37 results on '"Bergamino M"'
Search Results
2. Name-calling in the hippocampus (and beyond): coming to terms with neuron types and properties
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Hamilton, D. J., Wheeler, D. W., White, C. M., Rees, C. L., Komendantov, A. O., Bergamino, M., and Ascoli, G. A.
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- 2017
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3. Does hyper-progression exist among head and neck cancer patients treated with immunotherapy?
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Ortega Franco, A., primary, Plana, M., additional, Braña, I., additional, Taberna Sanz, M., additional, Oliva Bernal, M., additional, Vázquez, S., additional, Domenech Vinyolas, M., additional, Berenguer, G., additional, Vilajosana, E., additional, Bergamino, M., additional, Baste, N., additional, and Mesia Nin, R., additional
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- 2017
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4. Abstract P4-21-32: Treatment of early HER2-positive breast cancer in trastuzumab era in everyday clinical practice: An overview after 10 years of its approval
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Ortega, A, primary, Domenech, M, additional, Falo, C, additional, Gil, M, additional, Stradella, A, additional, Fernandez, A, additional, Morilla, I, additional, Villanueva, R, additional, Castany, R, additional, Vazquez, S, additional, Molina, K, additional, Bergamino, M, additional, Navarro, V, additional, and Pernas, S, additional
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- 2017
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5. Comorbidity and nutritional factors influence on bioradiotherapy (BRT) outcome in head and neck squamous cell carcinoma (HNSCC) patients
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Oliva, M., primary, Taberna, M., additional, Iriarte, A.J. Rullan, additional, Bergamino, M., additional, Rovira, A., additional, Montal, R., additional, Hurtos, L., additional, Arribas, L., additional, Vilajosana, E., additional, Lozano, A., additional, Navarro, V., additional, Vazquez, S., additional, Maños, M., additional, and Mesía, R., additional
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- 2016
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6. Recurrence pattern and its prognostic impact following definitive chemo-radiotherapy in stage III non-small cell lung cancer
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Morgui, M. Saigi, primary, Iriarte, A.J. Rullan, additional, Bergamino, M., additional, Navarro, A., additional, Arnaiz, M.M., additional, Palmero, R., additional, Serrahima, M. Plana, additional, Mesía, C., additional, Padrones, S., additional, Aso, S., additional, Rodriguez, J. Ruffinelli, additional, Navarro, V., additional, Brao, I., additional, Nadal, E., additional, and Alemany, F. Cardenal, additional
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- 2016
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7. Name-calling in the hippocampus (and beyond): coming to terms with neuron types and properties
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Hamilton, D. J., primary, Wheeler, D. W., additional, White, C. M., additional, Rees, C. L., additional, Komendantov, A. O., additional, Bergamino, M., additional, and Ascoli, G. A., additional
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- 2016
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8. 1058P - Does hyper-progression exist among head and neck cancer patients treated with immunotherapy?
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Ortega Franco, A., Plana, M., Braña, I., Taberna Sanz, M., Oliva Bernal, M., Vázquez, S., Domenech Vinyolas, M., Berenguer, G., Vilajosana, E., Bergamino, M., Baste, N., and Mesia Nin, R.
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- 2017
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9. 1192P - Recurrence pattern and its prognostic impact following definitive chemo-radiotherapy in stage III non-small cell lung cancer
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Morgui, M. Saigi, Iriarte, A.J. Rullan, Bergamino, M., Navarro, A., Arnaiz, M.M., Palmero, R., Serrahima, M. Plana, Mesía, C., Padrones, S., Aso, S., Rodriguez, J. Ruffinelli, Navarro, V., Brao, I., Nadal, E., and Alemany, F. Cardenal
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- 2016
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10. 977P - Comorbidity and nutritional factors influence on bioradiotherapy (BRT) outcome in head and neck squamous cell carcinoma (HNSCC) patients
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Oliva, M., Taberna, M., Iriarte, A.J. Rullan, Bergamino, M., Rovira, A., Montal, R., Hurtos, L., Arribas, L., Vilajosana, E., Lozano, A., Navarro, V., Vazquez, S., Maños, M., and Mesía, R.
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- 2016
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11. 43P'Real world data' of genomic sequencing for personalised therapy.
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Bergamino, M S, Vethencourt, A, Stradella, A, Recalde, S, Fabregat, C, Vázquez, S, Falo, C, Fernández-Ortega, A, Vazquez, R Villanueva, and Cardona, M E Ferrer
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INDIVIDUALIZED medicine , *CANCER treatment , *TUMOR treatment - Published
- 2018
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12. Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
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Pamela Céliz, Meritxell Bellet, Agustí Barnadas, X. Perez Martin, Elena García-Martínez, Miguel Gil-Gil, Adela Fernández-Ortega, Serafin Morales, Patricia Villagrasa, Sonia Pernas, Milana Bergamino, Eva Ciruelos, M Melé, Luis Manso, Cristina Saura, Noelia Martínez-Jañez, Institut Català de la Salut, [Gil-Gil MJ, Bergamino M] Department of Medical Oncology, Institut Català d’Oncologia, IDIBELL, L’Hospitalet, Spain. [Bellet M, Saura C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Morales S] Department of Medical Oncology, Hospital Arnau de Vilanova, Lleida, Spain. [Barnadas A] Department of Medical Oncology, Hospital de Sant Pau, Barcelona, Spain. [Manso L] Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
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0301 basic medicine ,Oncology ,Cancer Research ,Survival ,Phase II study ,medicine.medical_treatment ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Mama - Càncer - Quimioteràpia ,long-term results ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Persones grans ,Elderly ,0302 clinical medicine ,Clinical trials ,Breast cancer ,Quimioteràpia ,Clinical endpoint ,Medicine ,Triple negative breast cancer ,Triple-negative breast cancer ,RC254-282 ,education.field_of_study ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Ejection fraction ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Clinical Trial ,Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,030220 oncology & carcinogenesis ,phase II study ,neoadjuvant chemotherapy ,medicine.medical_specialty ,diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Population ,cardiotoxicity ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,survival ,Neoadjuvant chemotherapy ,elderly ,Càncer de mama ,03 medical and health sciences ,pegylated liposomal doxorubicin ,Pegylated liposomal doxorubicin ,Internal medicine ,Chemotherapy ,education ,Long-term results ,Cardiotoxicity ,business.industry ,medicine.disease ,Regimen ,030104 developmental biology ,triple negative breast cancer ,Avaluació de resultats (Assistència sanitària) ,terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,business ,Assaigs clínics - Abstract
BackgroundThe CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS).MethodsIn this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed.ResultsBetween Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%).ConclusionAt 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity.Trial Registration NumberClinicalTrials.gov reference NCT00563953.
- Published
- 2021
13. Exploring white matter microstructural alterations in mild cognitive impairment: a multimodal diffusion MRI investigation utilizing diffusion kurtosis and free-water imaging.
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Nelson MR, Keeling EG, Stokes AM, and Bergamino M
- Abstract
Background: Mild Cognitive Impairment (MCI) is a transitional stage from normal aging to dementia, characterized by noticeable changes in cognitive function that do not significantly impact daily life. Diffusion MRI (dMRI) plays a crucial role in understanding MCI by assessing white matter integrity and revealing early signs of axonal degeneration and myelin breakdown before cognitive symptoms appear., Methods: This study utilized the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to compare white matter microstructure in individuals with MCI to cognitively normal (CN) individuals, employing advanced dMRI techniques such as diffusion kurtosis imaging (DKI), mean signal diffusion kurtosis imaging (MSDKI), and free water imaging (FWI)., Results: Analyzing data from 55 CN subjects and 46 individuals with MCI, this study found significant differences in white matter integrity, particularly in free water levels and kurtosis values, suggesting neuroinflammatory responses and microstructural integrity disruption in MCI. Moreover, negative correlations between Mini-Mental State Examination (MMSE) scores and free water levels in the brain within the MCI group point to the potential of these measures as early biomarkers for cognitive impairment., Conclusion: In conclusion, this study demonstrates how a multimodal advanced diffusion imaging approach can uncover early microstructural changes in MCI, offering insights into the neurobiological mechanisms behind cognitive decline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nelson, Keeling, Stokes and Bergamino.)
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- 2024
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14. Altered resting-state functional connectivity and dynamic network properties in cognitive impairment: an independent component and dominant-coactivation pattern analyses study.
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Bergamino M, Burke A, Sabbagh MN, Caselli RJ, Baxter LC, and Stokes AM
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Introduction: Cognitive impairment (CI) due to Alzheimer's disease (AD) encompasses a decline in cognitive abilities and can significantly impact an individual's quality of life. Early detection and intervention are crucial in managing CI, both in the preclinical and prodromal stages of AD prior to dementia., Methods: In this preliminary study, we investigated differences in resting-state functional connectivity and dynamic network properties between 23 individual with CI due to AD based on clinical assessment and 15 healthy controls (HC) using Independent Component Analysis (ICA) and Dominant-Coactivation Pattern (d-CAP) analysis. The cognitive status of the two groups was also compared, and correlations between cognitive scores and d-CAP switching probability were examined., Results: Results showed comparable numbers of d-CAPs in the Default Mode Network (DMN), Executive Control Network (ECN), and Frontoparietal Network (FPN) between HC and CI groups. However, the Visual Network (VN) exhibited fewer d-CAPs in the CI group, suggesting altered dynamic properties of this network for the CI group. Additionally, ICA revealed significant connectivity differences for all networks. Spatial maps and effect size analyses indicated increased coactivation and more synchronized activity within the DMN in HC compared to CI. Furthermore, reduced switching probabilities were observed for the CI group in DMN, VN, and FPN networks, indicating less dynamic and flexible functional interactions., Discussion: The findings highlight altered connectivity patterns within the DMN, VN, ECN, and FPN, suggesting the involvement of multiple functional networks in CI. Understanding these brain processes may contribute to developing targeted diagnostic and therapeutic strategies for CI due to AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bergamino, Burke, Sabbagh, Caselli, Baxter and Stokes.)
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- 2024
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15. White Matter Microstructural Differences between Essential Tremor and Parkinson Disease, Evaluated Using Advanced Diffusion MRI Biomarkers.
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Bergamino M, Aslam S, Knittel JJ, Alhilali L, and Stokes AM
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- Humans, Biomarkers, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Essential Tremor diagnostic imaging, Parkinson Disease diagnostic imaging, White Matter diagnostic imaging
- Abstract
Background: Essential tremor (ET) is a common slowly-progressive neurologic disorder. It is predominantly characterized by kinetic tremors involving bilateral upper limbs. Although ET shares motor similarities with Parkinson disease (PD), there is no known relationship between ET and PD., Methods: We studied white matter differences between 17 ET and 68 PD patients using standard diffusion tensor imaging and fixel-based analysis (FBA). Diffusion magnetic resonance imaging data were acquired from two scanners (General Electric (GE) and Philips) with different numbers of diffusion directions. Fractional anisotropy maps were generated by the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL), and FBA was performed using MRtrix3 to obtain fiber density, fiber bundle, and fiber density bundle cross-section., Results: Compared with PD, significantly lower values of fiber density, fiber bundle, and fiber density bundle cross-section were found in the corpus callosum and left tapetum of the ET group. Additionally, significantly lower functional anisotropy values were found in the ET compared to the PD group, principally in the corpus callosum, corona radiata, and cingulum. In conclusion, differences in white matter integrity between ET and PD were observed by both FBA-based metrics and diffusion tensor imaging., Conclusions: Advanced diffusion-based metrics may provide a better understanding of the white matter microstructural characteristics in disparate motor-associated diseases with different underlying phenotypes, such as ET and PD., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)
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- 2023
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16. Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study.
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Bergamino M, Keeling EG, Ray NJ, Macerollo A, Silverdale M, and Stokes AM
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Introduction: Parkinson's disease (PD) is an idiopathic disease of the central nervous system characterized by both motor and non-motor symptoms. It is the second most common neurodegenerative disease. Magnetic resonance imaging (MRI) can reveal underlying brain changes associated with PD., Objective: In this study, structural connectivity and white matter networks were analyzed by diffusion MRI and graph theory in a cohort of patients with PD and a cohort of healthy controls (HC) obtained from the Parkinson's Progression Markers Initiative (PPMI) database in a cross-sectional analysis. Furthermore, we investigated longitudinal changes in the PD cohort over 36 months., Result: Compared with the control group, participants with PD showed lower structural connectivity in several brain areas, including the corpus callosum, fornix, and uncinate fasciculus, which were also confirmed by a large effect-size. Additionally, altered connectivity between baseline and after 36 months was found in different network paths inside the white matter with a medium effect-size. Network analysis showed trends toward lower network density in PD compared with HC at baseline and after 36 months, though not significant after correction. Significant differences were observed in nodal degree and strength in several nodes., Conclusion: In conclusion, altered structural and network metrics in several brain regions, such as corpus callosum, fornix, and cingulum were found in PD, compared to HC. We also report altered connectivity in the PD group after 36 months, reflecting the impact of both PD pathology and aging processes. These results indicate that structural and network metrics might yield insight into network reorganization that occurs in PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bergamino, Keeling, Ray, Macerollo, Silverdale and Stokes.)
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- 2023
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17. Free-water imaging of the cholinergic basal forebrain and pedunculopontine nucleus in Parkinson's disease.
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Ray NJ, Lawson RA, Martin SL, Sigurdsson HP, Wilson J, Galna B, Lord S, Alcock L, Duncan GW, Khoo TK, O'Brien JT, Burn DJ, Taylor JP, Rea RC, Bergamino M, Rochester L, and Yarnall AJ
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- Humans, Diffusion Tensor Imaging, Cholinergic Agents, Water, Cholinergic Neurons, Parkinson Disease complications, Basal Forebrain diagnostic imaging, Pedunculopontine Tegmental Nucleus
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Free-water imaging can predict and monitor dopamine system degeneration in people with Parkinson's disease. It can also enhance the sensitivity of traditional diffusion tensor imaging (DTI) metrics for indexing neurodegeneration. However, these tools are yet to be applied to investigate cholinergic system degeneration in Parkinson's disease, which involves both the pedunculopontine nucleus and cholinergic basal forebrain. Free-water imaging, free-water-corrected DTI and volumetry were used to extract structural metrics from the cholinergic basal forebrain and pedunculopontine nucleus in 99 people with Parkinson's disease and 46 age-matched controls. Cognitive ability was tracked over 4.5 years. Pearson's partial correlations revealed that free-water-corrected DTI metrics in the pedunculopontine nucleus were associated with performance on cognitive tasks that required participants to make rapid choices (behavioural flexibility). Volumetric, free-water content and DTI metrics in the cholinergic basal forebrain were elevated in a sub-group of people with Parkinson's disease with evidence of cognitive impairment, and linear mixed modelling revealed that these metrics were differently associated with current and future changes to cognition. Free water and free-water-corrected DTI can index cholinergic degeneration that could enable stratification of patients in clinical trials of cholinergic interventions for cognitive decline. In addition, degeneration of the pedunculopontine nucleus impairs behavioural flexibility in Parkinson's disease, which may explain this region's role in increased risk of falls., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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18. Using whole-brain diffusion tensor analysis to evaluate white matter structural correlates of delayed visuospatial memory and one-week motor skill retention in nondemented older adults: A preliminary study.
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Lingo VanGilder J, Bergamino M, Hooyman A, Fitzhugh MC, Rogalsky C, Stewart JC, Beeman SC, and Schaefer SY
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- Aged, Brain, Diffusion Tensor Imaging methods, Humans, Learning, Middle Aged, Motor Skills, White Matter diagnostic imaging, White Matter pathology
- Abstract
Skill retention is important for motor rehabilitation outcomes. Recent work has demonstrated that delayed visuospatial memory performance may predict motor skill retention in older and neuropathological populations. White matter integrity between parietal and frontal cortices may explain variance in upper-extremity motor learning tasks and visuospatial processes. We performed a whole-brain analysis to determine the white matter correlates of delayed visuospatial memory and one-week motor skill retention in nondemented older adults. We hypothesized that better frontoparietal tract integrity would be positively related to better behavioral performance. Nineteen participants (age>58) completed diffusion-weighted imaging, then a clinical test of delayed visuospatial memory and 50 training trials of an upper-extremity motor task; participants were retested on the motor task one week later. Principal component analysis was used to create a composite score for each participant's behavioral data, i.e. shared variance between delayed visuospatial memory and motor skill retention, which was then entered into a voxel-based regression analysis. Behavioral results demonstrated that participants learned and retained their skill level after a week of no practice, and their delayed visuospatial memory score was positively related to the extent of skill retention. Consistent with previous work, neuroimaging results indicated that regions within bilateral anterior thalamic radiations, corticospinal tracts, and superior longitudinal fasciculi were related to better delayed visuospatial memory and skill retention. Results of this study suggest that the simple act of testing for specific cognitive impairments prior to therapy may identify older adults who will receive little to no benefit from the motor rehabilitation regimen, and that these neural regions may be potential targets for therapeutic intervention., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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19. Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans.
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Martínez-Fernández C, Bergamino M, Schiavi A, Brena D, Ventura N, Honnen S, Villanueva A, Nadal E, and Cerón J
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- Animals, Cisplatin toxicity, Mitochondria drug effects, Mitochondria metabolism, Mitochondrial Diseases chemically induced, Neurotoxicity Syndromes etiology, Oxidative Stress, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins metabolism
- Abstract
Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we used C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion. First, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse XFe96 Analyzer, we observed a detrimental effect of cisplatin and glucose on mitochondrial respiration. Second, because catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. Using a Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects against the dose-dependent neurotoxicity caused by cisplatin., Competing Interests: Competing interests E.N. received research support from Roche, Merck Serono, Bristol Myers Squibb and Pfizer, and participated in advisory boards or lectures from Bristol Myers Squibb, Merck Serono, Merck Sharpe & Dohme, Lilly, Roche, Pfizer, Takeda, Bayer, Boehringer Ingelheim, Amgen and AstraZeneca., (© 2022. Published by The Company of Biologists Ltd.)
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- 2022
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20. Analysis of Brain Structural Connectivity Networks and White Matter Integrity in Patients With Mild Cognitive Impairment.
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Bergamino M, Schiavi S, Daducci A, Walsh RR, and Stokes AM
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White matter integrity and structural connectivity may be altered in mild cognitive impairment (MCI), and these changes may closely reflect decline in specific cognitive domains. Multi-shell diffusion data in healthy control (HC, n = 31) and mild cognitive impairment (MCI, n = 19) cohorts were downloaded from the ADNI3 database. The data were analyzed using an advanced approach to assess both white matter microstructural integrity and structural connectivity. Compared with HC, lower intracellular compartment (IC) and higher isotropic (ISO) values were found in MCI. Additionally, significant correlations were found between IC and Montreal Cognitive Assessment (MoCA) scores in the MCI cohort. Network analysis detected structural connectivity differences between the two groups, with lower connectivity in MCI. Additionally, significant differences between HC and MCI were observed for global network efficiency. Our results demonstrate the potential of advanced diffusion MRI biomarkers for understanding brain changes in MCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bergamino, Schiavi, Daducci, Walsh and Stokes.)
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- 2022
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21. Evaluation of single bolus, dual-echo dynamic susceptibility contrast MRI protocols in brain tumor patients.
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Stokes AM, Bergamino M, Alhilali L, Hu LS, Karis JP, Baxter LC, Bell LC, and Quarles CC
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- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Brain Neoplasms blood supply, Brain Neoplasms diagnostic imaging, Cerebral Blood Volume, Cerebrovascular Circulation, Contrast Media administration & dosage, Magnetic Resonance Imaging
- Abstract
Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is adversely impacted by contrast agent leakage in brain tumors. Using simulations, we previously demonstrated that multi-echo DSC-MRI protocols provide improvements in contrast agent dosing, pulse sequence flexibility, and rCBV accuracy. The purpose of this study is to assess the in-vivo performance of dual-echo acquisitions in patients with brain tumors (n = 59). To verify pulse sequence flexibility, four single-dose dual-echo acquisitions were tested with variations in contrast agent dose, flip angle, and repetition time, and the resulting dual-echo rCBV was compared to standard single-echo rCBV obtained with preload (double-dose). Dual-echo rCBV was comparable to standard double-dose single-echo protocols (mean (standard deviation) tumor rCBV 2.17 (1.28) vs. 2.06 (1.20), respectively). High rCBV similarity was observed (CCC = 0.96), which was maintained across both flip angle (CCC = 0.98) and repetition time (CCC = 0.96) permutations, demonstrating that dual-echo acquisitions provide flexibility in acquisition parameters. Furthermore, a single dual-echo acquisition was shown to enable quantification of both perfusion and permeability metrics. In conclusion, single-dose dual-echo acquisitions provide similar rCBV to standard double-dose single-echo acquisitions, suggesting contrast agent dose can be reduced while providing significant pulse sequence flexibility and complementary tumor perfusion and permeability metrics.
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- 2021
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22. Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study.
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Gil-Gil MJ, Bellet M, Bergamino M, Morales S, Barnadas A, Manso L, Saura C, Fernández-Ortega A, Garcia-Martinez E, Martinez-Jañez N, Melé M, Villagrasa P, Celiz P, Perez Martin X, Ciruelos E, and Pernas S
- Abstract
Background: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS)., Methods: In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m
2 ) plus cyclophosphamide (600 mg/m2 ) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed., Results: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%)., Conclusion: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity., Trial Registration Number: ClinicalTrials.gov reference NCT00563953., Competing Interests: MG-G declares consulting/advisory fees from Pfizer, Daiichi-Sankyo, Novartis and Roche. MB declares consulting/advisory fees from Pfizer, Novartis and Lilly. SM declares consulting/advisory fees from Pfizer, Roche and Lilly. AB declares consulting/advisory fees from Pfizer, Roche, Bristol Muers Squibb, Astra-Zeneca and Lilly. CS declares consulting/advisory fees from Pfizer, Roche, Macrogenics, Piqur therapeutics, Puma, Synthon and Novartis. EG-M declares consulting/advisory fees from Roche; Astra-Zeneca, Clovis, Pharmamr, Celgene and Novartis. EC declares consulting/advisory fees from Puma, Pfizer, Roche, Astra-Zeneca, Celgene, Daiichi-Sankyo, Eisai, Genomyc Health, Novartis Pierre Fabre and Synthon. SP declares consulting/advisory fees from Astra-Zeneca, Daiichi-Sankyo, Novartis, Polyphor, Roche, and Seattle Genetics; and travel/accommodation grants from Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gil-Gil, Bellet, Bergamino, Morales, Barnadas, Manso, Saura, Fernández-Ortega, Garcia-Martinez, Martinez-Jañez, Melé, Villagrasa, Celiz, Perez Martin, Ciruelos and Pernas.)- Published
- 2021
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23. Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder.
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Zheng H, Bergamino M, Ford BN, Kuplicki R, Yeh FC, Bodurka J, Burrows K, Hunt PW, Teague TK, Irwin MR, Yolken RH, Paulus MP, and Savitz J
- Subjects
- Anisotropy, Diffusion Tensor Imaging, Humans, Cytomegalovirus Infections diagnostic imaging, Depressive Disorder, Major diagnostic imaging, White Matter diagnostic imaging
- Abstract
Major depressive disorder (MDD) is associated with reductions in white matter microstructural integrity as measured by fractional anisotropy (FA), an index derived from diffusion tensor imaging (DTI). The neurotropic herpesvirus, human cytomegalovirus (HCMV), is a major cause of white matter pathology in immunosuppressed populations but its relationship with FA has never been tested in MDD despite the presence of inflammation and weakened antiviral immunity in a subset of depressed patients. We tested the relationship between FA and HCMV infection in two independent samples consisting of 176 individuals with MDD and 44 healthy controls (HC) (Discovery sample) and 88 participants with MDD and 48 HCs (Replication sample). Equal numbers of HCMV positive (HCMV+) and HCMV negative (HCMV-) groups within each sample were balanced on ten different clinical/demographic variables using propensity score matching. Anti-HCMV IgG antibodies were measured using a solid-phase ELISA. In the Discovery sample, significantly lower FA was observed in the right inferior fronto-occipital fasciculus (IFOF) in HCMV+ participants with MDD compared to HCMV- participants with MDD (cluster size 1316 mm
3 ; pFWE < 0.05, d = -0.58). This association was confirmed in the replication sample by extracting the mean FA from this exact cluster and applying the identical statistical model (p < 0.05, d = -0.45). There was no significant effect of diagnosis or interaction between diagnosis and HCMV in either sample. The effect of chronic HCMV infection on white matter integrity may-in at-risk individuals-contribute to the psychopathology of depression. These findings may provide a novel target of intervention for a subgroup of patients with MDD.- Published
- 2021
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24. Free-water diffusion tensor imaging improves the accuracy and sensitivity of white matter analysis in Alzheimer's disease.
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Bergamino M, Walsh RR, and Stokes AM
- Subjects
- Aged, Aged, 80 and over, Anisotropy, Biomarkers analysis, Cognitive Dysfunction diagnosis, Cognitive Dysfunction pathology, Humans, Middle Aged, Alzheimer Disease diagnosis, Alzheimer Disease pathology, Diffusion Magnetic Resonance Imaging methods, Diffusion Tensor Imaging methods, White Matter pathology
- Abstract
Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer's disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer's disease.
- Published
- 2021
- Full Text
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25. Systematic Assessment of the Impact of DTI Methodology on Fractional Anisotropy Measures in Alzheimer's Disease.
- Author
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Bergamino M, Keeling EG, Walsh RR, and Stokes AM
- Subjects
- Anisotropy, Corpus Callosum, Diffusion Tensor Imaging, Humans, Alzheimer Disease diagnostic imaging, Cognitive Dysfunction diagnostic imaging
- Abstract
White matter microstructural changes in Alzheimer's disease (AD) are often assessed using fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI). FA depends on the acquisition and analysis methods, including the fitting algorithm. In this study, we compared FA maps from different acquisitions and fitting algorithms in AD, mild cognitive impairment (MCI), and healthy controls (HCs) using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Three acquisitions from two vendors were compared (Siemens 30, GE 48, and Siemens 54 directions). DTI data were fit using nine fitting algorithms (four linear least squares (LLS), two weighted LLS (WLLS), and three non-linear LLS (NLLS) from four software tools (FSL, DSI-Studio, CAMINO, and AFNI). Different cluster volumes and effect-sizes were observed across acquisitions and fits, but higher consistency was observed as the number of diffusion directions increased. Significant differences were observed between HC and AD groups for all acquisitions, while significant differences between HC and MCI groups were only observed for GE48 and SI54. Using the intraclass correlation coefficient, AFNI-LLS and CAMINO-RESTORE were the least consistent with the other algorithms. By combining data across all three acquisitions and nine fits, differences between AD and HC/MCI groups were observed in the fornix and corpus callosum, indicating FA differences in these regions may be robust DTI-based biomarkers. This study demonstrates that comparisons of FA across aging populations could be confounded by variability in acquisitions and fit methodologies and that identifying the most robust DTI methodology is critical to provide more reliable DTI-based neuroimaging biomarkers for assessing microstructural changes in AD., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2021 by the authors.)
- Published
- 2021
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26. Assessing White Matter Pathology in Early-Stage Parkinson Disease Using Diffusion MRI: A Systematic Review.
- Author
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Bergamino M, Keeling EG, Mishra VR, Stokes AM, and Walsh RR
- Abstract
Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be impacted early in Parkinson disease (PD). Diffusion magnetic resonance imaging (dMRI) has been used extensively to understand such pathological WM changes, and the focus of this systematic review is to understand both the methods utilized and their corresponding results in the context of early-stage PD. Diffusion tensor imaging (DTI) is the most commonly utilized method to probe WM pathological changes. Previous studies have suggested that DTI metrics are sensitive in capturing early disease-associated WM changes in preclinical symptomatic regions such as olfactory regions and the substantia nigra, which is considered to be a hallmark of PD pathology and progression. Postprocessing analytic approaches include region of interest-based analysis, voxel-based analysis, skeletonized approaches, and connectome analysis, each with unique advantages and challenges. While DTI has been used extensively to study WM disorganization in early-stage PD, it has several limitations, including an inability to resolve multiple fiber orientations within each voxel and sensitivity to partial volume effects. Given the subtle changes associated with early-stage PD, these limitations result in inaccuracies that severely impact the reliability of DTI-based metrics as potential biomarkers. To overcome these limitations, advanced dMRI acquisition and analysis methods have been employed, including diffusion kurtosis imaging and q-space diffeomorphic reconstruction. The combination of improved acquisition and analysis in DTI may yield novel and accurate information related to WM-associated changes in early-stage PD. In the current article, we present a systematic and critical review of dMRI studies in early-stage PD, with a focus on recent advances in DTI methodology. Yielding novel metrics, these advanced methods have been shown to detect diffuse WM changes in early-stage PD. These findings support the notion of early axonal damage in PD and suggest that WM pathology may go unrecognized until symptoms appear. Finally, the advantages and disadvantages of different dMRI techniques, analysis methods, and software employed are discussed in the context of PD-related pathology., (Copyright © 2020 Bergamino, Keeling, Mishra, Stokes and Walsh.)
- Published
- 2020
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27. Corrigendum: PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution.
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Pernas S, Petit A, Climent F, Paré L, Perez-Martin J, Ventura L, Bergamino M, Galván P, Falo C, Morilla I, Fernandez-Ortega A, Stradella A, Rey M, Garcia-Tejedor A, Gil-Gil M, and Prat A
- Abstract
[This corrects the article DOI: 10.3389/fonc.2019.00707.]., (Copyright © 2019 Pernas, Petit, Climent, Paré, Perez-Martin, Ventura, Bergamino, Galván, Falo, Morilla, Fernandez-Ortega, Stradella, Rey, Garcia-Tejedor, Gil-Gil and Prat.)
- Published
- 2019
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28. PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution.
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Pernas S, Petit A, Climent F, Paré L, Perez-Martin J, Ventura L, Bergamino M, Galván P, Falo C, Morilla I, Fernandez-Ortega A, Stradella A, Rey M, Garcia-Tejedor A, Gil-Gil M, and Prat A
- Abstract
Introduction: HER2-enriched subtype has been associated with higher response to neoadjuvant anti-HER2-based therapy across various clinical trials. However, limited data exist in real-world practice and regarding residual disease. Here, we evaluate the association of HER2-enriched with pathological response (pCR) and gene expression changes in pre- and post-treatment paired samples in HER2-positive breast cancer patients treated outside of a clinical trial. Methods: We evaluated clinical-pathological data from a consecutive series of 150 patients with stage II-IIIC HER2-positive breast cancer treated from August 2004 to December 2012 with trastuzumab-based neoadjuvant chemotherapy. Expression of 105 breast cancer-related genes, including the PAM50 genes, was determined in available pre-and post-treatment formalin-fixed paraffin-embedded tumor samples using the nCounter platform. Intrinsic molecular subtypes were determined using the research-based PAM50 predictor. Association of genomic variables with total pCR was performed. Results: The pCR rate was 53.3%, with higher pCR among hormonal receptor (HR)-negative tumors (70 vs. 39%; P < 0.001). A total of 89 baseline and 28 residual tumors were profiled, including pre- and post-treatment paired samples from 26 patients not achieving a pCR. HER2-enriched was the predominant baseline subtype not only in the overall and HR-negative cohorts (64 and 75%, respectively), but also in the HR-positive cohort (55%). HER2-enriched was associated with higher pCR rates compared to non-HER2-enriched subtypes (65 vs. 31%; OR = 4.07, 95% CI 1.65-10.61, P < 0.002) and this association was independent of HR status. In pre- and post-treatment paired samples from patients not achieving a pCR, a lower proportion of HER2-enriched and twice the number of luminal tumors were observed at baseline, and luminal A was the most frequent subtype in residual tumors. Interestingly, most (81.8%) HER2-enriched tumors changed to non-HER2-enriched, whereas most luminal A samples maintained the same subtype in residual tumors. Conclusions: Outside of a clinical trial, PAM50 HER2-enriched subtype predicts pCR beyond HR status following trastuzumab-based chemotherapy in HER2-positive disease. The clinical value of intrinsic molecular subtype in residual disease warrants further investigation.
- Published
- 2019
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29. Fasting plasma glucose is an independent predictor of survival in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.
- Author
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Bergamino M, Rullan AJ, Saigí M, Peiró I, Montanya E, Palmero R, Ruffinelli JC, Navarro A, Arnaiz MD, Brao I, Aso S, Padrones S, Cardenal F, and Nadal E
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung therapy, Cohort Studies, Female, Follow-Up Studies, Humans, Lung Neoplasms mortality, Lung Neoplasms therapy, Male, Middle Aged, Predictive Value of Tests, Prognosis, Survival Analysis, Treatment Outcome, Biomarkers analysis, Blood Glucose analysis, Carboplatin therapeutic use, Carcinoma, Non-Small-Cell Lung diagnosis, Chemoradiotherapy, Lung Neoplasms diagnosis, Platinum therapeutic use
- Abstract
Background: Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy., Methods: One-hundred seventy patients with stage III NSCLC received definitive concurrent chemoradiotherapy from 2010 to 2014. Clinico-pathological data and clinical outcome was retrospectively registered. Fifty-six patients (33%), met criteria for type 2 diabetes mellitus (T2DM) at baseline. The prognostic value of FPG and other clinical variables was assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and Cox proportional models and log-rank test were used., Results: With a median follow-up of 36 months, median PFS was 8.0 months and median OS was 15.0 months in patients with FPG ≥7 mmol/L compared to 20 months (HR 1.13; 95% CI 1.07-1.19, p < 0.001) and 31 months (HR 1.09; 95% CI 1.04-1.15; p < 0.001) respectively, for patients with FPG < 7 mmol/L. In the multivariate analysis of the entire cohort adjusted by platinum compound and comorbidities, high levels of FPG as a continuous variable (HR 1.14; 95% CI 1.07-1.21; p < 0.001), the presence of comorbidity (HR 1.72; 95% CI 1.12-2.63; p = 0.012), and treatment with carboplatin (HR 1.95; 95% CI 1.26-2.99; p = 0.002) were independent predictors for shorter OS. In additional multivariate models considering non-diabetic patients as a reference group, diabetic patients with poor metabolic control (HbA1c > 8.5%) (HR 4.53; 95% CI 2.21-9.30; p < 0.001) and those receiving insulin (HR 3.22; 95% CI 1.90-5.46 p < 0.001) had significantly independent worse OS., Conclusion: Baseline FPG level is an independent predictor of survival in our cohort of patients with locally advanced NSCLC treated with concurrent chemoradiotherapy. Studies in larger cohorts of patients are warranted to confirm this relevant association.
- Published
- 2019
- Full Text
- View/download PDF
30. Comparison of two different analysis approaches for DTI free-water corrected and uncorrected maps in the study of white matter microstructural integrity in individuals with depression.
- Author
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Bergamino M, Kuplicki R, Victor TA, Cha YH, and Paulus MP
- Subjects
- Adult, Body Water diagnostic imaging, Female, Humans, Male, Psychiatric Status Rating Scales, Severity of Illness Index, Brain diagnostic imaging, Depressive Disorder, Major diagnostic imaging, Diffusion Tensor Imaging methods, Magnetic Resonance Imaging methods, White Matter diagnostic imaging
- Abstract
Diffusion tensor imaging (DTI) has often been used to examine white matter (WM) tract abnormalities in depressed subjects, but these studies have yielded inconsistent results, probably, due to gender composition or small sample size. In this study, we applied different analysis pipelines to a relatively large sample of individuals with depression to determine whether previous findings in depression can be replicated with these pipelines. We used a "standard" DTI algorithm and maps computed through a free-water (FW) corrected DTI. This latter algorithm is able to identify and separate the effects of extracellular FW on DTI metrics. Additionally, skeletonized and WM voxel-based analysis (VBA) methods were used. Using the skeletonized method, DTI maps showed lower fractional anisotropy (FA) in depressed subjects in the left brain hemisphere, including the anterior thalamic radiation (ATR L), cortical spinal tract (CST L), inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus (SLF L). Differences in radial diffusivity (RD) were also found. For the VBA using RD, we found different results when we used FW uncorrected and corrected DTI metrics. Relative to the VBA approach, the skeletonized analysis was able to identify more clusters where WM integrity was altered in depressed individuals. Different significant correlations were found between RD and the Patient Health Questionnaire in the CST L, and SLF L. In conclusion, the skeletonized method revealed more clusters than the VBA and individuals with depression showed multiple WM abnormalities, some of which were correlated with disease severity Hum Brain Mapp 38:4690-4702, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
31. Thinner Cortex in Collegiate Football Players With, but not Without, a Self-Reported History of Concussion.
- Author
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Meier TB, Bellgowan PS, Bergamino M, Ling JM, and Mayer AR
- Subjects
- Adult, Athletes, Humans, Male, Young Adult, Brain Concussion complications, Brain Concussion diagnosis, Cerebral Cortex pathology, Football injuries, Self Report, Universities
- Abstract
Emerging evidence suggests that a history of sports-related concussions can lead to long-term neuroanatomical changes. The extent to which similar changes are present in young athletes is undetermined at this time. Here, we tested the hypothesis that collegiate football athletes with (n = 25) and without (n = 24) a self-reported history of concussion would have cortical thickness differences and altered white matter integrity relative to healthy controls (n = 27) in fronto-temporal regions that appear particularly susceptible to traumatic brain injury. Freesurfer software was used to estimate cortical thickness, fractional anisotropy was calculated in a priori white matter tracts, and behavior was assessed using a concussion behavioral battery. Groups did not differ in self-reported symptoms (p > 0.10) or cognitive performance (p > 0.10). Healthy controls reported significantly higher happiness levels than both football groups (all p < 0.01). Contrary to our hypothesis, no differences in fractional anisotropy were observed between our groups (p > 0.10). However, football athletes with a history of concussion had significantly thinner cortex in the left anterior cingulate cortex, orbital frontal cortex, and medial superior frontal cortex relative to healthy controls (p = 0.02, d = -0.69). Further, football athletes with a history of concussion had significantly thinner cortex in the right central sulcus and precentral gyrus relative to football athletes without a history of concussion (p = 0.03, d = -0.71). No differences were observed between football athletes without a history of concussion and healthy controls. These results suggest that previous concussions, but not necessarily football exposure, may be associated with cortical thickness differences in collegiate football athletes.
- Published
- 2016
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32. Longitudinal assessment of white matter abnormalities following sports-related concussion.
- Author
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Meier TB, Bergamino M, Bellgowan PS, Teague TK, Ling JM, Jeromin A, and Mayer AR
- Subjects
- Affect, Athletes, Athletic Injuries psychology, Brain Concussion etiology, Brain Concussion psychology, Cross-Sectional Studies, Diffusion Tensor Imaging methods, Female, Humans, Interview, Psychological, Longitudinal Studies, Male, Neural Pathways pathology, White Matter pathology, Young Adult, Athletic Injuries pathology, Brain pathology, Brain Concussion pathology
- Abstract
There is great interest in developing physiological-based biomarkers such as diffusion tensor imaging to aid in the management of concussion, which is currently entirely dependent on clinical judgment. However, the time course for recovery of white matter abnormalities following sports-related concussion (SRC) is unknown. We collected diffusion tensor imaging and behavioral data in forty concussed collegiate athletes on average 1.64 days (T1; n = 33), 8.33 days (T2; n = 30), and 32.15 days post-concussion (T3; n = 26), with healthy collegiate contact-sport athletes (HA) serving as controls (n = 46). We hypothesized that fractional anisotropy (FA) would be increased acutely and partially recovered by one month post-concussion. Mood symptoms were assessed using structured interviews. FA differences were assessed using both traditional and subject-specific analyses. An exploratory analysis of tau plasma levels was conducted in a subset of participants. Results indicated that mood symptoms improved over time post-concussion, but remained elevated at T3 relative to HA. Across both group and subject-specific analyses, concussed athletes exhibited increased FA in several white matter tracts at each visit post-concussion with no longitudinal evidence of recovery. Increased FA at T1 and T3 was significantly associated with an independent, real-world outcome measure for return-to-play. Finally, we observed a nonsignificant trend for reduced tau in plasma of concussed athletes at T1 relative to HA, with tau significantly increasing by T2. These results suggest white matter abnormalities following SRC may persist beyond one month and have potential as an objective biomarker for concussion outcome. Hum Brain Mapp 37:833-845, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
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33. Dynamic Contrast-Enhanced MRI in the Study of Brain Tumors. Comparison Between the Extended Tofts-Kety Model and a Phenomenological Universalities (PUN) Algorithm.
- Author
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Bergamino M, Barletta L, Castellan L, Mancardi G, and Roccatagliata L
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Retrospective Studies, Algorithms, Brain Neoplasms pathology, Contrast Media, Image Enhancement methods, Magnetic Resonance Imaging methods, Models, Biological
- Abstract
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a well-established technique for studying blood-brain barrier (BBB) permeability that allows measurements to be made for a wide range of brain pathologies, including multiple sclerosis and brain tumors (BT). This latter application is particularly interesting, because high-grade gliomas are characterized by increased microvascular permeability and a loss of BBB function due to the structural abnormalities of the endothelial layer. In this study, we compared the extended Tofts-Kety (ETK) model and an extended derivate class from phenomenological universalities called EU1 in 30 adult patients with different BT grades. A total of 75 regions of interest were manually drawn on the MRI and subsequently analyzed using the ETK and EU1 algorithms. Significant linear correlations were found among the parameters obtained by these two algorithms. The means of R (2) obtained using ETK and EU1 models for high-grade tumors were 0.81 and 0.91, while those for low-grade tumors were 0.82 and 0.85, respectively; therefore, these two models are equivalent. In conclusion, we can confirm that the application of the EU1 model to the DCE-MRI experimental data might be a useful alternative to pharmacokinetic models in the study of BT, because the analytic results can be generated more quickly and easily than with the ETK model.
- Published
- 2015
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- View/download PDF
34. Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression.
- Author
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Bergamino M, Pasternak O, Farmer M, Shenton ME, and Hamilton JP
- Subjects
- Adult, Algorithms, Anisotropy, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Water, Young Adult, Brain pathology, Depressive Disorder, Major pathology, Diffusion Magnetic Resonance Imaging methods, Diffusion Tensor Imaging methods, Stress, Psychological pathology, White Matter pathology
- Abstract
Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations of MDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior fronto-occipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD.
- Published
- 2015
- Full Text
- View/download PDF
35. Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.
- Author
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Bergamino M, Hamilton DJ, Castelletti L, Barletta L, and Castellan L
- Subjects
- Databases as Topic instrumentation, Health Information Management instrumentation, Humans, Internet, Brain Neoplasms, Consumer Health Information, Database Management Systems instrumentation, Health Information Management methods, User-Computer Interface
- Abstract
In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.0, while the graphical user interface was created using PHP and HTML, thus making it easily accessible through a web browser. This web-based approach allows for multiple institutions to potentially access the database. The BT Database can record brain tumor patient information (e.g. clinical features, anatomical attributes, and radiological characteristics) and be used for clinical and research purposes. Analytic tools to automatically generate statistics and different plots are provided. The BT Database is a free and powerful user-friendly tool with a wide range of possible clinical and research applications in neurology and neurosurgery. The BT Database graphical user interface source code and manual are freely available at http://tumorsdatabase.altervista.org., (© The Author(s) 2013.)
- Published
- 2015
- Full Text
- View/download PDF
36. Measurement of blood-brain barrier permeability with t1-weighted dynamic contrast-enhanced MRI in brain tumors: a comparative study with two different algorithms.
- Author
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Bergamino M, Saitta L, Barletta L, Bonzano L, Mancardi GL, Castellan L, Ravetti JL, and Roccatagliata L
- Abstract
The purpose of this study was to assess the feasibility of measuring different permeability parameters with T1-weighted dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in order to investigate the blood brain-barrier permeability associated with different brain tumors. The Patlak algorithm and the extended Tofts-Kety model were used to this aim. Twenty-five adult patients with tumors of different histological grades were enrolled in this study. MRI examinations were performed at 1.5 T. Multiflip angle, fast low-angle shot, and axial 3D T1-weighted images were acquired to calculate T1 maps, followed by a DCE acquisition. A region of interest was placed within the tumor of each patient to calculate the mean value of different permeability parameters. Differences in permeability measurements were found between different tumor grades, with higher histological grades characterized by higher permeability values. A significant difference in transfer constant (K (trans)) values was found between the two methods on high-grade tumors; however, both techniques revealed a significant correlation between the histological grade of tumors and their K (trans) values. Our results suggest that DCE acquisition is feasible in patients with brain tumors and that K (trans) maps can be easily obtained by these two algorithms, even if the theoretical model adopted could affect the final results.
- Published
- 2013
- Full Text
- View/download PDF
37. PLI: a web-based tool for the comparison of protein-ligand interactions observed on PDB structures.
- Author
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Gallina AM, Bisignano P, Bergamino M, and Bordo D
- Subjects
- Binding Sites, Drug Design, Internet, Ligands, Proteins metabolism, Databases, Protein, Proteins chemistry, Software
- Abstract
Motivation: A large fraction of the entries contained in the Protein Data Bank describe proteins in complex with low molecular weight molecules such as physiological compounds or synthetic drugs. In many cases, the same molecule is found in distinct protein-ligand complexes. There is an increasing interest in Medicinal Chemistry in comparing protein binding sites to get insight on interactions that modulate the binding specificity, as this structural information can be correlated with other experimental data of biochemical or physiological nature and may help in rational drug design., Results: The web service protein-ligand interaction presented here provides a tool to analyse and compare the binding pockets of homologous proteins in complex with a selected ligand. The information is deduced from protein-ligand complexes present in the Protein Data Bank and stored in the underlying database., Availability: Freely accessible at http://bioinformatics.istge.it/pli/.
- Published
- 2013
- Full Text
- View/download PDF
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