Publications by authors named "Nelson Wang"

39 Publications

Atypical Lemierre's syndrome complicated by transcalvarial brain herniation.

J Paediatr Child Health 2021 Feb 18. Epub 2021 Feb 18.

Department of General Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/jpc.15366DOI Listing
February 2021

Can fosfomycin be used for the treatment of Gram-negative urinary tract infections in children?

Arch Dis Child 2021 Jan 18. Epub 2021 Jan 18.

Infectious Diseases Unit, Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.

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http://dx.doi.org/10.1136/archdischild-2020-320529DOI Listing
January 2021

COVID-19: getting to the heart of the matter.

Eur J Heart Fail 2020 12 5;22(12):2216-2218. Epub 2020 Oct 5.

School of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

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http://dx.doi.org/10.1002/ejhf.2007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537077PMC
December 2020

Rat-bite fever in a child without a bite.

Arch Dis Child 2020 Aug 20. Epub 2020 Aug 20.

Department of Infection and Immunity, Monash Children's Hospital, Clayton, Victoria, Australia.

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http://dx.doi.org/10.1136/archdischild-2020-320327DOI Listing
August 2020

Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.

Glycobiology 2020 Aug 8. Epub 2020 Aug 8.

Department of Biosciences, Section for Section for Genetics and Evolutionary Biology, Centre for Integrative Microbial Evolution, University of Oslo, 0371 Oslo, Norway.

Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease. Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including non-pathogenic species. However, there are inconsistencies between pgl gene status and observed glycan structures. One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp. glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide. Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds. Moreover, PglG function in N. elongata subsp. glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis. We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp. glycolytica. The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species. Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes. Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
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http://dx.doi.org/10.1093/glycob/cwaa073DOI Listing
August 2020

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

JAMA Cardiol 2020 11;5(11):1219-1226

The George Institute for Global Health, The University of New South Wales, Sydney, Australia.

Importance: Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia.

Objective: To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care.

Design, Setting, And Participants: A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019.

Interventions: Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care.

Main Outcomes And Measures: Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression.

Results: Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared with the usual care group at baseline (predicted mean [SD] increase in regimen potency: triple pill, 15 [6] mm Hg; usual care, 10 [5] mm Hg; P < .001), whereas there were no significant differences at the week 6 or at week 12 visit. Clinic systolic BP level was the only consistent predictor of treatment intensification during follow-up. During follow-up, there were 23 vs 54 unique treatment regimens per 100 treated patients in the triple pill vs usual care groups, respectively (P < .001).

Conclusions And Relevance: Triple pill FDC therapy was associated with greater rates of therapeutic inertia compared with usual care. Despite this, triple pill FDC therapy substantially simplified prescribing patterns and improved 6-month BP control rates compared with usual care. Further improvements in hypertension control could be achieved by addressing therapeutic inertia among the minority of patients who do not achieve BP control after initial FDC therapy.

Trial Registration: ANZCTR Identifier: ACTRN12612001120864.
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http://dx.doi.org/10.1001/jamacardio.2020.2739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376473PMC
November 2020

Regression to the mean in home blood pressure: Analyses of the BP GUIDE study.

J Clin Hypertens (Greenwich) 2020 Jul 7;22(7):1184-1191. Epub 2020 Jul 7.

The George Institute for Global Health Australia, UNSW Sydney, Sydney, NSW, Australia.

The aim of our study was to estimate the size of regression to the mean with home blood pressure (BP) monitoring and compare with that for office BP. Office and home BP measures were obtained from the BP GUIDE (value of central Blood Pressure for GUIDing managEment for hypertension) study, in which 286 patients had BP measured every 3 months for 12 months. Patients were categorized by 10 mm Hg strata of baseline BP, and regression to the mean measures was calculated for home and office BP. High baseline home BP readings tended to be lower on long-term follow-up, and low baseline readings tended to be higher. For example, patients in the group with mean baseline home systolic BP ≥ 150 mm Hg had a mean baseline systolic BP of 156 mm Hg, which fell to 143 mm Hg at 12 months; and patients in the group with mean baseline home systolic BP < 120 mm Hg had a mean baseline systolic BP of 113 mm Hg which rose to 120 mm Hg at 12 months. Similar patterns were seen in intervention and control groups, and for diastolic BP. The regression dilution ratio for home systolic BP and diastolic BP was 0.52 and 0.64, respectively, compared to 0.40 and 0.55 for office systolic BP and diastolic BP, respectively. Home BP is subject to regression to the mean to a similar degree as office BP. These findings have implications for the diagnosis and management of hypertension using home BP.
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http://dx.doi.org/10.1111/jch.13933DOI Listing
July 2020

Prevalence and seasonal variation of precipitants of heart failure hospitalization and risk of readmission.

Int J Cardiol 2020 10 29;316:152-160. Epub 2020 Apr 29.

Sydney Medical School, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia. Electronic address:

Aims: To determine the prevalence and seasonal variation in precipitants of heart failure (HF) hospitalization and the risk of subsequent HF hospitalizations.

Methods: We analysed the characteristics and outcomes of patients hospitalized with HF and enrolled in the Management of Cardiac Failure program in Sydney, Australia. Potential precipitants of HF hospitalization were identified, and Cox-regression analyses performed according to the precipitant.

Results: Among 6918 patients hospitalized with HF, 5384 (78%) had identified one or more precipitating factors leading to the hospitalization and 3648 (53%) had a single identifiable precipitant. Most precipitants were due to one or more of five prespecified causes - infection (n = 2014), ischemia (n = 1781), arrhythmia (n = 1724), medication related (n = 925) and diet non-compliance (n = 408). All precipitants were more common during winter (p < 0.001), especially infection related precipitants, of which 36% occurred during winter. Among patients with a single identifiable precipitant, one-year risk for HF readmission was lower when the precipitant was arrhythmia (16%) or infection (17%) than when the precipitant was ischemia (21%), dietary non-compliance (23%) or medication related (25%). The precipitant for HF rehospitalizations were more likely to be the same precipitant for the initial admission: infection vs no infection (HR 1.51, 95% CI 1.08-2.13), ischemia vs no ischemia (HR 2.79, 95% CI 1.83-4.25), arrhythmia vs no arrhythmia (HR 3.31, 95% CI 1.87-5.88) and medication related vs not medication related (HR 2.28, 95% CI 1.39-3.74).

Conclusion: The precipitant of HF hospitalization influences the risk and precipitant of subsequent HF hospitalizations. Identifying and targeting interventions towards the precipitating factor may be an important strategy to prevent future HF hospitalizations.
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http://dx.doi.org/10.1016/j.ijcard.2020.04.084DOI Listing
October 2020

Cholesterol lowering: to live longer, start younger?

Aging (Albany NY) 2020 02 19;12(4):3119-3120. Epub 2020 Feb 19.

Sydney Medical School, University of Sydney, Sydney, Australia.

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http://dx.doi.org/10.18632/aging.102867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066884PMC
February 2020

Genetic determinants of genus-level glycan diversity in a bacterial protein glycosylation system.

PLoS Genet 2019 12 23;15(12):e1008532. Epub 2019 Dec 23.

Department of Biosciences, Center for Integrative Microbial Evolution, University of Oslo, Oslo, Norway.

The human pathogens N. gonorrhoeae and N. meningitidis display robust intra- and interstrain glycan diversity associated with their O-linked protein glycosylation (pgl) systems. In an effort to better understand the evolution and function of protein glycosylation operating there, we aimed to determine if other human-restricted, Neisseria species similarly glycosylate proteins and if so, to assess the levels of glycoform diversity. Comparative genomics revealed the conservation of a subset of genes minimally required for O-linked protein glycosylation glycan and established those pgl genes as core genome constituents of the genus. In conjunction with mass spectrometric-based glycan phenotyping, we found that extant glycoform repertoires in N. gonorrhoeae, N. meningitidis and the closely related species N. polysaccharea and N. lactamica reflect the functional replacement of a progenitor glycan biosynthetic pathway. This replacement involved loss of pgl gene components of the primordial pathway coincident with the acquisition of two exogenous glycosyltransferase genes. Critical to this discovery was the identification of a ubiquitous but previously unrecognized glycosyltransferase gene (pglP) that has uniquely undergone parallel but independent pseudogenization in N. gonorrhoeae and N. meningitidis. We suggest that the pseudogenization events are driven by processes of compositional epistasis leading to gene decay. Additionally, we documented instances where inter-species recombination influences pgl gene status and creates discordant genetic interactions due ostensibly to the multi-locus nature of pgl gene networks. In summary, these findings provide a novel perspective on the evolution of protein glycosylation systems and identify phylogenetically informative, genetic differences associated with Neisseria species.
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http://dx.doi.org/10.1371/journal.pgen.1008532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959607PMC
December 2019

Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participants.

Lancet Diabetes Endocrinol 2020 01;8(1):36-49

University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Sydney Cardiology, Sydney, NSW, Australia. Electronic address:

Background: The benefits of LDL cholesterol-lowering treatment for the prevention of atherosclerotic cardiovascular disease are well established. However, the extent to which these effects differ by baseline LDL cholesterol, atherosclerotic cardiovascular disease risk, and the presence of comorbidities remains uncertain.

Methods: We did a systematic literature search (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, from inception up to June 15, 2019) for randomised controlled trials of statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors with at least 1000 patient-years of follow-up. Random-effects meta-analysis and meta-regressions were done to assess for risk of major vascular events (a composite of cardiovascular mortality, non-fatal myocardial infarction, non-fatal ischaemic stroke, or coronary revascularisation) per 1 mmol/L (38·7 mg/dL) reduction in LDL cholesterol concentrations.

Findings: 327 037 patients from 52 studies were included in the meta-analysis. Each 1 mmol/L reduction in LDL cholesterol was associated with a 19% relative risk (RR) reduction for major vascular events (RR 0·81 [95% CI 0·78-0·84]; p<0·0001). Similar reductions (per 1 mmol/L reduction in LDL cholesterol) were found in trials with participants with LDL cholesterol 2·60 mmol/L or lower, 2·61-3·40 mmol/L, 3·41-4·10 mmol/L, and more than 4·1 mmol/L (p=0·232 for interaction); and in a subgroup of patients who all had a baseline LDL cholesterol less than 2·07 mmol/L (80 mg/dL; RR 0·83 [95% CI 0·75-0·92]; p=0·001). We found greater RR reductions in patients at lower 10-year atherosclerotic cardiovascular disease risk (change in RR per 10% lower 10-year atherosclerotic cardiovascular disease 0·97 [95% CI 0·95-0·98]; p<0·0001) and in patients at younger age across a mean age of 50-75 years (change in RR per 10 years younger age 0·92 [0·83-0·97]; p=0·015). We found no difference in RR reduction for participants with or without diabetes (p=0·878 for interaction) and chronic kidney disease (p=0·934 for interaction).

Interpretation: For each 1 mmol/L LDL cholesterol lowering, the risk reduction of major vascular events is independent of the starting LDL cholesterol or the presence of diabetes or chronic kidney disease. Patients at lower cardiovascular risk and younger age might have a similar relative reduction in risk with LDL-cholesterol lowering therapies and future studies should investigate the potential benefits of earlier intervention.

Funding: None.
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http://dx.doi.org/10.1016/S2213-8587(19)30388-2DOI Listing
January 2020

Heart Rate During the Post-Discharge Home Visit Predicts Mortality in Patients With Heart Failure.

J Card Fail 2020 03 23;26(3):285-286. Epub 2019 Nov 23.

Sydney Medical School, University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia.

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http://dx.doi.org/10.1016/j.cardfail.2019.11.022DOI Listing
March 2020

15-Year Trends in Patients Hospitalised With Heart Failure and Enrolled in an Australian Heart Failure Management Program.

Heart Lung Circ 2019 Nov 17;28(11):1646-1654. Epub 2018 Oct 17.

University of Sydney, Sydney, NSW, Australia; Cardiology Department, Royal North Shore Hospital, Sydney, NSW, Australia.

Background: Heart failure (HF) is associated with high morbidity and mortality, and is a major contributor to health care costs. Since the area continues to be rapidly evolving, the aim of this study was to examine 15-year trends in demographics, precipitants, symptoms and outcomes of patients hospitalised with HF, and consider the individual and societal implications.

Methods: Data were prospectively collected by Heart Failure nurses from patients enrolled in the Management of Cardiac Function program (MACARF) in Northern Sydney, Australia. Analyses of trends were performed using Mantel-Hanzel tests and one-way analysis of variance. Multivariate Cox proportional hazard models were used to determine changes in readmission and mortality rates.

Results: From 2001 to 2015, 5,588 patients were hospitalised with HF and enrolled in the MACARF program. Over the 15-year period, the average age of enrolled patients increased by a decade (from 74 to 84 years), with an increase in hypertension (52% to 67%), chronic kidney disease (11% to 21%), atrial fibrillation/flutter (29% to 44%), and HF with preserved ejection fraction (24% to 35%) but a decrease in ischaemic heart disease (62% to 47%). Infection and atrial arrhythmias were the two most common precipitants of admission (27% and 18% of patients in 2013-15 respectively), while acute ischaemia became less common, and "unknown" precipitant increased to 35%. While increased exertional dyspnoea and peripheral oedema remained the most common presenting symptoms, weight gain, fatigue and chest pain were less frequently identified. Medication trends included an increase in spironolactone use and a decrease in angiotensin converting enzyme inhibitors. Average length of stay reduced while 1- and 3-year mortality rates improved to 11.3% and 26.6% respectively. In contrast, readmission rates have not improved, with current 30-day and 1-year rates of 9.9% and 42.6%.

Conclusions: Significant temporal changes have occurred in the characteristics and outcome of patients with HF, which pose a challenge and opportunity to improve management. Although length of stay and mortality have improved, unchanged readmission rates highlight the importance of addressing the implications of the changing nature of patients with HF.
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http://dx.doi.org/10.1016/j.hlc.2018.10.010DOI Listing
November 2019

Transcatheter, sutureless and conventional aortic-valve replacement: a network meta-analysis of 16,432 patients.

J Thorac Dis 2019 Jan;11(1):188-199

Faculty of Medicine, University of Sydney, Sydney, Australia.

Background: Minimally invasive surgical techniques pose alternatives to conventional surgery for the treatment of aortic stenosis (AS). We present a Bayesian network analysis comparing Valve Academic Research Consortium-2 clinical outcomes between transcatheter aortic valve implantation (TAVI), sutureless (SL-AVR) and conventional aortic valve replacement (CAVR).

Methods: Electronic searches of databases were conducted and seven two-arm randomized-controlled trials and 25 propensity-score-matched studies comparing clinical outcomes of TAVI, SL-AVR and CAVR for treatment of AS were identified. Bayesian Markov chain Monte Carlo modelling was used to analyze clinical outcomes.

Results: The analysis included 16,432 patients who underwent TAVI [7,056], SL-AVR [1,238] or CAVR [8,138]. Compared to CAVR, TAVI and SL-AVR were associated with reduced postoperative major bleeding of 59% (OR 0.41, 95% CI: 0.28-0.59) and 44% (OR 0.56, 95% CI: 0.30-0.99) respectively. TAVI had a 41% reduction in postoperative myocardial infarction (OR 0.59, 95% CI: 0.40-0.86) and SL-AVR had a 40% reduction in postoperative acute kidney injury (AKI) (OR 0.62, 95% CI: 0.42-0.86). Compared to TAVI, CAVR and SL-AVR had a reduction in moderate/severe paravalvular regurgitation of 89% (OR 0.11, 95% CI: 0.07-0.16) and 92% (OR 0.08, 95% CI: 0.03-0.17). CAVR had a 67% decreased postoperative permanent pacemaker (PPM) implantation compared to TAVI (OR 0.33, 95% CI: 0.24-0.45) and a 63% reduction compared to SL-AVR (OR 0.37, 95% CI: 0.22-0.61). There were no differences in 30-day mortality or postoperative stroke between the groups.

Conclusions: In selected patients, minimally invasive surgical interventions including TAVI and SL-AVR for severe AS are viable alternatives to conventional surgery. However, TAVI is associated with increased paravalvular regurgitation, whereas TAVI and SL-AVR are associated with increased conduction disturbances compared to CAVR.
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http://dx.doi.org/10.21037/jtd.2018.12.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384334PMC
January 2019

Tricuspid regurgitation is associated with increased mortality independent of pulmonary pressures and right heart failure: a systematic review and meta-analysis.

Eur Heart J 2019 02;40(5):476-484

Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.

Aims: To undertake a systematic review and meta-analysis to determine the influence of tricuspid regurgitation (TR) severity on mortality.

Methods And Results: We performed a systematic search for studies reporting clinical outcomes of patients with TR. The primary endpoint was all-cause mortality and secondary endpoints were cardiac mortality and hospitalization for heart failure (HF). Overall risk ratios (RR) and 95% confidence intervals (CIs) were derived for each endpoint according to the severity of TR by meta-analysing the effect estimates of eligible studies. Seventy studies totalling 32 601 patients were included in the analysis, with a mean (±SD) follow-up of 3.2 ± 2.1 years. Moderate/severe TR was associated with a two-fold increased mortality risk compared to no/mild TR (RR 1.95, 95% CI 1.75-2.17). Moderate/severe TR remained associated with higher all-cause mortality among 13 studies which adjusted for systolic pulmonary arterial pressures (RR 1.85, 95% CI 1.44-2.39), and 15 studies, which adjusted for right ventricular (RV) dysfunction (RR 1.78, 95% CI 1.49-2.13). Moderate/severe TR was also associated with increased cardiac mortality (RR 2.56, 95% CI 1.84-3.55) and HF hospitalization (RR 1.73, 95% CI 1.14-2.62). Compared to patients with no TR, patients with mild, moderate, and severe TR had a progressively increased risk of all-cause mortality (RR 1.25, 1.61, and 3.44, respectively; P < 0.001 for trend).

Conclusions: Moderate/severe TR is associated with an increased mortality risk, which appears to be independent of pulmonary pressures and RV dysfunction.
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http://dx.doi.org/10.1093/eurheartj/ehy641DOI Listing
February 2019

Disrupted Synthesis of a Di--acetylated Sugar Perturbs Mature Glycoform Structure and Microheterogeneity in the -Linked Protein Glycosylation System of Neisseria elongata subsp. .

J Bacteriol 2019 01 7;201(1). Epub 2018 Dec 7.

Department of Biological Sciences, Center for Integrative Microbial Evolution, University of Oslo, Oslo, Norway

The genus includes three major species of importance to human health and disease (, , and ) that express broad-spectrum -linked protein glycosylation (Pgl) systems. The potential for related Pgl systems in other species in the genus, however, remains to be determined. Using a strain of subsp. , a unique tetrasaccharide glycoform consisting of di--acetylbacillosamine and glucose as the first two sugars followed by a rare sugar whose mass spectrometric fragmentation profile was most consistent with di--acetyl hexuronic acid and a -acetylhexosamine at the nonreducing end has been identified. Based on established mechanisms for UDP-di--acetyl hexuronic acid biosynthesis found in other microbes, we searched for genes encoding related pathway components in the subsp. genome. Here, we detail the identification of such genes and the ensuing glycosylation phenotypes engendered by their inactivation. While the findings extend the conservative nature of microbial UDP-di--acetyl hexuronic acid biosynthesis, mutant glycosylation phenotypes reveal unique, relaxed specificities of the glycosyltransferases and oligosaccharyltransferases to incorporate pathway intermediate UDP-sugars into mature glycoforms. Broad-spectrum protein glycosylation (Pgl) systems are well recognized in bacteria and archaea. Knowledge of how these systems relate structurally, biochemically, and evolutionarily to one another and to others associated with microbial surface glycoconjugate expression is still incomplete. Here, we detail reverse genetic efforts toward characterization of protein glycosylation mutants of subsp. that define the biosynthesis of a conserved but relatively rare UDP-sugar precursor. The results show both a significant degree of intra- and transkingdom conservation in the utilization of UDP-di--acetyl-glucuronic acid and singular properties related to the relaxed specificities of the subsp. system.
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http://dx.doi.org/10.1128/JB.00522-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287464PMC
January 2019

Direct endovascular thrombectomy and bridging strategies for acute ischemic stroke: a network meta-analysis.

J Neurointerv Surg 2019 May 5;11(5):443-449. Epub 2018 Oct 5.

Faculty of Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.

Objectives: The present Bayesian network meta-analysis aimed to compare the various strategies for acute ischemic stroke: direct endovascular thrombectomy within the thrombolysis window in patients with no contraindications to thrombolysis (DEVT); (2) direct endovascular thrombectomy secondary to contraindications to thrombolysis (DEVTc); (3) endovascular thrombectomy in addition to thrombolysis (IVEVT); and (4) thrombolysis without thrombectomy (IVT).

Methods: Six electronic databases were searched from their dates of inception to May 2017 to identify randomized controlled trials (RCTs) comparing IVT versus IVEVT, and prospective registry studies comparing IVEVT versus DEVT or IVEVT versus DEVTc. Network meta-analyses were performed using ORs and 95% CIs as the summary statistic.

Results: We identified 12 studies (5 RCTs, 7 prospective cohort) with a total of 3161 patients for analysis. There was no significant difference in good functional outcome at 90 days (modified Rankin Scale score ≤2) between DEVT and IVEVT. There was no significant difference in mortality between all treatment groups. DEVT was associated with a 49% reduction in intracranial hemorrhage (ICH) compared with IVEVT (OR 0.51; 95% CI 0.33 to 0.79), due to reduction in rates of asymptomatic ICH (OR 0.47; 95% CI 0.29 to 0.76). Patients treated with DEVT had higher rates of reperfusion compared with IVEVT (OR 1.73; 95% CI 1.04 to 2.94).

Conclusions: To our knowledge, this is the first network meta-analysis to be performed in the era of contemporary mechanical thrombectomy comparing DEVT and DEVTc. Our analysis suggests the addition of thrombolysis prior to thrombectomy for large vessel occlusions may not be associated with improved outcomes.
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http://dx.doi.org/10.1136/neurintsurg-2018-014260DOI Listing
May 2019

Cerebral protection devices in transcatheter aortic valve replacement: a clinical meta-analysis of randomized controlled trials.

J Thorac Dis 2018 Mar;10(3):1927-1935

The Collaborative Research (CORE) Group, Macquarie University, Sydney, Australia.

Background: Neurological complications after undergoing transcatheter aortic valve replacement (TAVR) may be reduced with cerebral protection (CP) devices. However, randomized controlled trials (RCTs) have failed to demonstrate convincing evidence of improvements in hard clinical endpoints in patients with CP. The aim of this study was to compare clinical outcomes of TAVR patients with and without CP devices.

Methods: Electronic searches were performed using four electronic databases from their dates of inception to May 2017. RCTs that reported outcomes for patient cohorts that underwent TAVR procedures with and without CP were included. Crude odds ratios (ORs) and 95% confidence intervals were calculated using random effects model.

Results: A total of five RCTs were included, totalling 643 patients, 386 of whom were randomized to TAVR + CP and 257 with TAVR only. The primary composite endpoint of all-cause mortality and stroke at 30 days was lower in patients undergoing CP devices compared to those patients with TAVR alone (OR, 0.54; 95% CI, 0.30 to 0.98). Use of CP devices was also associated with lower new total lesion volume (standardised mean difference, -0.49; 95% CI, -0.96 to -0.03). There was a non-significant reduction in the risk of secondary clinical endpoints of all-cause mortality, stroke, life-threatening bleed, acute kidney injury and major vascular complications in patients randomized to TAVR + CP.

Conclusions: Use of CP devices in TAVR appears to be safe and may be associated with a reduction in stroke/death.
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http://dx.doi.org/10.21037/jtd.2018.01.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906364PMC
March 2018

Characteristics and outcome for heart failure patients with mid-range ejection fraction.

J Cardiovasc Med (Hagerstown) 2018 Jun;19(6):297-303

Sydney Medical School, University of Sydney.

Aims: The aim of this study was to compare precipitants, presenting symptoms and outcomes of patients with heart failure and mid-range ejection fraction (HFmrEF), heart failure and preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) in an Australian cohort.

Methods: We divided 5236 patients in the Management of Cardiac Failure program in Northern Sydney Australia, into HFmrEF (n = 780, 14.9%), HFpEF (n = 1956, 37.4%) and HFrEF (n = 2500, 47.8%), using a cutoff left ventricular ejection fraction of 40-49, at least 50 and less than 40%, respectively.

Results: For most characteristics, the HFmrEF patients were intermediate. Hypertension among the HFrEF, HFmrEF and HFpEF groups was present in 50.6, 61.7 and 68.9%, respectively; age more than 85 years was present in 35.1, 37.6 and 42.2%; atrial fibrillation in 35.3, 44.2 and 49.9%; and elevated serum creatinine (>100 μmol/l) in 59.2, 55.6 and 51.0%. For ischemic heart disease and ischemia as a precipitant of admission, HFmrEF patients were similar to the HFrEF group, and more common than in HFpEF. Mortality rates were not significantly different between the three groups. Readmission rates were highest for HFpEF (40.2%), followed by HFmrEF (42.4%) and HFrEF (45.4%), largely due to differences in nonheart failure readmission.

Conclusion: Clinically, HFmrEF represents an intermediate phenotype, with the exception of resembling HFrEF with a higher incidence of ischemic heart disease.
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http://dx.doi.org/10.2459/JCM.0000000000000653DOI Listing
June 2018

Effectiveness and safety of simultaneous hybrid thoracoscopic endocardial catheter ablation of atrial fibrillation in obese and non-obese patients.

J Thorac Dis 2017 Sep;9(9):3087-3096

Department of Cardiology, Maastricht University, Maastricht, the Netherlands.

Background: We evaluated the safety and effectiveness of the hybrid thoracoscopic endocardial epicardial ablation technique for the treatment of atrial fibrillation (AF) in obese versus non-obese patients.

Methods: Between January 2010 and January 2015, a cohort of 61 patients were retrospectively identified to undergo ablation of AF as a stand-alone procedure using a thoracoscopic, hybrid epicardial-endocardial technique. All patients underwent continuous 7-day Holter monitoring at 3, 6 months, 1 year and yearly thereafter.

Results: A total of 40% of the obese cohort had persistent or long-standing AF, compared to 54.9% of the non-obese cohort. There were no deaths or conversion to cardiopulmonary bypass required. At 3-year follow-up, 60% of the obese group were in sinus rhythm (SR) with no episode of AF, atrial flutter or atrial tachycardia lasting 30 s off anti-arrhythmic drugs. This was compared to 70.6% in the non-obese group, with no significant difference between the groups (P=0.468). For success rates on anti-arrhythmic drugs, this was 80% in the obese group compared to 86% in the non-obese group at 3-year follow-up (P=0.637). No patient died and no thromboembolic/bleeding events or procedure-related complications occurred during the follow-up.

Conclusions: In a retrospective cohort with approximately half with persistent or long-standing AF, thoracoscopic hybrid epicardial endocardial ablation proved to be equally effective and safe in obese versus non-obese patients. Current preliminary findings require further validation in multi-institutional prospective studies with larger sample sizes.
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http://dx.doi.org/10.21037/jtd.2017.08.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708470PMC
September 2017

Major Abdominal and Perianal Surgery in Crohn's Disease: Long-term Follow-up of Australian Patients With Crohn's Disease.

Dis Colon Rectum 2018 Jan;61(1):67-76

Department of Gastroenterology, Concord Repatriation General Hospital, The University of Sydney, Concord Clinical School, Sydney, New South Wales, Australia.

Background: Most patients with Crohn's disease still require surgery despite significant advances in medical therapy, surveillance, and management strategies.

Objective: The purpose of this study was to assess surgical strategies and outcomes in Crohn's disease, including surgical recurrence and emergency surgery.

Design: This was a multicenter, retrospective review of a prospectively collected database.

Settings: A specialist-referred cohort of patients with Crohn's disease between 1970 and 2009 was studied.

Patients: Included were 972 patients with Crohn's disease who were referred to the Sydney Inflammatory Bowel Disease cohort database.

Main Outcome Measures: Main outcomes of interest were the rates of major abdominal and perianal surgery between decades (1970-1979, 1980-1989, 1990-1999, and 2000-2009), indications for surgery, types of procedure performed, rate of elective and emergency surgery, risk of surgical recurrence, and predictive factors for surgery.

Results: Between 1970 and 2009, the overall risks of surgery within 5, 10, and 15 years of diagnosis were 31.7%, 43.3%, and 48.4%. The median time to first surgery from time of diagnosis was 2 years (range, 0-31 years). A total of 6.7% of patients required emergency surgery within 5 years of diagnosis. In total, 8.8% of patients required emergency surgery within 15 years. The overall risk of surgical recurrence was 35.9%. The risk of major abdominal surgery significantly decreased between 2000 and 2009 when compared with the 1970 to 1979 period (OR = 0.49 (95% CI, 0.34-0.70). However, the rate of perianal surgery significantly increased (OR = 5.76 (95% CI, 2.54-13.06)). The main indications for surgery were enteric stricture or obstruction, perianal disease, and intra-abdominal fistulas/abscess. Of the 972 patients over 4 decades, only 11 patients (1.1%) were diagnosed with colorectal cancer.

Limitations: This was a specialist-referred cohort, not a population-based study.

Conclusions: The rate of major abdominal surgery has decreased, with surgery reserved for more severe and complicated disease. The natural history of patients with more complicated Crohn's disease and severe phenotypes puts them at higher risk of surgical recurrence and emergency surgery. There has been no reduction in emergency surgery rates and there has been an increase in surgical recurrence despite the reduction in surgical rate morbidity. See Video Abstract at http://links.lww.com/DCR/A483.
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http://dx.doi.org/10.1097/DCR.0000000000000975DOI Listing
January 2018

Predictors of Frequent Readmissions in Patients With Heart Failure.

Heart Lung Circ 2019 Feb 14;28(2):277-283. Epub 2017 Nov 14.

University of Sydney University, Sydney, NSW, Australia; Royal North Shore Hospital, Sydney, NSW, Australia.

Background: Patients with heart failure (HF) have a high incidence of hospital readmissions. However risk models that explore predictors of a single readmission may be less useful at identifying the patients with frequent readmissions who contribute to a disproportionately large proportion of morbidity and health care costs.

Methods: A total of 6252 patients enrolled in the Management of Cardiac Failure Program (MACARF) in Northern Sydney Area Hospitals between 1998 and 2015 were randomly divided into derivation and validation cohorts to create and test a risk model for predictors of ≥2 readmissions or death within 1year of initial hospitalisation for HF.

Results: Multivariate predictors of frequent (≥2) readmissions or death were a history of ischaemic heart disease and chronic kidney disease, being unmarried, having anaemia, low serum albumin, elevated creatinine, prolonged hospital stay (>7 days), and not receiving beta blockers on discharge. Event rates increased with a higher risk score (p<0.001) and the prediction was similar in the validation and derivation cohorts (p=0.588). The C-statistic was 0.65.

Conclusions: Our risk score may assist in focussing health care resources and interventions by identifying the subset of HF patients at increased risk for a disproportionately high burden of disease.
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http://dx.doi.org/10.1016/j.hlc.2017.10.024DOI Listing
February 2019

Predictors of successful chronic total occlusion percutaneous coronary interventions: a systematic review and meta-analysis.

Heart 2018 03 6;104(6):517-524. Epub 2017 Oct 6.

University of Sydney, Sydney, New South Wales, Australia.

Objective: The aim of this study was to identify positive and negative predictors of technical and clinical success for percutaneous coronary intervention (PCI) of chronic total occlusions (CTO).

Methods: We conducted a systematic review and meta-analysis of studies published between 2000 and 2016 analysing rates of CTO PCI success with respect to demographic and angiographic characteristics. Crude ORs and 95% CIs for each predictor were calculated using a random effects model. Predictors of technical and clinical success were assessed among 28 demographic and 31 angiographic variables. Clinical success was defined as technical success without major adverse cardiac events.

Results: A total of 61 studies, totalling 69 886 patients were included in this analysis. The major demographic characteristics associated with a 20% or greater reduction in the odds of technical and clinical success were a history of myocardial infarction, PCI, coronary artery bypass grafting, stroke/transient ischaemic attack and peripheral vascular disease. Angiographic factors were generally stronger predictors of reduced technical and clinical success. Those associated with >20% odds reduction included non-left anterior descending CTOs, multivessel disease, presence of bridging collaterals, moderate-to-severe calcification, >45 degree vessel bending, tortuous vessel, blunt stump and ostial lesions. Of these, novel predictors included prior PCI, prior stroke, peripheral vascular disease, presence of multivessel disease and bridging collaterals.

Conclusion: The present study has identified strong negative predictors for clinical success for CTO PCI, which will aid in patient selection for this procedure.
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http://dx.doi.org/10.1136/heartjnl-2017-311986DOI Listing
March 2018

Implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: an updated systematic review and meta-analysis of outcomes and complications.

Ann Cardiothorac Surg 2017 Jul;6(4):298-306

Collaborative Research (CORE) Group, Sydney, Australia.

Background: Since the introduction of the implantable cardioverter-defibrillator (ICD) in patients with hypertrophic cardiomyopathy (HCM), the incidence of sudden cardiac death (SCD) has been significantly reduced. Given its widespread use, it is important to identify the outcomes associated with ICD use in patients with HCM. The present paper is a systematic review and meta-analysis of the rates of appropriate and inappropriate interventions, mortality, and device complications in HCM patients with an ICD.

Methods: We conducted a systematic review and meta-analysis on 27 studies reporting outcomes and complications after ICD implantation in patients with HCM. ICD interventions, device complications, and mortality were extracted for analysis.

Results: A total of 3,797 patients with HCM and ICD implantation were included (mean age, 44.5 years; 63% male), of which 83% of patients had an ICD for primary prevention of SCD. The cardiac mortality was 0.9% (95% CI: 0.7-1.3) per year and non-cardiac mortality was 0.8% (95% CI: 0.6-1.2) per year. Annualized appropriate intervention rate was 4.8% and annualized inappropriate intervention was 4.9%. The annual incidence of lead malfunction, lead displacement and infection was 1.4%, 1.3%, and 1.1%, respectively.

Conclusions: ICD use in patients with HCM produces low rates of cardiac and non-cardiac mortality, and an appropriate intervention rate of 4.8% per year. However, moderate rates of inappropriate intervention and device complications warrant careful patient selection in order to optimize the risk to benefit ratio in this select group of patients.
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http://dx.doi.org/10.21037/acs.2017.07.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602202PMC
July 2017

Effect of Preoperative Anemia on the Outcomes of Anterior Cervical Discectomy and Fusion.

Global Spine J 2017 Aug 16;7(5):441-447. Epub 2017 May 16.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Study Design: Retrospective cohort study.

Objective: Preoperative anemia has been associated with an increased need for blood transfusions and postoperative complications. The effects of anemia on the outcomes of anterior cervical discectomy and fusion (ACDF) have not been explored. The present study aimed to evaluate the association between preoperative anemia and 30-day complications following ACDF surgery.

Methods: Data from the American College of Surgeons National Surgical Quality Improvement Program (2005-2012) was used. Preoperative anemia was defined as hematocrit <39% for males and <36% for females. A bivariate analysis was performed on demographic and perioperative variables. Multivariable logistic regression models were employed, adjusting for patient variables, to identify independent risk factors for complications.

Results: A total of 3500 patients were included of which 444 (12.7%) were anemic patients. Multivariate analysis was used to quantify the predictive power of anemia on key postoperative outcomes, while controlling for the other statistically significant. Preoperative anemia was found to be a statistically significant predictor of any complication (odds ratio [OR] = 1.853; 95% confidence interval [CI] = 1.17-2.934; = .0086), pulmonary complications (OR = 3.269; 95% CI = 1.745-6.126; = .0002), intraoperative blood transfusion (OR = 4.364; 95% CI = 1.48-12.866; = 0.0076), return to operating theatre (OR = 2.655; 95% CI = 1.539-4.582; = .0005), and length of hospital stay more than 5 days (OR = 2.151; 95% CI = 1.499-3.085; < .0001).

Conclusion: Preoperative anemia appears to be a significant predictor of perioperative complications, reoperation, and extended length of hospital stay in patients undergoing elective ACDF. Future studies should explore outcomes of treatment of preoperative anemia prior to surgery to determine the optimal management strategy.
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http://dx.doi.org/10.1177/2192568217699404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544160PMC
August 2017

Flexible band versus rigid ring annuloplasty for tricuspid regurgitation: a systematic review and meta-analysis.

Ann Cardiothorac Surg 2017 May;6(3):194-203

Sydney Medical School, University of Sydney, Sydney, Australia.

Background: Up to 20% of patients have pre-discharge residual moderate to severe tricuspid regurgitation (TR) after tricuspid repair. Reoperations for recurrent TR carry high mortality rates, which emphasizes the importance of identifying the optimal technique for the surgical management of TR. The present study is a systematic review and meta-analysis that aims to compare short and long term survival and freedom from TR of flexible band ring versus rigid ring for annuloplasty of TR.

Methods: We conducted a systematic review and meta-analysis of comparative studies to evaluate these procedures. A systematic search of the literature was performed from six electronic databases. Pooled meta-analysis was conducted using odds ratio (OR) and weighted mean difference (WMD).

Results: The rates of in-hospital mortality were not different between the two groups, with cumulative rates of 6.9% for flexible band and 7.3% for rigid ring (OR: 0.92; 95% CI: 0.49-1.71). Rates of stroke were also similar with 1.7% of flexible band and 1.3% of rigid rings suffering a perioperative stroke (OR: 1.29; 95% CI: 0.74-2.23). Rigid ring had significantly better freedom from grade ≥2 TR at 5 years (OR: 0.44; 95% CI: 0.20-0.99) and overall (P=0.005). There was no significant difference in overall rates of reoperation (P=0.232) and survival (P=0.086) between flexible band and rigid ring.

Conclusions: Both rigid ring and flexible band offer acceptable outcomes for the treatment of TR. Compared to flexible band, rates of TR are stable after rigid ring annuloplasty and long term freedom from TR are superior for rigid ring devices. Large prospective randomized trials are required in order to validate these findings and assess for improvements in patient survival.
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http://dx.doi.org/10.21037/acs.2017.05.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494420PMC
May 2017

Adenosine Testing After Atrial Fibrillation Ablation: Systematic Review and Meta-Analysis.

Heart Lung Circ 2018 May 7;27(5):601-610. Epub 2017 Jun 7.

Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Collaborative Research (CORE) Group, Macquarie University, Sydney, NSW, Australia.

Background: Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). We performed a systematic review and meta-analysis to assess the impact of adenosine administration in patients undergoing PVI for AF.

Methods: Meta-analysis of 22 studies was performed to assess the rates of freedom from AF in 1) patients with dormant PV conduction versus patients without dormant PV conduction, and 2) patients given routine adenosine post PVI versus patients not given adenosine. Relative-risks (RR) were calculated using random effects modelling.

Results: In 18 studies, 3038 patients received adenosine and freedom from AF in those patients with dormant PV reconnection was significantly lower (62.9%) compared to patients without PV reconnection (67.2%) (RR 0.87; 95% CI: 0.78-0.98). In seven studies with 3049 patients, the freedom from AF was significantly higher in patients who received adenosine (67%) versus those patients who did not receive adenosine (63%) (RR: 1.11; 95% CI: 1.01-1.22).

Conclusions: The present study showed clear benefits of adenosine testing for freedom from AF recurrence. Adenosine-guided dormant conduction is associated with higher AF recurrence despite further ablation. Future studies should investigate the optimal methodology, including dosage and waiting time between PVI and adenosine administration.
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http://dx.doi.org/10.1016/j.hlc.2017.04.020DOI Listing
May 2018

Post-dilation in transcatheter aortic valve replacement: A systematic review and meta-analysis.

J Interv Cardiol 2017 Jun 21;30(3):204-211. Epub 2017 Mar 21.

University of Sydney, Sydney, New South Wales, Australia.

Objectives: The aim of this study was to perform a meta-analysis to compare the outcomes of patients undergoing TAVR with and without balloon post-dilation (PD).

Background: PD is a commonly used technique in TAVR to minimize paravalvular regurgitation (PVR), albeit supported by little evidence.

Methods: Systematic review and meta-analysis of 6 studies comparing 889 patients who had PD compared to 4118 patients without PD.

Results: Patients undergoing PD were more likely male (OR 1.92; 95% CI, 1.41-2.61; P < 0.001) and to have coronary artery disease (OR 1.31; 95% CI, 1.03-1.68; P = 0.03) than those patients not requiring PD. There were no significant differences in 30-day mortality (OR 1.24; 95% CI, 0.88-1.74; P = 0.22) and myocardial infarction (OR 0.93; 95% CI, 0.46-1.90; P = 0.85). Patients undergoing TAVR did not have higher 1-year mortality rates (OR 0.98; 95% CI, 0.61-1.56; P = 0.92). The incidence of stroke was significantly greater in patients with PD (OR, 1.71; 95% CI, 1.10-2.66). PD was able to reduce the incidence of moderate-severe PVR by 15 fold (OR 15.0; 95% CI, 4.2-54.5; P < 0.001), although rates of moderate-severe PVR were still higher after PD than patients who did not require PD (OR 3.64; 95% CI, 1.96-6.75; P < 0.001).

Conclusions: PD significantly improves rates of PVR, however careful patient selection is needed to minimize increased risk of strokes.
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http://dx.doi.org/10.1111/joic.12378DOI Listing
June 2017

Paediatric vertebral artery aneurysms: a literature review.

ANZ J Surg 2017 May 20;87(5):339-344. Epub 2017 Mar 20.

NeuroSpine Surgery Research Group (NSURG), Prince of Wales Private Hospital, Sydney, New South Wales, Australia.

Vertebral artery (VA) aneurysms in the paediatric population are a rare but a serious condition. However, the epidemiology of paediatric VA aneurysms is poorly understood and there is little consensus on what constitutes the appropriate treatment. Although multiple treatment options are available, including surgery, endovascular approaches, coil embolization and parent artery occlusion, there is limited clinical evidence regarding which approach is most optimal. This review outlines the current literature and evidence outlining the epidemiology, presentation, pathogenesis and treatment of paediatric VA aneurysms.
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http://dx.doi.org/10.1111/ans.13940DOI Listing
May 2017

Transcatheter aortic valve implantation (TAVI) versus sutureless aortic valve replacement (SUAVR) for aortic stenosis: a systematic review and meta-analysis of matched studies.

J Thorac Dis 2016 Nov;8(11):3283-3293

Department of Medicine, University of Sydney, Sydney, Australia;; The Collaborative Research (CORE) Group, Macquarie University, Sydney, Australia.

Background: With improving technologies and an increasingly elderly populations, there have been an increasing number of therapeutic options available for patients requiring aortic valve replacement. Recent evidence suggests that transcatheter aortic valve implantation (TAVI) is one suitable option for high risk inoperable patients, as well as high risk operable patients. Sutureless valve technology has also been developed concurrently, with facilitates surgical aortic valve replacement (SUAVR) by allow resection and replacement of the native aortic valve with minimal sutures and prosthesis anchoring required. For patients amenable for both TAVI and SUAVR, the evidence is unclear with regards to the benefits and risks of either approach. The objectives are to compare the perioperative outcomes and intermediate-term survival rates of TAVI and SUAVR in matched or propensity score matched studies.

Methods: A systematic literature search was performed to include all matched or propensity score matched studies comparing SUAVR versus TAVI for severe aortic stenosis. A meta-analysis with odds ratios (OR) and mean differences were performed to compare key outcomes including paravalvular regurgitation and short and intermediate term mortality.

Results: Six studies met our inclusion criteria giving a total of 741 patients in both the SUAVR and TAVI arm of the study. Compared to TAVI, SUAVR had a lower incidence of paravalvular leak (OR =0.06; 95% CI: 0.03-0.12, P<0.01). There was no difference in perioperative mortality, however SUAVR patients had significantly better survival rates at 1 (OR =2.40; 95% CI: 1.40-4.11, P<0.01) and 2 years (OR =4.62; 95% CI: 2.62-8.12, P<0.01).

Conclusions: The present study supports the use of minimally invasive SUAVR as an alternative to TAVI in high risk patients requiring aortic replacement. The presented results require further validation in prospective, randomized controlled studies.
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http://dx.doi.org/10.21037/jtd.2016.11.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179463PMC
November 2016