A retrospective cohort study of bacterial native vertebral osteomyelitis and its management in the UK

Background: Bacterial native vertebral osteomyelitis (NVO) can present diagnostic and therapeutic challenges leading to high levels of morbidity and mortality. To inform strategies aimed at improving outcomes in these patients, data are needed on the current aetiology, diagnostic interventions, management and risk factors for treatment failure. Methods: This was a retrospective, multicentre, observational cohort study of adult patients with bacterial NVO across the UK between 1st January 2015 and 31st December 2016. Infectious Disease Society of America (IDSA) guideline standards were selected and used to audit practice relating to the management of these patients. Results: A total of 286 patients were included from 40 hospitals. An organism was identified in 61% of cases by blood culture or biopsy. Of these, 51% were due to Staphylococcus aureus and 12% were due to Gram-negative bacteria. When performed, biopsy obtained a microbiological diagnosis in 50% of cases. Nearly 10% of patients required admission to an Intensive Care Unit, 20% were re-admitted to hospital, 56% experienced complications and 6% died within 90 days. Higher Charlson comorbidity index (CCI) was significantly associated with treatment failure at one month (p = 0.004). Conclusions: This study identified opportunities to improve UK practice in the investigation and management of bacterial NVO. The range of organisms isolated supports the use of diagnostic biopsy where blood cultures are non-diagnostic, to guide antimicrobial therapy and strive to avoid treatment failure or complications. This study shows a clear need for antibiotic guidelines to reflect the current aetiology of NVO and authors support the creation of a formal registry

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection

Objective: To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes. Methods: SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221). Results: SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable. Conclusion: While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients

Pregnancy and Spontaneous Coronary Artery Dissection : Lessons From Survivors and Nonsurvivors

n/aFunding Agencies|British Heart Foundation [PG/13/96/30608]; National Institute for Health and Care Research rare disease translational collaboration; Leicester National Institute for Health and Care Research Biomedical Research Center; Beat SCAD</p

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear. To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls. This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA. Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year). The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index). Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events. In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare

Spontaneous Coronary Artery Dissection: Insights on Rare Genetic Variation from Genome Sequencing

Background - Spontaneous coronary artery dissection (SCAD) occurs when an epicardial coronary artery is narrowed or occluded by an intramural hematoma. SCAD mainly affects women and is associated with pregnancy and systemic arteriopathies, particularly fibromuscular dysplasia. Variants in several genes, such as those causing connective tissue disorders, have been implicated; however, the genetic architecture is poorly understood. Here, we aim to better understand the diagnostic yield of rare variant genetic testing among a cohort of SCAD survivors and to identify genes or gene-sets that have a significant enrichment of rare variants.Methods - We sequenced a cohort of 384 SCAD survivors from the UK, alongside 13,722 UK Biobank controls and a validation cohort of 92 SCAD survivors. We performed a research diagnostic screen for pathogenic variants, and exome-wide and gene-set rare variant collapsing analyses.Results - The majority of patients within both cohorts are female, 29% of the study cohort and 14% validation cohort have a remote arteriopathy. Four cases across the two cohorts had a diagnosed connective tissue disorder. We identified pathogenic or likely pathogenic variants in seven genes (PKD1, COL3A1, SMAD3, TGFB2, LOX, MYLK, and YY1AP1) in 14/384 cases in the study cohort and in 1/92 cases in the validation cohort. In our rare variant collapsing analysis, PKD1 was the highest ranked gene and several functionally plausible genes were enriched for rare variants, although no gene achieved study-wide statistical significance. Gene-set enrichment analysis suggested a role for additional genes involved in renal function.Conclusions - By studying the largest sequenced cohort of SCAD survivors we demonstrate that, based on current knowledge, only a small proportion have a pathogenic variant that could explain their disease. Our findings strengthen the overlap between SCAD and renal and connective tissue disorders and we highlight several new genes for future validation.</div

Evaluating current acute aortic syndrome pathways: Collaborative Acute Aortic Syndrome Project (CAASP)

Acknowledgements: J.Z. and A.A.S. share joint authorship. S.N. and G.V share joint senior authorship. We would like to thank The Aortic Disease Charitable Trust for their support of this work.Abstract Background Diagnosis of acute aortic syndrome is challenging and associated with high perihospital mortality rates. The study aim was to evaluate current pathways and understand the chronology of acute aortic syndrome patient care. Method Consecutive patients with acute aortic syndrome imaging diagnosis between 1 January 2018 and 1 June 2021 were identified using a predetermined search strategy and followed up for 6 months through retrospective case note review. The UK National Interventional Radiology Trainee Research and Vascular and Endovascular Research Network co-ordinated the study. Results From 15 UK sites, 620 patients were enrolled. The median age was 67 (range 25–98) years, 62.0% were male and 92.9% Caucasian. Type-A dissection (41.8%) was most common, followed by type-B (34.5%); 41.2% had complicated acute aortic syndrome. Mode of presentation included emergency ambulance (80.2%), self-presentation (16.2%), and primary care referral (3.6%). Time (median (i.q.r.)) to hospital presentation was 3.1 (1.8–8.6) h and decreased by sudden onset chest pain but increased with migratory pain or hypertension. Time from hospital presentation to imaging diagnosis was 3.2 (1.3–6.5) h and increased by family history of aortic disease and decreased by concurrent ischaemic limb. Time from diagnosis to treatment was 2 (1.0–4.3) h with interhospital transfer causing delay. Management included conservative (60.2%), open surgery (32.2%), endovascular (4.8%), hybrid (1.4%) and palliative (1.4%). Factors associated with a higher mortality rate at 30 days and 6 months were acute aortic syndrome type, complicated disease, no critical care admission and age more than 70 years (P &amp;lt; 0.05). Conclusions This study presents a longitudinal data set linking time-based delays to diagnosis and treatment with clinical outcomes. It can be used to prioritize research strategies to streamline patient care. </jats:sec