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Recent developments in our understanding of molecular genetics have transformed screening and diagnostic practices for Lynch syndrome. The current standard involves universal tumour analysis of resected colorectal cancer (and ideally polypectomy) specimens using immunohistochemistry and molecular techniques. Patients with abnormal immunohistochemical findings are subsequently referred for definitive mutational testing. This review relates the molecular pathogenesis of Lynch syndrome to current immunohistochemistry‐based screening strategies and discusses the interpretation and clinical implications of screening results. 相似文献
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Benny Bjrkblom Carl Wibom Maria Eriksson A Tommy Bergenheim Rickard L Sjberg Pr Jonsson Thomas Brnnstrm Henrik Antti Maria Sandstrm Beatrice Melin 《Neuro-oncology》2022,24(9):1454
BackgroundGliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.MethodsCross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors—oligodendroglioma (n = 31), astrocytoma (n = 31) and glioblastoma (n = 162)—were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2–4, and MGMT promoter methylation.ResultsDistinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides, and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.ConclusionKey metabolic differences exist across adult glioma subtypes. 相似文献
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Ahmad Ramy Elashery John W. Rickard Sammy Zakaria 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2014,41(6):631-633
Vasovagal (neurocardiogenic) syncope, a subtype of reflex syncope, has many well-known triggers. However, we found no previous report of vasovagal exercise-induced syncope in a sedentary person. We present the case of a 35-year-old sedentary woman who experienced vasovagal syncope as she underwent an exercise stress test. Results of evaluations, including resting and stress electrocardiography and echocardiography, were normal. Her presentation is highly unusual: syncope has typically not been associated with exercise except in young athletes, people with structural heart abnormalities, or people with a prolonged QT syndrome. To our knowledge, this is the first report of vasovagal syncope associated with exercise in a sedentary patient who had normal cardiac and electrophysiologic function. We suggest possible physiologic mechanisms and diagnostic strategies. 相似文献
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Mandy Rickard Joana Dos Santos Johannes Keunen Armando J. Lorenzo 《Prenatal diagnosis》2022,42(9):1081-1093
Urinary tract dilation (UTD), including hydronephrosis (HN) is the most common prenatally detected anomaly and affects up to 1%–2% of pregnancies. Postnatally, it resolves without surgical intervention in approximately 75%–80% of children, however this may take several years to occur, necessitating repeated clinic visits and additional invasive testing for many. For the remainder, a surgical intervention will be offered to relieve obstruction or to correct vesicoureteral reflux. During the monitoring period, many of these infants will be offered continuous antibiotic prophylaxis for the prevention of urinary tract infections, however this remains a controversial topic among pediatric urologists and nephrologists. Herein, we present an up-to-date review of the early management of prenatally detected UTD including timing of postnatal imaging, the use of antibiotics, when circumcision may be beneficial and long term outcomes of the most common HN etiologies. We also propose a decision making tool to help guide the care of infants with UTD. 相似文献
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