7 research outputs found

    Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

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    Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

    Teamstepps Virtual Teams: Interactive Virtual Team Training And Practice For Health Professional Learners

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    Medical errors because of communication failure are common in health care settings. Teamwork training, such as Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), improves team performance and patient outcomes. Academic institutions seek high-quality, low-cost curricula for interprofessional education (IPE) to prepare learners for clinical experiences before and after graduation; however, most IPE curricula involve lectures, simple tabletop exercises, and in-person simulations and are not readily accessible to geographically distributed and asynchronously engaged learners. To address this need, interprofessional faculty from multiple institutions and specialties created a series of eight screen-based interactive virtual simulation cases featuring typical clinical situations, with the goal of preparing learners to provide safe and effective care in clinical teams. Virtual simulations permit flexible, asynchronous learning on the learner\u27s schedule and allow educators an opportunity to identify gaps in knowledge and/or attitudes that can be addressed during class or forum discussions. In 2016, 1,128 unique users accessed the scenarios. As a result of such virtual activities, learner selection of the appropriate TeamSTEPPS tool increased with progression through the scenarios

    Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring

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    Intrauterine growth restriction and accelerated postnatal growth predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal growth, but also impairs mammary development and postnatal growth. We used cross-fostering to compare the influence of prenatal and postnatal nutritional restraint on adult glucose tolerance, insulin secretion, insulin sensitivity and hypothalamic NPY content in WKY rats at 6 months of age. Bilateral uterine vessel ligation (Restricted) to induce uteroplacental insufficiency or sham surgery (Control) was performed on day 18 of gestation. Control, Restricted and Reduced (reducing litter size of Controls to match Restricted) pups were cross-fostered onto a Control or Restricted mother 1 day after birth. Restricted pups were born small compared to Controls. Restricted males, but not females, remained lighter up to 6 months, irrespective of postnatal environment. By 10 weeks, Restricted-on-Restricted males ate more than Controls. At 6 months Restricted-on-Restricted males had increased hypothalamic NPY content compared to other groups and together with Reduced-on-Restricted males had increased retroperitoneal fat weight (% body weight) compared to Control-on-Controls. Restricted-on-Restricted males had impaired glucose tolerance, reduced first-phase insulin secretion, but unaltered insulin sensitivity, compared to Control-on-Controls. In males, being born small and exposed to an impaired lactational environment adversely affects adult glucose tolerance and first-phase insulin secretion, but improving lactation partially ameliorates this condition. This study identifies early life as a target for intervention to prevent later diabetes following prenatal restraint.Andrew L Siebel, Amy Mibus, Miles J De Blasio, Kerryn T Westcott, Margaret J Morris, Larissa Prior, Julie A Owens, and Mary E Wlode
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