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- Vergallo, A., et al.
(författare)
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Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 96, s. 22-32
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc.
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- Vergallo, A., et al.
(författare)
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Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:6, s. 764-775
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 7. |
- Mege, D, et al.
(författare)
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Surgical management of esophageal sarcoma: a multicenter European experience
- 2018
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Ingår i: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. - : Oxford University Press (OUP). - 1442-2050. ; 31:3
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal sarcomas are rare and evidence in literature is scarce making their management difficult. The objective is to report surgical and oncological outcomes of esophageal sarcoma in a large multicenter European cohort. This is a retrospective multicenter study including all patients who underwent en-bloc esophagectomy for esophageal sarcoma in seven European tertiary referral centers between 1987 and 2016. The main outcomes and measures are pathological results, early and long-term outcomes. Among 10,936 esophageal resections for cancer, 21 (0.2%) patients with esophageal sarcoma were identified. The majority of tumors was located in the middle (n = 7) and distal (n = 9) third of the esophagus. Neoadjuvant chemoradiotherapy was performed in five patients. All the patients underwent en-bloc transthoracic esophagectomy (19 open, 2 minimally invasive). Postoperative mortality occurred in 1 patient (5%). One patient received adjuvant chemotherapy. Definitive pathological results were carcinosarcoma (n = 7), leiomyosarcoma (n = 5), and other types of sarcoma (n = 9). Microscopic R1 resection was present in one patient (5%) and seven patients (33%) had positive lymph nodes. Median follow-up was 16 (3–79) months in 20 of 21 patients (95%). One-, 3-, and 5-year overall survival rates were 74%, 43%, and 35%, respectively. One-, 3- and 5-years disease-free survival rates were 58%, 40%, and 33%, respectively. Median overall survival was 6 months in N+ patients vs. 37 months for N0 patients (p = 0.06). At the end of the follow-up period, nine patients had died from cancer recurrences (43%), three patients died from other reasons (14%), one patient was still alive with recurrence (5%) and the seven remaining patients were free of disease (33%). Recurrence was local (n = 3), metastatic (n = 3), or both (n = 4). In conclusion, carcinosarcoma and leiomyosarcoma were the most common esophageal sarcoma histological subtypes. Lymph node involvement was seen in one third of cases. A transthoracic en-bloc esophagectomy with radical lymphadenectomy should be the best surgical option to achieve complete resection. Long-term survival remained poor with a high local and distant recurrence rate.
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