drachman, Daniel B., and Traynor, Bryan J.
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MYASTHENIA gravis , *GENOME-wide association studies , *GENETIC correlations , *NICOTINIC receptors , *LOCUS (Genetics) - Abstract
Myasthenia gravis is a chronic autoimmune disease characterized by autoantibody-mediated interference of signal transmission across the neuromuscular junction. We performed a genome-wide association study (GWAS) involving 1,873 patients diagnosed with acetylcholine receptor antibody-positive myasthenia gravis and 36,370 healthy individuals to identify disease-associated genetic risk loci. Replication of the discovered loci was attempted in an independent cohort from the UK Biobank. We also performed a transcriptome-wide association study (TWAS) using expression data from skeletal muscle, whole blood, and tibial nerve to test the effects of disease-associated polymorphisms on gene expression. We discovered two signals in the genes encoding acetylcholine receptor subunits that are the most common antigenic target of the autoantibodies: a GWAS signal within the cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) gene and a TWAS association with the cholinergic receptor nicotinic beta 1 subunit (CHRNB1) gene in normal skeletal muscle. Two other loci were discovered on 10p14 and 11q21, and the previous association signals at PTPN22, HLA-DQA1/HLA-B, and TNFRSF11A were confirmed. Subgroup analyses demonstrate that early- and late-onset cases have different genetic risk factors. Genetic correlation analysis confirmed a genetic link between myasthenia gravis and other autoimmune diseases, such as hypothyroidism, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. Finally, we applied Priority Index analysis to identify potentially druggable genes/proteins and pathways. This study provides insight into the genetic architecture underlying myasthenia gravis and demonstrates that genetic factors within the loci encoding acetylcholine receptor subunits contribute to its pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Robotic thymectomy for thymoma in patients with myasthenia gravis: neurological and oncological outcomes.
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Romano, Gaetano, Zirafa, Carmelina Cristina, Ceccarelli, Ilaria, Guida, Melania, Davini, Federico, Maestri, Michelangelo, Morganti, Riccardo, Ricciardi, Roberta, Key, Teresa Hung, and Melfi, Franca
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THYMECTOMY , *MYASTHENIA gravis , *THYMOMA , *OVERALL survival , *SYMPTOMS , *TREATMENT effectiveness - Abstract
Open in new tab Download slide Open in new tab Download slide OBJECTIVES The goal of this study was to analyse the outcomes in 53 patients with thymoma, 34 of whom had myasthenia gravis (MG), who were treated with robotic surgery. The oncological outcomes of the whole series of patients were analysed. Furthermore, because consistent data are not yet available in the literature, the main focus was the analysis of the neurological results of the patients affected by MG and thymoma. METHODS The clinical outcomes of 53 patients with a diagnosis of thymoma who underwent robotic thymectomy between January 2014 and December 2019 in our institution were collected and evaluated; 34 of these patients had a concomitant diagnosis of MG. The neurological status of the patients was determined from a clinical evaluation according to the Osserman classification and on pre- and post-surgery Myasthenia Gravis Composite scores, whereas neurological clinical outcomes were assessed using the Myasthenia Gravis Foundation of America Post-Intervention Score. Reduction of steroid therapy was also considered. The recurrence rate, adjuvant radiotherapy and overall survival of the patients with a thymoma were evaluated. RESULTS Neurological outcomes: improvement of the clinical conditions was obtained in 26 patients (76.5%) following the operation: complete stable remission was observed in 5 patients (14.7%), pharmacological remission in 10 (29.4%) and minimal manifestation in 11 (32.3%). Four patients (11.8%) exhibited no substantial change from the pretreatment clinical manifestations or reduction in MG medication and 4 (11.8%) patients experienced worsening of clinical conditions. In 21 patients (61.7%) a reduction of the dosage of steroid therapy was obtained. Oncological outcomes: at an average follow-up of 36 months, the overall survival was 96%, 4 patients (7.5%) had pleural relapses and 12 patients (22.6%) underwent postoperative radiotherapy, according to their stage. In accordance with Masaoka staging, 34% were in stage I, 56.6% in stage II and 9.4% in stage III CONCLUSIONS Our results suggest that robotic surgical treatment of patients with thymoma and concomitant MG is effective in improving the neurological outcomes. Moreover, the oncological results obtained in this series confirm the efficacy of robotic surgery for the treatment of thymic malignancies, with results in line with those of open surgery. However, due to the indolent growth of thymomas, further observations with longer follow-up are necessary. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Thymoma‐associated myasthenia gravis: Clinical features and predictive value of antiacetylcholine receptor antibodies in the risk of recurrence of thymoma.
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De Rosa, Anna, Fornili, Marco, Maestri Tassoni, Michelangelo, Guida, Melania, Baglietto, Laura, Petrucci, Loredana, Chella, Antonio, Melfi, Franca, Lucchi, Marco, and Ricciardi, Roberta
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THYMUS surgery , *CHOLINERGIC receptors , *AGE distribution , *THORACIC surgery , *MYASTHENIA gravis , *REGRESSION analysis , *SEX distribution , *DISEASE relapse , *PRE-tests & post-tests , *PROPORTIONAL hazards models , *RETROSPECTIVE studies , *THYMOMA , *DESCRIPTIVE statistics , *DISEASE complications - Abstract
Background: Thymoma‐associated myasthenia gravis (TAMG) is one of the subtypes of myasthenia gravis with autoantibodies against the acetylcholine receptor (AChR‐Ab). We analyzed the clinical features of our cohort of TAMG patients and the changes in AChR‐Ab titer before and after thymectomy in order to identify factors predicting thymoma relapses. Methods: We retrospectively assessed: age of MG onset, MG clinical status according to MGFA (Myasthenia Gravis Foundation of America), epoch of thymectomy, post‐thymectomy status, oncological features and surgical approach. AChR‐Ab dosages were measured both before and after thymectomy. Linear regression models were applied to identify clinical determinants of AChR‐Ab titers and the Cox regression model was fitted to estimate the factors associated with the risk of thymoma recurrence. Results: The study sample included 239 MG patients, 27 of whom experienced one or more recurrences (median follow‐up time: 4.8 years). The AChR‐Ab titers decreased after first thymectomy (P < 0.001); the decrease was more pronounced in female patients (P = 0.05), in patients diagnosed with MG at an older age (P = 0.003), and in those who had lower MG stage before surgery (P = 0.02) or higher Masaoka‐Koga stage (P = 0.005). The risk of relapse was closely linked with the age of the patient, the Masaoka‐Koga stage and the surgical approach. Conclusions: Presurgery levels of AChR‐Ab or their change after surgery were not associated with thymoma recurrence. The reduction of AChR‐Ab titers after thymectomy confirms an immunological role of thymoma in the pathogenesis of MG. Key points: Significant findings of the study: Young MG patients with an advanced Masaoka staging score of the primary tumor who underwent thymectomy with approaches different from sternotomy and VATS should be monitored for high risk of recurrence.What this study adds: No other study has ever investigated the changes in AChR‐Ab titers before and after thymectomy in a large cohort of TAMG patients. The reduction of AChR‐Ab titers after thymectomy suggests an immunological role of thymoma in the pathogenesis of MG. [ABSTRACT FROM AUTHOR]
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- 2021
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8. The thymidylate synthase enhancer region (TSER) polymorphism increases the risk of thymic lymphoid hyperplasia in patients with Myasthenia Gravis.
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Lopomo, Angela, Ricciardi, Roberta, De Rosa, Anna, Guida, Melania, Maestri, Michelangelo, Lucchi, Marco, Melfi, Franca, Mussi, Alfredo, Migliore, Lucia, and Coppedè, Fabio
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HYPERPLASIA , *MYASTHENIA gravis , *THYMIDYLATE synthase , *GENE enhancers , *LYMPHOID tissue , *AUTOANTIBODIES , *NICOTINIC acetylcholine receptors , *GENETICS - Abstract
Background Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. Methods We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C > T, MTR c.2756A > G, MTRR c.66A > G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR + MG patients. A total of 526 AChR + MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. Results The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia ( P = 0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)]. Conclusions The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR + MG patients. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Investigation of GHSR methylation levels in thymomas from patients with Myasthenia Gravis.
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Coppedè, Fabio, Stoccoro, Andrea, Nicolì, Vanessa, Gallo, Roberta, De Rosa, Anna, Guida, Melania, Maestri, Michelangelo, Lucchi, Marco, Ricciardi, Roberta, and Migliore, Lucia
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GHRELIN receptors , *MYASTHENIA gravis , *P16 gene , *METHYLATION , *TUMOR suppressor genes , *EPITHELIAL tumors - Abstract
• We investigated GHSR methylation levels in thymomas from patients with Myasthenia Gravis. • GHSR hypermethylation was observed in 18 thymomas,28% of the total. • Samples showing GHSR hypermethylation were enriched in advanced disease stages than stage I. • GHSR hypermethylation is not a pan-cancer marker and is infrequent in encapsulated tumors. Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with Myasthenia Gravis (TAMG). In the present study we collected DNA samples from circulating lymphocytes and surgically resected tumor tissues of 65 TAMG patients, and from the adjacent healthy thymic tissue available from 43 of them. We then investigated GHSR methylation levels in the collected tissues searching for correlation with the clinical characteristics of the samples. GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 × 10−4), and those samples were particularly enriched in advanced disease stages than stage I (94% were in stage II or higher). GHSR was demethylated in the remaining 47 thymomas, as well as in all the investigated healthy thymic samples and in circulating lymphocytes. GHSR hypermethylation is not a pan-cancer marker or an early event in TAMG, but occurs in almost 1/4 of them and mainly from stage II onward. Subsequent studies are required to clarify the molecular pathways leading to GHSR hypermethylation in TAMG tissues and their relevance to disease progression. [ABSTRACT FROM AUTHOR]
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- 2020
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