Diagnosis of Acute Aortic Syndrome in the Emergency Department (DAShED) study: an observational cohort study of people attending the emergency department with symptoms consistent with acute aortic syndrome.

BACKGROUND: The diagnosis of acute aortic syndrome (AAS) is commonly delayed or missed in the ED. We describe characteristics of ED attendances with symptoms potentially associated with AAS, diagnostic performance of clinical decision tools (CDTs) and physicians and yield of CT aorta angiogram (CTA). METHODS: This was a multicentre observational cohort study of adults attending 27 UK EDs between 26 September 2022 and 30 November 2022, with potential AAS symptoms: chest, back or abdominal pain, syncope or symptoms related to malperfusion. Patients were preferably identified prospectively, but retrospective recruitment was also permitted. Anonymised, routinely collected patient data including components of CDTs, was abstracted. Clinicians treating prospectively identified patients were asked to record their perceived likelihood of AAS, prior to any confirmatory testing. Reference standard was radiological or operative confirmation of AAS. 30-day electronic patient record follow-up evaluated whether a subsequent diagnosis of AAS had been made and mortality. RESULTS: 5548 patients presented, with a median age of 55 years (IQR 37-72; n=5539). 14 (0.3%; n=5353) had confirmed AAS. 10/1046 (1.0%) patients in whom the ED clinician thought AAS was possible had AAS. 5/147 (3.4%) patients in whom AAS was considered the most likely diagnosis had AAS. 2/3319 (0.06%) patients in whom AAS was considered not possible did have AAS. 540 (10%; n=5446) patients underwent CT, of which 407 were CTA (7%). 30-day follow-up did not reveal any missed AAS diagnoses. AUROC (area under the receiver operating characteristic) curve for ED clinician AAS likelihood rating was 0.958 (95% CI 0.933 to 0.983, n=4006) and for individual CDTs were: Aortic Dissection Detection Risk Score (ADD-RS) 0.674 (95% CI 0.508 to 0.839, n=4989), AORTAs 0.689 (95% CI 0.527 to 0.852, n=5132), Canadian 0.818 (95% CI 0.686 to 0.951, n=5180) and Sheffield 0.628 (95% CI 0.467 to 0.788, n=5092). CONCLUSION: Only 0.3% of patients presenting with potential AAS symptoms had AAS but 7% underwent CTA. CDTs incorporating clinician gestalt appear to be most promising, but further prospective work is needed, including evaluation of the role of D-dimer. TRIAL REGISTRATION NUMBER: NCT05582967; NCT05582967.

Multicentre open label randomised controlled trial of immediate enhanced ambulatory ECG monitoring versus standard monitoring in acute unexplained syncope patients: the ASPIRED study.

INTRODUCTION: Diagnosing underlying arrhythmia in emergency department (ED) syncope patients is difficult. There is a evidence that diagnostic yield for detecting underlying arrhythmia is highest when cardiac monitoring devices are applied early, ideally at the index visit. This strategy has the potential to change current syncope management from low diagnostic yield Holter to higher yield ambulatory monitoring, reduce episodes of syncope, reduce risk of recurrence and its potential serious consequences, reduce hospital admissions, reduce overall health costs and increase quality of life by allowing earlier diagnosis, treatment and exclusion of clinically important arrhythmias. METHODS AND ANALYSES: This is a UK open prospective parallel group multicentre randomised controlled trial of an immediate 14-day ambulatory patch heart monitor vs standard care in 2234 patients presenting acutely with unexplained syncope. Our patient focused primary endpoint will be number of episodes of syncope at 1 year. Health economic evaluation will estimate the incremental cost per syncope episode avoided and quality-adjusted life year gained. ETHICS AND DISSEMINATION: Informed consent for participation will be sought. The ASPIRED trial received a favourable ethical opinion from South East Scotland Research Ethics Committee 01 (21/SS/0073). Results will be disseminated via scientific publication, lay summary and visual abstract. TRIAL REGISTRATION NUMBER: ISRCTN 10278811.

Retinopathy of prematurity screening criteria and workload implications at Tygerberg Children's Hospital, South Africa: A cross-sectional study.

BACKGROUND: Screening guidelines for retinopathy of prematurity (ROP) used in high-income countries are not appropriate for middle- income countries, and screening requirements may vary even between units within one city. OBJECTIVE: To determine optimal ROP screening criteria, and its workload implications, for Tygerberg Children's Hospital (TCH), Cape Town, South Africa. METHODS: This cross-sectional study included premature infants screened for ROP at TCH from 1 January 2009 to 31 December 2014. Logistic regression analysis for prediction and classification was performed. Predictors were birth weight (BW) and gestational age (GA). Endpoints were clinically significant ROP (CSROP) and type 1 ROP (T1ROP). RESULTS: Of 1 104 eligible infants, 33.4% had ROP (CSROP 9.1%, T1ROP 2.5%). All T1ROP infants received laser therapy. The number of screening examinations was inversely correlated with GA and BW. The number needed to screen to identify one infant requiring treatment was 41 (entailing 83 examinations, 4 screening hours, one technician and three doctors). Screening infants with a GA of ≤28 weeks or a BW of <1 000 g would have detected all infants with T1ROP but missed two outliers with CSROP. These outliers would only have been detected with a GA of ≤32 weeks or a BW <1 500 g. CONCLUSIONS: Detection of infants with T1ROP is resource intensive. Larger infants require screening to include a few outliers, but they require fewer examinations than smaller infants. Making local screening criteria narrower on the basis of a limited evidence base may be dangerous. Risk factors for CSROP in larger infants need to be researched.

Towards early detection of retinoblastoma.

Survival rates for retinoblastoma (RB) in a region of South Africa (SA) of only 50% reflect the high frequency of late presentation, the simple reason for which is lack of effective screening. Early detection of suspected RB would significantly reduce this unacceptably high mortality rate. The SA health system has the expertise to manage a child with RB well. The issue at stake is timely referral of the affected child to one of the specialist treatment centres. Until universal screening with digital imaging becomes a reality, the red reflex test should be mandatory at discharge from all neonatal services and at all subsequent routine health supervision visits. Most RBs would then be detected early.

Congenital iris ectropion uveae presenting with glaucoma in infancy.

A healthy 5-month-old boy presented with a sporadic unilateral right-sided sectorial ectropion uveae, anterior insertion of the iris root, increased IOP, and glaucomatous disk changes. The absence of other additional ocular anomalies and the appearance of the angle led to a diagnosis of congenital iris ectropion syndrome. IOPs became refractory to maximal topical therapy, and trabeculotomy surgery was performed. The patient has since been stabilized on topical agents.

Presumed cytomegalovirus retinitis in human immunodeficiency virus type I-infected South African children.

In human immunodeficiency virus-infected children, cytomegalovirus causes retinitis alone, with dissemination, or with immune reconstitution inflammatory syndrome. We describe 6 severely immunosuppressed African children (median age, 6.7 months) with cytomegalovirus disease. Of the 6 children, 5 had clinical features suggesting ocular disease at presentation. The child in whom retinitis was detected through preemptive screening due to systemic disease achieved normal visual outcome.

Tuberculous meningitis-related optic neuritis: recovery of vision with thalidomide in 4 consecutive cases.

Blindness is an uncommon but devastating complication of tuberculosis meningitis. The main causes are chronically raised intracranial pressure (hydrocephalus and/or tuberculomas) or direct involvement of the optic chiasm or optic nerves by the basal arachnoiditis (inflammation and/or compression). Antituberculosis therapy combined with corticosteroids and control of intracranial pressure constitutes the mainstay of therapy for tuberculous meningitis. Despite these treatment measures, some patients develop blindness, mainly as a result of progressive optochiasmatic arachnoiditis. This led us to explore the role of adjuvant thalidomide therapy, and we describe the dramatic recovery of vision in 4 consecutive cases. Clinical recovery was accompanied by marked radiological improvement on magnetic resonance imaging (MRI) of the brain.

Recovery of vision after adjuvant thalidomide in a child with tuberculous meningitis and acute lymphoblastic leukemia.

A 7-year-old child, on maintenance chemotherapy for acute lymphoblastic leukemia, developed tuberculous meningitis complicated by progressive basal meningeal inflammation and abscess formation, in spite of adequate tuberculosis treatment and adjunctive corticosteriod therapy. The child became blind as a result of involvement of the optic chiasm. After 2 months of adjunctive thalidomide therapy, the child regained vision and cranial magnetic resonance imaging showed marked reduction of the inflammatory changes previously demonstrated. Progression of intracranial tuberculous infection, in spite of a treatment that is generally considered to be adequate, is well recognized. Previous reports of a possible beneficiary role of thalidomide in these cases support an immunological basis. The present case suggests a role for thalidomide in the treatment of blindness due to involvement of the optic chiasm in progressive basal tuberculous meningitis.

Metabolic and functional consequences of cytosolic 5'-nucleotidase-IA overexpression in neonatal rat cardiomyocytes.

Adenosine exerts a spectrum of energy-preserving actions on the heart negative chronotropic effects. The pathways leading to adenosine formation have remained controversial. In particular, although cytosolic 5'-nucleotidases can catalyze adenosine formation in cardiomyocytes, their contribution to the actions of adenosine has not been documented previously. We recently cloned two closely related AMP-preferring cytosolic 5'-nucleotidases (cN-IA and -IB); the A form predominates in the heart. In this study, we overexpressed pigeon cN-IA in neonatal rat cardiomyocytes using an adenovirus. cN-IA overexpression increased adenosine formation and release into the medium caused by simulated hypoxia and by isoproterenol in the absence and presence of inhibitors of adenosine metabolism. Adenosine release was not affected by an ecto-5'-nucleotidase inhibitor, alpha,beta-methylene-ADP, but was affected by a nucleoside transporter, dipyridamole. The positive chronotropic effect of isoproterenol (130 +/-3 vs. 100 +/-4 beats/min) was inhibited (107 +/-3 vs. 94 +/-3 beats/min) in cells overexpressing cN-IA, and this was reversed by the addition of the adenosine receptor antagonist 8-(p-sulfophenyl)theophilline (120 +/- 3 vs. 90 +/- 4 beats/min). Our results demonstrate that overexpressed cN-IA can be sufficiently active in cardiomyocytes to generate physiologically effective concentrations of adenosine at its receptors.