Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

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

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

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

A PHENOMENOLOGICAL STUDY OF THE LIVED EXPERIENCES OF UNDOCUMENTED LATINO STUDENTS TO ENROLL IN AND PERSIST AT A FOUR-YEAR PUBLIC HISPANIC-SERVING INSTITUTION IN TEXAS

Undocumented students in the United States are trapped in a myriad of completing federal, state, and local laws that impact their lives daily. While approximately 60,000 undocumented students graduate from high school each year, the college going rate for this population is substantially lower than their documented peers. Since President Obama signed the Deferred Action for Childhood Arrivals executive order, undocumented students have gained national attention. Despite this new focus on undocumented students few studies have been conducted to gain a deeper understanding of the live experiences of these students. Framed by Tinto’s (1993) Theory of Student Departure and Latino capital theories, this phenomenological dissertation study focused on the lived experiences of four students who attended a four-year Hispanic-Serving Institution in Texas. Through a series of interviews conducted during the 2013-2014 academic year, this study sought to answer the question: why have undocumented Latino students enrolled and persisted against the odds in the pursuit of their four-year college degree? Through a comparison of the themes against Tinto’s Student Integration Model capital theories, three findings emerged: (a) undocumented students were able to enroll in an institution of higher education by leveraging the capital they possessed; (b) the determination of the undocumented students was so great, it allowed them to overcome the obstacles in their way; (c) the undocumented students persisted because the university community provided support. Advisers: Brent Cejda and Richard Hoove

Impact of Individual Patient Profiles on Adherence to Guideline Directed Medical Therapy in Heart Failure With Reduced Ejection Fraction: VCOR-HF Study.

BACKGROUND: Multiple co-morbidities complicate initiation of medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Adherence to guidelines based on individual patient profiles is not well described. This paper examines the effect of individual patient profiles on guideline recommended therapies for HFrEF. METHODS: This was a prospective, observational, non-randomised study of hospitalised HFrEF patients over 30 days, from 2014 to 2017 in 16 hospitals. A previously developed algorithm-based guideline adherence score was used to determine adherence to key performance indicators: prescribing of beta blockers, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid-receptor antagonist (MRAs) for HFrEF patients and early outpatient and heart failure (HF) disease management program review. Patients were classified as low, moderate and excellent adherence to medical therapy. RESULTS: Of the 696 HFrEF patients, 69.1% (n=481) were male with an average age of 73.15 years (SD±14.5 years). At discharge, 64.6% (n=427) were prescribed an ACEI/ARB, 78.7% (n=525) a beta blocker and 45.3% (n=302) prescribed MRA. Based on individual patient profiles, 18.2% (n=107) of eligible patients received an outpatient clinic and HF disease management program review within 30 days and 41.5% (n=71) were prescribed triple therapy. Based on individual profiles, 13% (n=21) of patients received an excellent guideline adherence score. CONCLUSION: Individual patient profiles impact on adherence to guideline recommendations. Review in transitional care and prescribing of triple pharmacotherapy is suboptimal. Translational strategies to facilitate the implementation of guideline recommended therapies is warranted