Longitudinal reduction in fluoroscopy with continued use of 3-dimensional electroanatomic mapping systems in catheter ablation of supraventricular tachycardia - then and now.

BACKGROUND: Catheter ablation is a first-line treatment for symptomatic, recurrent supraventricular tachycardia (SVT). This study aims to demonstrate if 3D-electroanatomic mapping (EAM) during SVT ablation reduces fluoroscopy time (FT) and determine if further reductions in FT are observed longitudinally. METHODS: All cases of SVT ablation between May 2011-May 2022 at a single tertiary centre were prospectively recruited. FT between the cohorts with and without EAM were compared. Within the EAM subset, the trend of FT across the years was analysed. RESULTS: There were 1758 cases included, 563 without EAM, 1195 with EAM. EAM was associated with a longer procedure time (mean + 8.8 min, p = 0.001), but with mean reductions in FT and dose area product (DAP) by 19.6 min and 18 621 mGy*cm2 respectively (p < 0.001). There was comparable efficacy without any increase in complication rates. Over time (2011-2022), further reduction in FT of 0.9 min year on year was observed (p = 0.001). Between 2011 and 2017, there was a significant reduction in FT of 1.1 min year on year (p = 0.019), which was not observed from 2017 onwards (p = 0.061). The greatest reduction in FT was after the first year of adoption. CONCLUSION: EAM in SVT ablation reduces fluoroscopy use. FT was initially observed to reduce further over time before plateauing, likely due to increased operator experience. While there is increased interest in zero fluoroscopy SVT ablation, complementary use of fluoroscopy may still be necessary in complex cases.

Cytomegalovirus-associated pseudomembranous colitis in a kidney transplant recipient.

Pseudomembranous colitis (PMC) is classically associated with Clostridium difficile infection. We report a rare case of cytomegalovirus (CMV)-associated PMC in a 52-year-old female patient who had undergone kidney transplantation more than 20 years ago and was on low dose prednisolone and ciclosporin. She presented with an acute history of fever, lethargy, vomiting and diarrhoea on admission. Computed tomography of the abdomen showed extensive colitis, and colonoscopy revealed extensive pseudomembrane formation. Multiple tests for Clostridium difficile and other common microbiological causes of colitis were negative. CMV DNAemia and colonic biopsies confirmed the diagnosis of CMV colitis. The patient responded to prompt CMV treatment, as demonstrated by clinical, endoscopic, and histological response. While CMV is a common pathogen in the solid organ transplant population that is familiar to most transplant physicians, it may present atypically as PMC. Here, we review the literature on CMV-associated PMC and its relevance to solid organ transplant recipients. To our knowledge, this is the first reported case of CMV-associated PMC in a kidney transplant recipient.

The influence of smoking on the pattern of disability and relapse risk in AQP4-positive Neuromyelitis Optica Spectrum Disorder, MOG-Ab Disease and Multiple Sclerosis.

BACKGROUND: the role of smoking on clinical outcomes of central nervous system (CNS) inflammatory disorders is unclear. To assess the effect of smoking on relapses and disability in neuromyelitis optica with aquaporin-4-antibodies (NMOSD-AQP4-Ab), Myelin Oligodendrocyte Glycoprotein-antibodies associated disease (MOGAD) and relapsing remitting Multiple Sclerosis (MS) patients. METHODS: in a UK cohort of 101 NMOSD-AQP4-Ab, 70 MOGAD and 159 MS, and a Korean cohort of 97 NMOSD-AQ4-Ab, time to first relapse, annualised relapse rate, onset relapse severity and recovery, time to Expanded Disability Status Score(EDSS)/secondary progressive MS (SPMS) were compared between never-smokers and ever-smokers. All clinical data were collected under the local ethics between January 2017 and January 2019. RESULTS: Smoking did not affect the risk of relapse in any of the diseases. The risk of reaching EDSS 6.0 in the UK NMOSD-AQP4-Ab cohort was higher in ever smokers but this did not achieve significance (HR 2.12, p=0.068). When combining the UK and Korea NMOSD-AQP4-Ab cohorts, poorer recovery from the onset attack was significantly more frequent in the ever-smokers versus the never smokers (55% vs 38%, p=0.04). In the MS cohort the risk of reaching EDSS 6 and SPMS was significantly higher in the ever-smokers (HR=2.67, p=0.01 and HR=3.18, p=0.001). In MOGAD similar patterns were seen without reaching significance. CONCLUSIONS: In NMOSD-AQP4-Ab smoking associates with worse disability not through an increased risk of relapses but through poor relapse recovery. As in MS, smoking cessation should be encouraged in NMOSD-AQP4-Ab.

Maternal Allopurinol Prevents Cardiac Dysfunction in Adult Male Offspring Programmed by Chronic Hypoxia During Pregnancy.

Integrating functional and molecular levels, we investigated the effects of maternal treatment with a xanthine oxidase inhibitor on the programming of cardiac dysfunction in adult offspring using an established rat model of hypoxic pregnancy. Female Wistar rats were divided into normoxic or hypoxic (13% O2) pregnancy±maternal allopurinol treatment (30 mg kg-1 d-1). At 4 months, hearts were isolated from 1 male per litter per outcome variable to determine cardiac function and responses to ischemia-reperfusion in a Langendorff preparation. Sympathetic dominance, perfusate CK (creatine kinase) and LDH (lactate dehydrogenase) and the cardiac protein expression of the ß1-adrenergic receptor, the M2 Ach receptor (muscarinic type-2 acetylcholine receptor), and the SERCA2a (sarcoplasmic reticulum Ca2+ ATPase 2a) were determined. Relative to controls, offspring from hypoxic pregnancy showed elevated left ventricular end diastolic pressure (+34.7%), enhanced contractility (dP/dtmax, +41.6%), reduced coronary flow rate (-21%) and an impaired recovery to ischemia-reperfusion (left ventricular diastolic pressure, area under the curve recovery -19.1%; all P<0.05). Increased sympathetic reactivity (heart rate, +755.5%; left ventricular diastolic pressure, +418.9%) contributed to the enhanced myocardial contractility ( P<0.05). Perfusate CK (+431%) and LDH (+251.3%) and the cardiac expression of SERCA2a (+71.4%) were also elevated ( P<0.05), further linking molecular markers of cardiac stress and injury to dysfunction. Maternal allopurinol restored all functional and molecular indices of cardiac pathology. The data support a link between xanthine oxidase-derived oxidative stress in hypoxic pregnancy and cardiac dysfunction in the adult offspring, providing a target for early intervention in the developmental programming of heart disease.

Hepitopes: A live interactive database of HLA class I epitopes in hepatitis B virus.

Increased clinical and scientific scrutiny is being applied to hepatitis B virus (HBV), with focus on the development of new therapeutic approaches, ultimately aiming for cure. Defining the optimum natural CD8+ T cell immune responses that arise in HBV, mediated by HLA class I epitope presentation, may help to inform novel immunotherapeutic strategies. Therefore, we have set out to develop a comprehensive database of these epitopes in HBV, coined 'Hepitopes'. This undertaking has its foundations in a systematic literature review to identify the sites and sequences of all published class I epitopes in HBV. We also collected information regarding the methods used to define each epitope, and any reported associations between an immune response to this epitope and disease outcome. The results of this search have been collated into a new open-access interactive database that is available at http://www.expmedndm.ox.ac.uk/hepitopes. Over time, we will continue to refine and update this resource, as well as inviting contributions from others in the field to support its development. This unique new database is an important foundation for ongoing investigations into the nature and impact of the CD8+ T cell response to HBV.