Near-infrared spectroscopy as a novel method of ex vivo bladder cancer tissue characterisation.

OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Flow capabilities of arterial and drainage cannulae during venoarterial extracorporeal membrane oxygenation: A simulation model.

BACKGROUND: Large cannulae can increase cannula-related complications during venoarterial extracorporeal membrane oxygenation (VA ECMO). Conversely, the ability for small cannulae to provide adequate support is poorly understood. Therefore, we aimed to evaluate a range of cannula sizes and VA ECMO flow rates in a simulated patient under various disease states. METHODS: Arterial cannulae sizes between 13 and 21 Fr and drainage cannula sizes between 21 and 25 Fr were tested in a VA ECMO circuit connected to a mock circulation loop simulating a patient with severe left ventricular failure. Systemic and pulmonary hypertension, physiologically normal, and hypotension were simulated by varying systemic and pulmonary vascular resistances (SVR and PVR, respectively). All cannula combinations were evaluated against all combinations of SVR, PVR, and VA ECMO flow rates. RESULTS: A 15 Fr arterial cannula combined with a 21 Fr drainage cannula could provide >4 L/min of total flow and a mean arterial pressure of 81.1 mmHg. Changes in SVR produced marked changes to all measured parameters, while changes to PVR had minimal effect. Larger drainage cannulae only increased maximum circuit flow rates when combined with larger arterial cannulae. CONCLUSION: Smaller cannulae and lower flow rates could sufficiently support the simulated patient under various disease states. We found arterial cannula size and SVR to be key factors in determining the flow-delivering capabilities for any given VA ECMO circuit. Overall, our results challenge the notion that larger cannulae and high flows must be used to achieve adequate ECMO support.

Ultrasound Guidance for Transradial Access in the Cardiac Catheterisation Laboratory: A Systematic Review of the Literature and Meta-Analysis.

BACKGROUND: Although ultrasound (US) guidance for vascular access has been widely adopted, its use for transradial access (TRA) in the cardiac catheterisation laboratory is rare. There is a perception that US guidance does not offer a clinically relevant benefit over traditional palpation-guided TRA, amplified by inconsistent findings of individual studies. METHOD: A systematic review of MEDLINE, EMBASE and the Cochrane Library identified studies comparing US to palpation-guided TRA for cardiac catheterisation. Studies evaluating radial artery (RA) cannulation for any other reason were excluded. Event rates and risk ratios (RRs) were pooled for meta-analysis. Access failure was the primary outcome. A random-effects model was used for analysis. RESULTS: Of the 977 records screened, four studies with a total of 1,718 patients (861 US-guided and 864 palpation-guided procedures) were included in the meta-analysis. Most procedures were elective. The pooled analysis showed US guidance significantly lowered the risk of access failure (RR 0.45; 95% confidence interval [CI] 0.21-0.97; p=0.04). Heterogeneity was moderate (I2=51.2%; p=0.105). There was a strong trend to improved first-pass success with US (RR 1.29; 95% CI 1.00-1.66; p=0.05; I2=83.8%), although no differences were found in rates of difficult access (RR 0.29; 95% CI 0.07-1.18; p=0.09; I2=88.3%). Salvage US guidance was successful in 30/41 (73.2%) patients following failed palpation-guided TRA. No differences were found in already low complication rates including RA spasm (RR 1.18; 95% CI 0.70-1.99; p=0.53; I2=0.0%) and bleeding (RR 1.32; 95% CI 0.46-3.80; p=0.60; I2=0.0%). CONCLUSIONS: US guidance was found to improve TRA success in the cardiac catheterisation laboratory. Further investigation is necessary to determine whether routine, selective, or salvage use of US confers the most RA protection, patient satisfaction, and overall clinical benefit. (PROSPERO registration: CRD42022332238).

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.

Hemodynamics of small arterial return cannulae for venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (ECMO) provides mechanical support for critically ill patients with cardiogenic shock. Typically, the size of the arterial return cannula is chosen to maximize flow. However, smaller arterial cannulae may reduce cannula-related complications and be easier to insert. This in vitro study quantified the hemodynamic effect of different arterial return cannula sizes in a simulated acute heart failure patient. METHODS: Baseline support levels were simulated with a 17 Fr arterial cannula in an ECMO circuit attached to a cardiovascular simulator with targeted partial (2.0 L/min ECMO flow, 60-65 mm Hg mean aortic pressure-MAP) and targeted full ECMO support (3.5 L/min ECMO flow and 70-75 mm Hg MAP). Return cannula size was varied (13-21 Fr), and hemodynamics were recorded while keeping ECMO pump speed constant and adjusting pump speed to restore desired support levels. RESULTS: Minimal differences in hemodynamics were found between cannula sizes in partial support mode. A maximum pump speed change of +600 rpm was required to reach the support target, and arterial cannula inlet pressure varied from 79 (21 Fr) to 224 mm Hg (13 Fr). The 15 Fr arterial cannula could provide the target full ECMO support at the targeted hemodynamics; however, the 13 Fr cannula could not due to the high resistance associated with the small diameter. CONCLUSIONS: A 15 Fr arterial return cannula provided targeted partial and full ECMO support to a simulated acute heart failure patient. Balancing reduced cannula size and ECMO support level may improve patient outcomes by reducing cannula-related adverse events.

The Effects of Targeted Changes in Systemic Blood Flow and Mean Arterial Pressure on Urine Oximetry During Cardiopulmonary Bypass.

OBJECTIVES: Poor medullary oxygenation is implicated in the evolution of acute kidney injury. The authors sought to determine if increasing systemic flow and mean arterial pressure could improve urine oxygen tension (PuO2) measured in the bladder, a surrogate of kidney medullary oxygenation, in patients undergoing on-pump cardiac surgery. DESIGN: Randomized crossover study. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty adult patients undergoing cardiopulmonary bypass (CPB) with expected cross-clamp time of >60 minutes and estimated glomerular filtration rate of >30 mL/min/1.73m2. INTERVENTIONS: Sequential 20-minute periods of 2 interventions: Intervention H ("High") or Intervention N ("Normal"). The order of interventions was determined by randomization. Intervention H: targeted CPB flow 3.0 L/min/m2 and mean arterial pressure (MAP) 80 mmHg. Intervention N: targeted CPB flow 2.4 L/min/m2 and MAP 65 mmHg. MEASUREMENTS AND MAIN RESULTS: PuO2 was measured by an oxygen sensor introduced into the bladder via a urinary catheter. Clear separation was achieved in CPB flow and MAP between intervention periods (p < 0.001 for group-time interaction). PuO2 during Intervention H was higher than during Intervention N (p < 0.001 for group-time interaction). After 17 minutes, PuO2 was statistically higher in Intervention H at each time point. There were no differences in markers of hemolysis between interventions. CONCLUSIONS: PuO2 was higher when systemic flow and MAP were increased during CPB. These findings suggest that PuO2 is responsive to changes in hemodynamics and that higher flow and pressure may improve medullary oxygenation.

Brian Fowell Buxton (15/04/1940-20/05/2022)-Outstanding Achievements and Personal Memories.

Brian F. Buxton, one of Australia's greatest cardiac surgeons, died in May 2022, aged 82 years. In June 2022, a memorial celebration of Brian's life was held in Melbourne, Australia, attended by 550 colleagues and friends from many walks of life-not only "medical people" but also friends involved in Brian's sailing and hiking activities. This Special Article includes an introduction from Professor Jayme Bennetts, President of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS), an abridged version of a memorial address by Professor James Tatoulis and contributions from two other long-term professional colleagues and personal friends of Buxton, Professor Jaishankar Raman and Professor Franklin Rosenfeldt, founding editor of Heart, Lung and Circulation. Buxton was an outstanding and pioneering surgeon, clinical leader, and good friend to many. The Brian F. Buxton Cardiac and Thoracic Aortic Surgery Unit in Melbourne, Australia, is now so named in honour of his outstanding achievements and as a legacy. Vale Brian F. Buxton.

Factor Xa Inhibition for the Treatment of Venous Thromboembolism Associated With Cancer: A Meta-Analysis of the Randomised Controlled Trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Until recently, guidelines recommended the use of low-molecular weight heparin (LMWH) as standard of care for VTE in patients with cancer. Despite the proven efficacy of direct oral anticoagulants (DOACs) for treatment of VTE, there is equipoise supporting their use in cancer patients. METHODS: A systematic review of PubMed, Medline and EMBASE identified four randomised controlled trials (RCTs) in patients with cancer and VTE comparing a factor Xa inhibitor (FXaI) to LMWH. A meta-analysis was performed with a primary outcome of VTE recurrence and key secondary outcomes of major bleeding, clinically relevant non-major bleeding (CRNMB) and gastrointestinal (GI) bleeding. RESULTS: Four RCTs with 2,907 patients were included. 1,451 patients were randomised to FXaI and 1,456 to LMWH. VTE recurrence was lower in the FXaI group (RR 0.62, 95%CI 0.44-0.87; p=0.01; I2=24.90), with an absolute risk difference of -4% equating to a number needed to treat of 25 for prevention of recurrent VTE with FXaI. No significant difference in major bleeding was noted between groups (RR 1.33, 95%CI 0.84-2.11; p=0.23). Rates of GI bleeding (RR 1.87, 95%CI 1.06-3.29; p=0.03) and CRNMB (RR 1.57, 95%CI 1.11-2.23; p=0.01) were greater with FXaIs. CONCLUSION: In patients with cancer and VTE, the rate of VTE recurrence was significantly lower with FXaI than with LMWH without an increased risk of major bleeding. Our data supports the use of FXaIs as the standard of care for the treatment of VTE in this population.

Opioid Prescription After Cardiac Surgery.

OBJECTIVES: To characterise short-term and long-term opioid prescription patterns after cardiac surgery. DESIGN, SETTING AND PARTICIPANTS: We obtained data from a single Australian tertiary hospital from November 2012 to July 2019 and included 2,205 patients who underwent a primary cardiac surgical procedure. MAIN OUTCOME AND MEASURES: The primary outcome was the dose of opioids at hospital discharge. Secondary outcomes included factors associated with high dose opioid prescriptions and persistent opioids use after cardiac surgery. RESULTS: Overall, 76.4% of study patients were prescribed opioids at hospital discharge, with a median discharge prescription of 150 mg oral morphine equivalents. Moreover, 52.8% of discharge opioid prescriptions were as slow-release formulations and 60.0% of all discharge prescriptions were for patients who had received no opioids the day before discharge. In the subset of our patients with long-term data, 14.0% were still receiving opioids at 3-12 months after cardiac surgery. CONCLUSIONS: In cardiac surgical patients, opioid prescriptions at discharge were common, most were at higher than recommended doses and more than half were slow-release formulations. Such prescription was associated with one in seven patients continuing to receive opioids 3-12 months after surgery.

Comparative liquid chromatography/tandem mass spectrometry lipidomics analysis of macaque heart tissue flash-frozen or embedded in optimal cutting temperature polymer (OCT): Practical considerations.

RATIONALE: Biobanks of patient tissues have emerged as essential resources in biomedical research. Optimal cutting temperature compound (OCT) blends have shown to provide stability to the embedded tissue and are compatible with spectroscopic methods, such as infrared (IR) and Raman spectroscopy. Data derived from omics-methods are only useful if tissue damage caused by storage in OCT blends is minimal and well understood. In this context, we investigated the suitability of OCT storage for heart tissue destined for liquid chromatography/tandem mass spectrometry (LC/MS/MS) lipidomic studies. METHODS: To determine the compatibility of OCT storage with LC/MS/MS lipidomics studies. The lipid profiles of macaque heart tissue snap-frozen in liquid nitrogen or stored in an OCT blend were evaluated. RESULTS: We have evaluated a lipid extraction protocol suitable for OCT-embedded tissue that is compatible with LC/MS/MS. We annotated and evaluated the profiles of 306 lipid species from tissues stored in OCT or liquid nitrogen. For most of the lipid species (95.4%), the profiles were independent of the storage conditions. However, 4.6% of the lipid species; mainly plasmalogens, were affected by the storage method. CONCLUSIONS: This study shows that OCT storage is compatible with LC-MS/MS lipidomics of heart tissue, facilitating the use of biobanked tissue samples for future studies.

Extracorporeal membrane oxygenation in the management of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) is a type of systematic vasculitis that primarily involves the lung and kidney. Diffuse alveolar hemorrhage (DAH) and associated acute respiratory failure are uncommon but devastating complications of GPA. Experience in using extracorporeal membrane oxygenation (ECMO) to manage DAH caused by GPA is limited. We report two GPA patients with DAH that were successfully managed using ECMO support. Examining 13 cases identified in the literature and two of our own, we observed that most patients experienced rapid deterioration in respiratory function in conjunction with a precedent respiratory infection. All 15 patients received veno-venous ECMO support. The median duration of ECMO support was 11 days (interquartile range: 7.5-20.75 days). Bleeding was the most common complication, seen in four (26.7%) cases. All patients were successfully weaned off ECMO after a median length of hospital stay of 42 days (interquartile range: 30-78 days). We demonstrated that the use of ECMO is a reasonable and effective support option in the management of GPA patients with DAH. The risk of bleeding is high but maybe reduced using a lower anticoagulation goal.

SMARTphone Based Cardiovascular Risk Reduction in BREAST Cancer Patients (SMART-BREAST): A Randomised Controlled Trial Protocol.

INTRODUCTION: Breast cancer survivors are at greater risk for cardiovascular-related mortality compared to women without breast cancer. Accordingly, attention to reducing the risk of cardiovascular disease must be a priority in the long-term management of these patients. With the exponential rise in cancer survivors, there is a need for innovative cardio-oncology programs. This paper describes the study design of a randomised controlled trial assessing the effectiveness of a smartphone-based cardiovascular risk reduction program in improving physical activity and cardiovascular health in patients undergoing treatment for breast cancer. METHODS AND ANALYSIS: The aim of this study is to assess the efficacy and usability of a smartphone-based model of care for exercise promotion, cardiovascular risk reduction and community engagement in women undergoing treatment for breast cancer. This will be achieved by testing our personalised smartphone application "BreastMate", as an adjunct to standard care in a single-blinded, parallel, randomised controlled trial. The primary outcome of the trial is change in exercise capacity, as measured by the 6-minute walk test distance at 12 months compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status and quality of life, received dose intensity of chemotherapy and major adverse cardiovascular events. ETHICS: Multicentre ethical approval has been granted by the Austin Hospital (HREC/47081/Austin/2018). DISSEMINATION OF RESULTS: The analysed results will be published in a peer reviewed journal on completion of the clinical trial. REGISTRATION DETAILS: SMART-BREAST has been prospectively registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR12620000007932).

Early complications of biologic extracellular matrix patch after use for femoral artery repair.

BACKGROUND: The CorMatrix (CorMatrix Cardiovascular, Roswell, Ga) biologic extracellular patch derived from porcine small intestinal mucosa provides a biologic scaffold for cellular ingrowth and eventual tissue regeneration. It has been used in a variety of applications, including cardiac and vascular repair procedures. METHODS: CorMatrix was used as a patch arterioplasty for femoral artery repair in conjunction with endarterectomy for seven separate procedures in six patients (one patient underwent staged, bilateral femoral procedures). RESULTS: Patients were a median age of 67 years (interquartile range, 3.6 years). Six of seven procedures (86%) were performed on male patients. There were no operative deaths. Three of seven procedures (43%) resulted in significant early complications. Two procedures (29%) resulted in catastrophic biologic extracellular matrix patch disruption (11 and 19 days after initial procedure), requiring emergency exploration, patch removal, and definitive repair with vein patch arterioplasty. Both patches demonstrated an absence of growth on culture. One procedure (14%) resulted in groin pseudoaneurysm formation. Use of the CorMatrix patch was suspended upon recognition of significant complications. CONCLUSIONS: Use of CorMatrix patch in the femoral artery position demonstrates a high incidence of early postoperative complications, including catastrophic patch disruption and pseudoaneurysm formation.