Point-of-care diagnosis of tissue fibrosis: a review of advances in vibrational spectroscopy with machine learning.

Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources. Vibrational spectroscopy is a novel technique that offers an alternative atraumatic approach, with short scan times, while providing metabolic and morphological data. This review evaluates vibrational spectroscopy for the assessment of fibrosis, with a focus on point-of-care capabilities. OVID Medline, Embase and Cochrane databases were systematically searched using PRISMA guidelines for search terms including vibrational spectroscopy, human tissue and fibrosis. Studies were stratified based on imaging modality and tissue type. Outcomes recorded included tissue type, machine learning technique, metrics for accuracy and author conclusions. Systematic review yielded 420 articles, of which 14 were relevant. Ten of these articles considered mid-infrared spectroscopy, three dealt with Raman spectroscopy and one with near-infrared spectroscopy. The metrics for detecting fibrosis were Pearson correlation coefficients ranging from 0.65-0.98; sensitivity from 76-100%; specificity from 90-99%; area under receiver operator curves from 0.83-0.98; and accuracy of 86-99%. Vibrational spectroscopy identified fibrosis in myeloproliferative neoplasms in bone, cirrhotic and hepatocellular carcinoma in liver, end-stage heart failure in cardiac tissue and following laser ablation for acne in skin. It also identified interstitial fibrosis as a predictor of early renal transplant rejection in renal tissue. Vibrational spectroscopic techniques can therefore accurately identify fibrosis in a range of human tissues. Emerging data show that it can be used to quantify, classify and provide data about the nature of fibrosis with a high degree of accuracy with potential scope for point-of-care use.

Open arch-my way! Branch first continuous perfusion arch repair (BF-CPAR).

We herein describe our technique of "branch first continuous perfusion arch repair (BF-CPAR)" which does away with both cerebral circulatory arrest and the need for deep hypothermia. We use this technique for all aortic surgeries including for type A acute aortic dissections. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01535-2.

Valve-sparing aortic root replacement: Long-term variables significantly associated with mortality and morbidity.

OBJECTIVES: In aortic root surgery, valve-sparing aortic root replacement is an attractive alternative by mitigating the risks inherent to prosthetic valves; however, little is known about the variables that impact its durability. We review our mid- to long-term outcomes after valve-sparing aortic root replacement and describe factors that impact survival and valve reintervention and insufficiency. METHODS: A retrospective review of 284 consecutive patients undergoing valve-sparing aortic root replacement between November 1999 and January 2022 at Austin Health, Melbourne, Australia, was undertaken, with a median follow-up of 6.43 ± 4.83 years, but up to 22.0 years. Freedom from mortality, aortic reintervention, and insufficiency was analyzed using Kaplan-Meier methods, Cox proportional hazard models, and Fine-Gray analysis. RESULTS: The median age of patients at intervention was 60.0 years (interquartile range, 48.0-67.0), of whom 68 (23.9%) had bicuspid aortic valve disease, 27 (9.5%) had Marfan syndrome, 119 (41.9%) had severe aortic root dilation (>50 mm), and 155 had (54.6%) severe aortic insufficiency at the time of intervention. The 30-day mortality was 1.8%, with freedom from mortality of 96.0% (95% CI, 92.6-97.8) at 5 years and 88.2% (95% CI, 81.4-92.6) at 10 years. Freedom from aortic reintervention was 92.2% (95% CI, 87.7-95.2) at 5 years and 79.8% (95% CI, 71.8-85.8) at 10 years. Factors associated with reintervention were concomitant leaflet repair (hazard ratio, 8.13, 95% CI, 1.07-61.7) and bicuspid valvulopathy (hazard ratio, 2.23, 95% CI, 1.07-4.68), with reintervention in the bicuspid aortic valve being more likely due to aortic stenosis and in the tricuspid aortic valve due to aortic insufficiency (chi-square P = .05). The freedom from aortic insufficiency was 89.1% (95% CI, 83.5-92.9), 84.9% (95% CI, 77.8-89.9) at 5 and 10 years, respectively, and 80.7% (95% CI, 71.0-87.4). CONCLUSIONS: Valve-sparing aortic root replacement has excellent long-term outcomes, with low mortality and reintervention rates. Concomitant leaflet repair and bicuspid valve disease are the only long-term factors associated with reintervention.

Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results: Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20-60) and mature fibrosis of 30% (10%-50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%-15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial-least square regression machine learning, this study predicted the percentage of both immature (R 2 = 0.842) and mature (R 2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion: This study demonstrates that a point-of-care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Towards a point-of-care multimodal spectroscopy instrument for the evaluation of human cardiac tissue.

To demonstrate that point-of-care multimodal spectroscopy using Near-Infrared (NIR) and Raman Spectroscopy (RS) can be used to diagnose human heart tissue. We generated 105 spectroscopic scans, which comprised 4 NIR and 3 RS scans per sample to generate a "multimodal spectroscopic scan" (MSS) for each heart, done across 15 patients, 5 each from the dilated cardiomyopathy (DCM), Ischaemic Heart Disease (IHD) and Normal pathologies. Each of the MSS scans was undertaken in 3 s. Data were entered into machine learning (ML) algorithms to assess accuracy of MSS in diagnosing tissue type. The median age was 50 years (IQR 49-52) for IHD, 47 (IQR 45-50) for DCM and 36 (IQR 33-52) for healthy patients (p = 0.35), 60% of which were male. MSS identified key differences in IHD, DCM and normal heart samples in regions typically associated with fibrosis and collagen (NIR wavenumbers: 1433, 1509, 1581, 1689 and 1725 nm; RS wavelengths: 1658, 1450 and 1330 cm-1). In principal component (PC) analyses, these differences explained 99.2% of the variation in 4 PCs for NIR, 81.6% in 10 PCs for Raman, and 99.0% in 26 PCs for multimodal spectroscopic signatures. Using a stack machine learning algorithm with combined NIR and Raman data, our model had a precision of 96.9%, recall of 96.6%, specificity of 98.2% and Area Under Curve (AUC) of 0.989 (Table 1). NIR and Raman modalities alone had similar levels of precision at 94.4% and 89.8% respectively (Table 1). MSS combined with ML showed accuracy of 90% for detecting dilated cardiomyopathy, 100% for ischaemic heart disease and 100% for diagnosing healthy tissue. Multimodal spectroscopic signatures, based on NIR and Raman spectroscopy, could provide cardiac tissue scans in 3-s to aid accurate diagnoses of fibrosis in IHD, DCM and normal hearts. Table 1 Machine learning performance metrics for validation data sets of (a) Near-Infrared (NIR), (b) Raman and (c and d) multimodal data using logistic regression (LR), stochastic gradient descent (SGD) and support vector machines (SVM), with combined "stack" (LR + SGD + SVM) AUC Precision Recall Specificity (a) NIR model  Logistic regression 0.980 0.944 0.933 0.967  SGD 0.550 0.281 0.400 0.700  SVM 0.840 0.806 0.800 0.900  Stack 0.933 0.794 0.800 0.900 (b) Raman model  Logistic regression 0.985 0.940 0.929 0.960  SGD 0.892 0.869 0.857 0.932  SVM 0.992 0.940 0.929 0.960  Stack 0.954 0.869 0.857 0.932 (c) MSS: multimodal (NIR + Raman) to detect DCM vs. IHD vs. normal patients  Logistic regression 0.975 0.841 0.828 0.917  SGD 0.847 0.803 0.793 0.899  SVM 0.971 0.853 0.828 0.917  Stack 0.961 0.853 0.828 0.917 (d) MSS: multimodal (NIR + Raman) to detect pathological vs. normal patients  Logistic regression 0.961 0.969 0.966 0.984  SGD 0.944 0.967 0.966 0.923  SVM 1.000 1.000 1.000 1.000  Stack 1.000 0.944 0.931 0.969 Bold values indicate values obtained from the stack algorithm and used for analyses.

Pre-Glenn aorto-pulmonary collaterals in single-ventricle patients.

BACKGROUND: In single-ventricle patients undergoing staged-bidirectional Glenn, 36-59% have aorto-pulmonary collateral flow, but risk factors and clinical outcomes are unknown. We hypothesise that shunt type and catheter haemodynamics may predict pre-bidirectional Glenn aorto-pulmonary collateral burden, which may predict death/transplantation, pulmonary artery or aorto-pulmonary collateral intervention. METHODS: Retrospective cohort study of patients undergoing a Norwood procedure for single-ventricle anatomy. Covariates included clinical and haemodynamic characteristics up to/including pre-bidirectional Glenn catheterisation and aorto-pulmonary collateral burden at pre-bidirectional Glenn catheterisation. Multivariable models used to evaluate relationships between risk factors and outcomes. RESULTS: From January 2011 to March 2016, 104 patients underwent Norwood intervention. Male sex (odds ratio 3.36, 95% confidence interval 1.17-11.4), age at pre-bidirectional Glenn assessment (2.12, 1.33-3.39 per month), and pulmonary to systemic flow ratio (1.23, 1.08-1.41 per 0.1 unit) were associated with aorto-pulmonary collateral burden. Aorto-pulmonary collateral burden was not associated with death/transplantation (hazard ratio 1.19, 95% confidence interval 0.37-3.85), pulmonary artery (sub-hazard ratio 1.38, 0.32-2.61), or aorto-pulmonary collateral interventions (sub-hazard ratio 1.11, 0.21-5.76). Longer post-Norwood length of stay was associated with greater risk of death/transplantation (hazard ratio 1.22 per week, 95% confidence interval 1.08-1.38), but lower risk of aorto-pulmonary collateral intervention (sub-hazard ratio 0.86 per week, 95% confidence interval 0.75-0.98). Time to pre-bidirectional Glenn catheterisation was associated with lower risk of pulmonary artery (sub-hazard ratio 0.80 per month, 95% confidence interval 0.65-0.98) and aorto-pulmonary collateral intervention (sub-hazard ratio 0.79, 0.63-0.99). Probability of moderate/severe aorto-pulmonary collateral burden increased with left-to-right shunt (22.5% at <1.0, 57.6% at >1.4) and the age at pre-bidirectional Glenn catheterisation (10.6% at <2 months, 56.9% at >5 months). CONCLUSIONS: Aorto-pulmonary collateral burden is common after Norwood procedure and increases as age at bidirectional Glenn increases. As expected, higher pulmonary to systemic flow ratio is a marker for greater aorto-pulmonary collateral burden pre-bi-directional Glenn; aorto-pulmonary collateral burden does not confer risk of death/transplantation or pulmonary artery intervention.

Near-infrared spectroscopy for structural bone assessment.

Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds. A hand-held NIR spectrometer was used to scan bone samples from 20 patients and predict: bone volume fraction (BV/TV); and trabecular (Tb) and cortical (Ct) thickness (Th), porosity (Po), and spacing (Sp). NIRS scans on both the inner (trabecular) surface or outer (cortical) surface accurately identified variations in bone collagen, water, mineral, and fat content, which then accurately predicted bone volume fraction (BV/TV, inner R2 = 0.91, outer R2 = 0.83), thickness (Tb.Th, inner R2 = 0.9, outer R2 = 0.79), and cortical thickness (Ct.Th, inner and outer both R2 = 0.90). NIRS scans also had 100% classification accuracy in grading the quartile of bone thickness and quality. We believe this is a fundamental step forward in creating an instrument capable of intraoperative real-time use.

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer.

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods: Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor's senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results: Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions: The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Mechanistic Target of Rapamycin Inhibition Prevents Coronary Artery Remodeling in a Murine Model of Kawasaki Disease.

OBJECTIVE: Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD. METHOD: We used a murine model of KD (induced by the injection of the Candida albicans water-soluble complex [CAWS]) and analyzed patient samples to evaluate potential antifibrotic therapies for KD. RESULTS: We identified the mechanistic target of rapamycin (mTOR) pathway as a potential therapeutic target in KD. The mTOR inhibitor rapamycin potently inhibited cardiac fibroblast proliferation in vitro, and vascular fibroblasts up-regulated mTOR kinase signaling in vivo in the CAWS mouse model of KD. We evaluated the in vivo efficacy of mTOR inhibition and found that the therapeutic administration of rapamycin reduced vascular fibrosis and intimal hyperplasia of the coronary arteries in CAWS-injected mice. Furthermore, the analysis of cardiac tissue from KD fatalities revealed that vascular fibroblasts localizing with inflamed coronary arteries up-regulate mTOR signaling, confirming that the mTOR pathway is active in human KD. CONCLUSION: Our findings demonstrate that mTOR signaling contributes to coronary artery remodeling in KD, and that targeting this pathway offers a potential therapeutic strategy to prevent or restrict this pathology in high-risk KD patients.

Branch-first Continuous Perfusion Aortic Arch Replacement: Midterm Results.

BACKGROUND: Aortic arch surgery necessitates interruption of perfusion, thus conferring higher morbidity and mortality compared with other aortic surgery. This report describes a branch-first continuous perfusion aortic arch replacement (BF-CPAR) technique that overcomes these shortcomings and describes midterm results with this technique. METHODS: This report represents the corresponding author's 15-year experience with BF-CPAR, which involves preliminary mobilization and branch reconstruction before circulatory arrest by using a modified trifurcation graft. Demographic, procedural, and outcome (mortality, reintervention, morbidity, and stroke) were analyzed with Kaplan-Meier and Cox regression. RESULTS: Over 15 years (July 2005-February 2021), 155 patients underwent BF-CPAR, at a median age of 66.8 years, 106 (68.3%) on an elective basis and 49 (31.6%) on an emergency basis. There were no aortic deaths after the first postoperative year, thereby resulting in a 1- and 10-year freedom from aortic death constant at 95.6% in patients undergoing elective BF-CPAR and 93.3% in patients undergoing emergency BF-CPAR patients, respectively. Freedom from reintervention on the operated segment at 5 and 9 years was 93.2% and 93.2% in patients undergoing elective cases and 97.1% and 91.4% in emergency cases, respectively. The 10-year freedom from any aortic reintervention was 72.8% in elective patients and 29.2% in emergency patients; there were 38 reinterventions, 76.3% (n = 29/38) done for progression of aneurysmal or dissection disease, of which 79.3% (n = 23/29) were completed endovascularly. Freedom from cerebrovascular-related events at 5 and 10 years was 90.3% and 82.6% in patients undergoing elective BF-CPAR and 75.4% for both time points in patients undergoing emergency BF-CPAR, respectively. CONCLUSIONS: BF-CPAR has excellent 10-year results for elective and emergency cases of arch replacement.

Intimal macrophages develop from circulating monocytes during vasculitis.

Objective: Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune-privileged site during vasculitis. Methods: We have addressed this question for Kawasaki disease (KD), which is a type of vasculitis in children that typically involves the coronary arteries. We used confocal microscopy and flow cytometry to characterise the macrophages that populate the coronary artery intima in KD patient samples and in a mouse model of KD, and furthermore, have applied an adoptive transfer system to trace how these intimal macrophages develop. Results: In KD patients, intimal hyperplasia coincided with marked macrophage infiltration of the coronary artery intima. Phenotypic analysis revealed that these 'intimal macrophages' did not express markers of resident cardiac macrophages, such as Lyve-1, and instead, were uniformly positive for the chemokine receptor Ccr2, suggesting a monocytic lineage. In support of this origin, we show that circulating monocytes directly invade the intima via transluminal migration during established disease, coinciding with the activation of endothelial cells lining the coronary arteries. Conclusions: During KD, intimal macrophages develop from circulating monocytes that infiltrate the inflamed coronary artery intima by transluminal migration.

Can We Better Differentiate Type A Dissections: Evaluating the Role of Aortic Ratios.

OBJECTIVES: Type A aortic dissection (ATAAD) is hypothesised as a progression of aneurysmal dilation, but 60% of patients in the International Registry of Acute Aortic Dissection (iRAD) registry had a maximum aortic diameter (MAD)<55 mm. We aim to demonstrate that size ratios and aortic wall stress, assessed using a simplified markers, are unique to aortic patients who have had adverse events (ATAAD) compared to those who have not (thoracic aortic aneurysm [TAA]). METHODS: A retrospective cohort analysis of patients who underwent aortic intervention at Waikato Hospital, New Zealand between 2015-2020, comparing dissection (ATAAD) to TAA patients. MAD; ratio of MAD to standardised-points within the aorta; and MAD-to-height collected from computed tomography (CT)-scans of all patients was undertaken. Receiver operating characteristic (ROC)-analysis to determine cut-off point for each marker was undertaken together with multivariable logistic regression comparing both cohorts, cross-validated by propensity-score matched analysis. RESULTS: Cohort of 215 patients, 78 (36.3%) ATAAD and 137 (63.7%) TAA; median age at intervention 63.3 years, 52 (24.2%) females, both cohorts matched for size. Using the entire cohort, the MAD: sinus of Valsalva (SoV) ratio>1.06 (cut-off value) had 4.5-times greater association with ATAAD (95%CI 1.46-13.8) and a 0.1-unit increased conferred 1.45-times greater association with ATAAD (95%CI 1.00-2.08). MAD>55 mm only seen in 33.3% of ATAAD (n=26/78), and not associated with ATAAD (OR 1.88, 95%CI 0.64-5.51). Compared to MAD, MAD:SoV ratio had greater sensitivity (33% vs 73%), lower number-needed-to-treat (17.9 vs 2.7) and superior discrimination (area under the curve [AUC] 0.54 vs 0.71). Findings were consistent with propensity score matched analysis. CONCLUSIONS: MAD:SoV ratio significantly correlates with ATAAD (4.5 times), with superior sensitivity, discrimination, and attributable-risk-percentage compared to MAD alone.

Outcomes of Coronary Artery Bypass Grafting in Patients With Poor Myocardial Viability: A Systematic Review and Meta-Analysis of the Last Decade.

OBJECTIVES: Our objective is to assess whether the presence of myocardial viability is a predictor of mortality among patients undergoing coronary artery bypasss grafting (CABG) through a systematic review meta-analysis. METHODS: Comprehensive review of EMBASE and PubMed in accordance with PRISMA guidelines, including studies of patients undergoing CABG with assessment of myocardial viability and recorded long-term mortality, age and sex. Studies were restricted to the last decade, and data were stratified by imaging modality (magnetic resonance imaging [MRI] or nuclear medicine). Random-effects model for assessing pooled effect, heterogeneity assessment using Chi-square and I2 statistics, publication bias assessed by funnel plots and Egger's test. RESULTS: Meta-analysis of contemporary data (January 2010 to October 2020) yielded 3,621 manuscripts of which 92 were relevant, and 6 appropriate for inclusion with 993 patients. Pooled analysis showed that patients with non-viable myocardium undergoing CABG are at 1.34 times the risk of mortality compared to those with viable myocardium (95% CI 1.01-1.79, p=0.05). Subgroup analysis of the MRI or nuclear medicine modalities was not statistically significant and there was no confounding by age or sex in meta-regression. There was significant heterogeneity in imaging modality and diagnostic criteria, but heterogeneity between study findings was low with an I2 statistic of 29%. The risk of publication bias was moderate on the Newcastle-Ottawa Scale), but not statistically significant (Egger's Test coefficient=1.3, 95%CI -0.35-2.61, p=0.10). CONCLUSIONS: There is a multitude of methods for assessing cardiac viability for coronary revascularisation surgery, making meta-analyses fraught with limitations. Our meta-analysis demonstrates that the finding of non-viable myocardium can not be used draw conclusions for risk assessment in coronary surgery.

Branch-first continuous perfusion aortic arch replacement: insight into our results.

BACKGROUND: Aortic-arch surgery often necessitates interruption of perfusion conferring higher morbidity and mortality compared to other aortic segments. We describe our Branch-first continuous-perfusion aortic-arch replacement (BF-CPAR) technique which overcomes these shortcomings, describing technique, results and improved outcomes. METHODS: This represents the senior author's 15-year experience with BF-CPAR. Description of demographics, procedures and outcomes have been stratified by dissection and aneurysm etiology, with prediction of mortality, cerebrovascular events, renal failure, and end-organ ischemia undertaken using multivariable logistic regression analysis. RESULTS: From July 2005 to February 2021, 155 patients underwent BF-CPAR, 93 for aneurysms and 62 for dissections. Median age at intervention was 66.8 years, 96 (61.9%) male, 18 (11.6%) with history of previous dissection repair, and 49 (31.6%) on an emergent basis. We observed an overall mortality of 4.5% (N.=7) and stroke of 3.2% (N.=5). Comparing elective to urgent cases, the mortality and stroke rates were significantly lower at 0.0% and 1.9% versus 14.2% and 6.1% (risk differences: 14.3% and 2.3%, P<0.01) respectively. Predictors of mortality were age (1.11 per year, 95% CI: 1.00-1.23, P=0.05); of stroke were hypercholesterolemia (14.4, 1.84-111.9, P=0.01) and hypertension (0.07, 0.01-0.84, P<0.01); and of dialysis were dissection (6.60, 1.76-24.7, P<0.01). CONCLUSIONS: BF-CPAR is safe and adds to the armamentarium of aortic arch repair. In elective and uncomplicated acute-dissection cases, it has no mortality and low stroke (1.9%), and vital organ dysfunction risk. Its results which are comparable to many of the best currently reported series, is driven by avoidance of cerebral circulatory arrest and reduction of cardiac and visceral ischemic time.

Cardiac surgery simulation: a low-cost feasible option in an Australasian setting.

BACKGROUND: Simulation training is a useful adjunct to surgical training and education (SET) in Cardiothoracic Surgery yet training opportunities outside the Royal Australasian College of Surgery or industry-sponsored workshops are rare due to high cost and limited training faculty, time, assessment tools or structured curricula. We describe our experience in establishing a low-cost cardiac simulation programme. METHODS: We created low-cost models using hospital facilities, hardware stores, abattoirs and donations from industry. Three workshops were conducted on coronary anastomoses, aortic and mitral valve replacement. RESULTS: Whole porcine hearts were sourced from local farms. Industry donations of obsolete stock were used for suture and valve material-stations constructed using ironing-board, 2-L buckets and kebab-skewers. Suture ring holders were fashioned from recycled cardboard or donated. All participants were asked to complete pre and post simulation self-assessment forms. Across three workshops, 45 participants (57.8% female) with a median age 27 (interquartile range 24-31) attended. Training level consisted of nurses (8, 17.8%), medical students (17, 37.8%), residents/house officers (6, 13.3%) and registrars (14, 31.1%). There were improvements in knowledge of anatomy (mean difference 18%; 95% confidence interval 12%-24%), imaging (16%; 10%-22%) and procedural components (34%; 28%-42%); and practical ability to describe steps (30%; 24%-38%), partially (32%; 26%-38%) or fully complete (32%; 28%-38%) the procedure. CONCLUSIONS: Simulation-based training in cardiac surgery is feasible in a hospital setting with low overhead costs. It can benefit participants at all training levels and has the potential to be implemented in training hospitals as an adjunct to the SET programme.

Protein-losing enteropathy and plastic bronchitis after the Fontan procedure.

OBJECTIVES: Protein losing enteropathy and plastic bronchitis are severe complications in Fontan circulation, with 5-year survival ranging from 46% to 88%. We report risk factors and outcomes of protein losing enteropathy and plastic bronchitis in patients undergoing the Fontan. METHODS: We performed a retrospective analysis of 1561 patients from the Australia New Zealand Fontan Registry. Two end points were death and cardiac transplantation examined with Cox regression (if no competing risks) or cumulative incidence curves and cause-specific Cs regression. RESULTS: A total of 55 patients with protein losing enteropathy/plastic bronchitis were included. Their median age at the Fontan was 5.7 years, and time to onset after the Fontan for protein losing enteropathy was 5.0 years and plastic bronchitis was 1.7 years. Independent predictors for developing protein losing enteropathy/plastic bronchitis were right-ventricular morphology with hypoplastic left-heart syndrome (hazard ratio, 2.30; confidence interval, 1.12-4.74), older age at Fontan (hazard ratio, 1.13; confidence interval, 1.03-1.23), and pleural effusions after Fontan (hazard ratio, 2.43; confidence interval, 1.09-5.41); left-ventricular morphology was protective (hazard ratio, 0.36; confidence interval, 0.18-0.70). In the protein losing enteropathy/plastic bronchitis population, freedom from death or transplantation after protein losing enteropathy/plastic bronchitis diagnosis at 5, 10, and 15 years was 70% (confidence interval, 58-85), 65% (confidence interval, 51-83), and 43% (confidence interval, 26-73), respectively; only older age (hazard ratio, 1.23; confidence interval, 1.01-1.52) was an independent predictor. Twenty-six surgical interventions were performed in 20 patients, comprising Fontan revisions (n = 5), fenestrations (n = 11), Fontan conversions (n = 5), atrioventricular valve repairs (n = 3), and hepatic vein diversion (n = 2). CONCLUSIONS: Protein losing enteropathy and plastic bronchitis remain severe complications, preferably affecting patients with dominant right single ventricle, with older age at Fontan being a predictor of developing protein losing enteropathy/plastic bronchitis and poorer prognosis. Heart transplantation remains the ultimate treatment, with 30% dying or requiring transplantation within 5 years, and the remaining being stable for long periods.

What are the endovascular options and outcomes for repair of ascending aortic or aortic arch pathology?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'in patients with ascending aortic or aortic arch disease what are the outcomes with endovascular repair in terms of survival, complications and reintervention?' Altogether 585 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We found that the endovascular operative techniques with the greatest evidence were ascending aortic chimney grafts (AACs), branched thoracic endovascular aortic repair (bTEVAR) aortic grafts and fenestrated TEVAR (fTEVAR) aortic grafts. The best evidence available were small case-series or retrospective cohort studies (n < 100), with 1 systematic review, at a short follow-up period (range 0-5 years). Intraoperatively, these techniques have a high technical success rate (84-100%). We found rates of endoleak comparable between AAC (7.4-16%) and bTEVAR/fenestrated TEVAR (11.1-21.4%). Stroke rates are higher in bTEVAR (3.1-42% vs 1-26% in AACs), attributed to more proximal pathology and technically challenging procedures. Following the immediate postoperative period, the 30-day mortality is 0-10.8% and patency is 97-100%. Stroke and reintervention rates remain higher in the bTEVAR group (3.1-42.0% and 0.5-33.3%) compared to the AAC group (1.0-11.1% and 6.7-16.7%). The 3- and 5-year survival ranges from 59% to 90%, but is driven by non-aortic pathology in a high-risk population; 3-year freedom from aortic death is 93-97%. Patency is 97-100% at up to 3 years, conformation and supra-aortic occlusions thereafter remain unknown. We conclude that AACs, bTEVARs and fenestrated TEVARs are safe endovascular options in high-risk elective patients, with results comparable to open or hybrid repair. They remain unverified in acute settings or in patients fit for open intervention.