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Mei Yin Wong Katrina A. Andrews Benjamin G. Challis Soo‐Mi Park Carlo L. Acerini Eamonn R. Maher Ruth T. Casey 《Clinical endocrinology》2019,90(4):499-505
The succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”. 相似文献
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Moheet Asma M. Shapshak Angela H. Brissie Megan A. Abulhasan Yasser B. Brophy Gretchen M. Frontera Jennifer Hall Wiley R. John Sayona Kalanuria Atul A. Kumar Abhay Lele Abhijit V. Mainali Shraddha May Casey C. Mayer Stephan A. McCredie Victoria Silva Gisele S. Singh Jeffrey M. Steinberg Alexis Sung Gene Tesoro Eljim P. Yakhkind Aleksandra 《Neurocritical care》2020,33(1):13-19
Neurocritical Care - 相似文献
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Shaffer Paige M. Smelson David A. Gaba Ayorkor Casey Sheila C. 《International journal of mental health and addiction》2022,20(2):1046-1062
International Journal of Mental Health and Addiction - Little research has focused on systematically integrating clinical treatment within drug court settings (a type of specialty court, and the... 相似文献
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Treatment of vulvar lichen sclerosus with topical corticosteroids in children: a study of 72 children 下载免费PDF全文
Treatment of vulvar lichen sclerosus (VLS) in children by topical corticosteroids gives control of symptoms and some resolution of physical signs, but large studies are limited. We report the largest study of 72 prepubertal girls with VLS, 62 of whom were prospectively treated with daily application of an ultrapotent topical corticosteroid (UPTC), clobetasol propionate 0.05% ointment, for 3 months, with a follow‐up period of 4–8 years [the remaining 10 patients responded to mild to moderate potency topical corticosteroids (MPTCs)]. The results were compared with a retrospective study of 31 prepubertal girls with VLS treated with MPTCs. MPTCs led to symptom clearance in 32.2% of patients, whereas UPTC led to symptom clearance in 72.6% of patients. Improvement in clinical signs following UPTC occurred in 90.3% of children at 3 months, with total resolution of clinical signs occurring in 29.2% at the 4‐year follow‐up or at puberty. No serious adverse effects occurred with UPTC treatment. In children with VLS, UPTCs relieve symptoms, resolve signs and possibly prevent scarring. UPTCs should therefore be the treatment of choice for VLS in children. 相似文献
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Yi Gong Dakai Mu Shilpa Prabhakar Ann Moser Patricia Musolino JiaQian Ren Xandra O Breakefield Casey A Maguire Florian S Eichler 《Molecular therapy》2015,23(5):824-834
X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1) responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. We used recombinant adenoassociated virus serotype 9 (rAAV9) vector for delivery of the human ABCD1 gene (ABCD1) to mouse central nervous system (CNS). In vitro, efficient delivery of ABCD1 gene was achieved in primary mixed brain glial cells from Abcd1−/− mice as well as X-ALD patient fibroblasts. Importantly, human ABCD1 localized to the peroxisome, and AAV-ABCD1 transduction showed a dose-dependent effect in reducing VLCFA. In vivo, AAV9-ABCD1 was delivered to Abcd1−/− mouse CNS by either stereotactic intracerebroventricular (ICV) or intravenous (IV) injections. Astrocytes, microglia and neurons were the major target cell types following ICV injection, while IV injection also delivered to microvascular endothelial cells and oligodendrocytes. IV injection also yielded high transduction of the adrenal gland. Importantly, IV injection of AAV9-ABCD1 reduced VLCFA in mouse brain and spinal cord. We conclude that AAV9-mediated ABCD1 gene transfer is able to reach target cells in the nervous system and adrenal gland as well as reduce VLCFA in culture and a mouse model of X-ALD. 相似文献
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Fiene Marie Kuijper Uma V. Mahajan Seul Ku Daniel A.N. Barbosa Sheila M. Alessi Sherman C. Stein Kyle M. Kampman Brandon S. Bentzley Casey H. Halpern 《Neuromodulation》2022,25(2):253-262
ObjectivesCocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness.AimsWe conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs.Materials and MethodsQuality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline.ResultsOn a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively.ConclusionsWe find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy. 相似文献
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