Surgical factors associated with new-onset postoperative atrial fibrillation after lung resection: the EPAFT multicentre study.

PURPOSE OF THE STUDY: Postoperative atrial fibrillation (POAF) is a recognised complication in approximately 10% of major lung resections. In order to best target preoperative treatment, this study aimed at determining the association of incidence of POAF in patients undergoing lung resection to surgical and anatomical factors, such as surgical approach, extent of resection and laterality. STUDY DESIGN: Evaluation of Post-operative Atrial Fibrillation in Thoracic surgery (EPAFT): a multicentre, population-based, retrospective, cross-sectional, observational study including 1367 patients undergoing lung resections between April 2016 and March 2017. The primary outcome was the presence of POAF following resection. POAF was defined as at least one episode of symptomatic or asymptomatic AF confirmed by ECG within 7 days from the thoracic procedure or prior to discharge from the hospital. RESULTS: POAF was observed in 7.4% of patients: 3.1% in minor resection (video-assisted thoracoscopic surgery (VATS): 2.5%; thoracotomy: 3.8%), 9.0% in simple lobectomy (VATS: 7.3%, thoracotomy: 9.9%), 6.0% in complex resection (thoracotomy: 6.3%) and 11.4% in pneumonectomy. POAF was higher in left (4.0%) vs right (2.4%) minor resections, and in left (9.9%) vs right (8.3%) lobectomy, but higher in right (7.5%) complex resections, and the highest in right pneumonectomy (17.6%). No significant variations were observed as per sex, laterality or resected lobes. A positive univariable and multivariable association was observed for increasing age and increasing extent of resection, but not thoracotomy. Median (Q1-Q3) hospital stay was 9 (7-14) days in POAF and 5 (4-7) days in non-AF patients (p<0.001), with an increased cerebrovascular accident burden (p<0.001) and long-term mortality (p<0.001). CONCLUSIONS: Among patients undergoing lung resection, POAF was significantly associated with age, increasing invasiveness of approach and increasing extent of resection. In addition, POAF carried a significant long-term mortality rate and burden of cerebrovascular accident. Appropriate prophylaxis should be targeted at these groups.

Antimicrobial prophylaxis in adult cardiac surgery in the United Kingdom and Republic of Ireland.

BACKGROUND: Deep sternal wound infections are a financially costly complication of cardiac surgery with serious implications for patient morbidity and mortality. Prophylactic antimicrobials have been shown to reduce the incidence of infection significantly. In 2018, the European Association for CardioThoracic Surgery (EACTS) provided clear guidance advising that third-generation cephalosporins are the first-line prophylactic antimicrobial of choice for cardiac surgery via median sternotomy as a result of their broad spectrum of activity and association with reduced postoperative mortality. Despite this guidance, it was believed that UK practice differed from this as a consequence of national concerns surrounding cephalosporins use and Clostridioides difficile infection. METHODS: A survey was developed and distributed to all UK and Republic of Ireland (ROI) cardiac surgery centres in January 2019 to quantify this variation. RESULTS: Of the 38 centres, 34 responded. Variation existed between the antimicrobial agent used, as well as the dosage, frequency and duration of suggested regimens even among centres using the same antimicrobial agent. The most common antimicrobial prophylaxis prescribed was a combination of flucloxacillin and gentamicin (16, 47%). Followed by cefuroxime (6, 17.6%) and cefuroxime combined with a glycopeptide (4, 11.7%). In patients colonised with methicillin-resistant Staphylococcus aureus or those with penicillin allergy gentamicin combined with teicoplanin was most common (42% and 50%, respectively). DISCUSSION: This variation in antimicrobial agents and regimens may well contribute to the varying incidence of surgical site infection seen across the UK and ROI.

Evaluation of Disease Lesions in the Developing Canine MPS IIIA Brain.

Mucopolysaccharidosis IIIA (MPS IIIA) is an inherited neurodegenerative disease of childhood that results in early death. Post-mortem studies have been carried out on human MPS IIIA brain, but little is known about early disease development. Here, we utilised the Huntaway dog model of MPS IIIA to evaluate disease lesion development from 2 to 24 weeks of age. A significant elevation in primarily stored heparan sulphate was observed in all brain regions assessed in MPS IIIA pups ≤9.5 weeks of age. There was a significant elevation in secondarily stored ganglioside (GM3 36:1) in ≤9.5-week-old MPS IIIA pup cerebellum, and other brain regions also exhibited accumulation of this lipid with time. The number of neural stem cells and neuronal precursor cells was essentially unchanged in MPS IIIA dog brain (c.f. unaffected) over the time course assessed, a finding corroborated by neuron cell counts. We observed early neuroinflammatory changes in young MPS IIIA pup brain, with significantly increased numbers of activated microglia recorded in all but one brain region in MPS IIIA pups ≤9.5 weeks of age (c.f. age-matched unaffected pups). In conclusion, infant-paediatric-stage MPS IIIA canine brain exhibits substantial and progressive primary and secondary substrate accumulation, coupled with early and robust microgliosis. Whilst early initiation of treatment is likely to be required to maintain optimal neurological function, the brain's neurodevelopmental potential appears largely unaffected by the disease process; further investigations confirming this are warranted.

Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA.

Intra-cerebrospinal fluid (CSF) injection of recombinant human lysosomal enzyme is a potential treatment strategy for several neurodegenerative lysosomal storage disorders including Sanfilippo syndrome (Mucopolysaccharidosis type IIIA; MPS IIIA). Here we have utilised the MPS IIIA Huntaway dog model to compare the effectiveness of the repeated intermittent bolus injection strategy being used in the trials with an alternate approach; slow, continual infusion of replacement enzyme (recombinant human sulphamidase; rhSGSH) into the spinal CSF using a SynchroMed II® pump attached to a spinal infusion cannula. The ability of each enzyme delivery strategy to ameliorate lesions in MPS IIIA brain was determined in animals treated from ∼three- to six-months of age. Controls received buffer or no treatment. Significant reductions in heparan sulphate (primary substrate) were observed in brain samples from dogs treated via either cisternal or lumbar spinal CSF bolus injection methods and also in slow intra-spinal CSF infusion-treated dogs. The extent of the reduction differed regionally. Pump-delivered rhSGSH was less effective in reducing secondary substrate (GM3 ganglioside) in deeper aspects of cerebral cortex, and although near-amelioration of microglial activation was seen in superficial (but not deep) layers of cerebral cortex in both bolus enzyme-treated groups, pump-infusion of rhSGSH had little impact on microgliosis. While continual low-dose infusion of rhSGSH into MPS IIIA dog CSF reduces disease-based lesions in brain, it was not as efficacious as repeated cisternal or spinal CSF bolus infusion of rhSGSH over the time-frame of these experiments.

Delivery of therapeutic protein for prevention of neurodegenerative changes: comparison of different CSF-delivery methods.

Injection of lysosomal enzyme into cisternal or ventricular cerebrospinal fluid (CSF) has been carried out in 11 lysosomal storage disorder models, with each study demonstrating reductions in primary substrate and secondary neuropathological changes, and several reports of improved neurological function. Whilst acute studies in mucopolysaccharidosis (MPS) type II mice revealed that intrathecally-delivered enzyme (into thoraco-lumbar CSF) accesses the brain, the impact of longer-term treatment of affected subjects via this route is unknown. This approach is presently being utilized to treat children with MPS types I, II and III. Our aim was to determine the efficacy of repeated intrathecal injection of recombinant human sulfamidase (rhSGSH) on pathological changes in the MPS IIIA dog brain. The outcomes were compared with those in dogs treated via intra-cisternal or ventricular routes. Control dogs received buffer or no treatment. Significant reductions in primary/secondary substrate levels in brain were observed in dogs treated via all routes, although the extent of the reduction differed regionally. Treatment via all CSF access points resulted in large reductions in microgliosis in superficial cerebral cortex, but only ventricular injection enabled amelioration in deep cerebral cortex. Formation of glutamic acid decarboxylase-positive axonal spheroids in deep cerebellar nuclei was prevented by treatment delivered via any route. Anti-rhSGSH antibodies in the sera of some dogs did not reduce therapeutic efficacy. Our data indicates the capacity of intra-spinal CSF-injected rhSGSH to circulate within CSF-filled spaces, penetrate into brain and mediate a significant reduction in substrate accumulation and secondary pathology in the MPS IIIA dog brain.