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.

Calcified left ventricular apical aneurysm with intramural thrombus: a case report.

Background: Left ventricular aneurysms (LVAs) are a well-appreciated complication of acute myocardial infarction. Ventricular aneurysms involving the left ventricle (LV) typically evolve as a result of anterior myocardial infarction and are associated with greater morbidity, complication rates, and hospital resource utilization. Incidence of LVA is decreasing with advent of modern reperfusion therapies; however, in the setting of excess morbidity, clinicians must maintain an appreciation for their appearance to allow timely diagnosis and individualized care. Case summary: This case report describes the clinical history, investigation, appearance, and management of a patient with calcified apical LVA with history of previous anterior ST-elevation myocardial infarction. The patient was initially admitted for elective coronary angiography in the setting of worsening exertional dyspnoea and subsequently underwent coronary artery bypass graft, aneurysm resection, and LV reconstruction. Discussion: Left ventricular aneurysms are an uncommon complication experienced in the modern era of acute myocardial infarction and current reperfusion therapies, but remain an important cause of excess morbidity and complication. Evidence-based guidelines for the diagnosis, workup, and subsequent management of LVAs are lacking. The imaging findings presented in this case serve as an important reminder of the appearance of LVAs so that timely diagnosis and individualized care considerations can be made.

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.

Hypertrophic cardiomyopathy with anteriorly directed mitral regurgitation is a red flag for concomitant pathology: a case report.

Background: Hypertrophic cardiomyopathy (HCM) is often linked to systolic anterior motion (SAM) of the mitral valve, typically resulting in a posteriorly directed mitral regurgitation (MR) jet. An anteriorly directed MR jet suggests additional mitral valve pathology that may not be resolved by myectomy alone. Case summary: A 58-year-old construction worker with no significant medical history experienced a syncopal event and was admitted to the emergency department with acute pulmonary oedema. A systolic murmur was investigated with a trans-thoracic echocardiogram that revealed severe MR with an unusual anteriorly directed MR jet and a possible flail segment of the posterior leaflet. This finding was further characterized with a trans-oesophageal echocardiogram that revealed severe asymmetric septal hypertrophy with SAM of the mitral valve, severe mitral regurgitation into a dilated left atrium with pulmonary vein flow reversal not caused by HCM-associated SAM, and a markedly abnormal mitral valve with flail and prolapse. The patient underwent successful cardiac surgery, including mitral valve repair and septal myectomy. The patient's recovery was uneventful, allowing for a return to work within a month post-surgery. Discussion: The anteriorly directed MR jet served as a red flag, leading to the discovery of an independent mitral valve pathology that required surgical intervention beyond the expected treatment for SAM-associated HCM. This case highlights the complexity of assessing MR in patients with HCM and underscores the importance of characterizing MR jet direction in diagnosing additional mitral valve diseases.

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.

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.

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.

Ambulatory short-term mechanical circulatory support: facilitates recovery and prepares patients for definitive therapy.

Short-term mechanical circulatory support (ST-MCS) devices have been traditionally deployed in patients with cardiogenic shock, advanced heart failure, cardiovascular collapse, and cardiorespiratory failure. Limitations of the mechanical support devices are typically related to mobility of the patient since the access is frequently through femoral vasculature. This limits the time the patient can be supported by mechanical circulatory support (MCS). We describe deployment of ST-MCS using alternate access such as the subclavian/axillary artery that facilitates ambulation of the patient. These include the deployment of intra-aortic balloon pump (IABP) through the subclavian artery, Impella pump through the axillary/subclavian artery, and extracorporeal membrane oxygenation (ECMO) using the subclavian artery and jugular vein.

Smaller Return Cannula in Venoarterial Extracorporeal Membrane Oxygenation Does Not Increase Hemolysis: A Single-Center, Cohort Study.

The aim of this study was to explore the association between arterial return cannula diameter and hemolysis during peripheral VA ECMO. We identified 158 adult patients who received peripheral VA ECMO at our institution from the national ECMO database (EXCEL) between January 2019 and July 2021. We classified patients into a small cannula group (15 Fr diameter, n = 45) and a large cannula group (≥17 Fr diameter, n = 113), comparing incidences of clinical hemolysis and plasma free hemoglobin ( pf Hb). Moderate hemolysis is defined as having pf Hb 0.05-0.10 g/L and severe hemolysis as having pf Hb >0.10 g/L sustained for at least two consecutive readings or leading to a circuit change. There were no significant differences in rates of moderate hemolysis between small and large cannula groups (1 vs . 6; p = 0.39) and severe hemolysis (0 vs . 3; p = 0.27), nor was the pf Hb level significantly different at 4 hours (0.086 ± 0.096 vs . 0.112 ± 0.145 g/L; p = 0.58) and at 24 hours (0.042 ± 0.033 vs . 0.051 ± 0.069 g/L; p = 0.99). There were no increased rates of hemolysis when comparing small versus large arterial return cannula diameter in peripheral VA ECMO.

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.

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.

Characteristics of Radial Artery Coronary Bypass Graft Failure and Outcomes Following Subsequent Percutaneous Coronary Intervention.

BACKGROUND: When patients with prior coronary artery bypass grafting (CABG) undergo percutaneous coronary intervention (PCI), targeting the native vessel is preferred. Studies informing such recommendations are based predominantly on saphenous vein graft (SVG) PCI. There are few data regarding arterial graft intervention, particularly to a radial artery (RA) graft. OBJECTIVES: The aim of this study was to report the characteristics of arterial graft stenoses and evaluate the feasibility of RA PCI. METHODS: This study included 2,780 consecutive patients with prior CABG undergoing PCI between 2005 and 2018 who were prospectively enrolled in the MIG (Melbourne Interventional Group) registry. Data were stratified by PCI target vessel. RA graft PCI was compared with both native vessel (native PCI) and SVG PCI. Internal mammary graft PCI data were reported. The primary outcome was 3-year mortality. RESULTS: Overall, 1,928 patients (69.4%) underwent native PCI, 716 (25.6%) SVG PCI, 86 (3.1%) RA PCI, and 50 (1.8%) internal mammary graft PCI. Compared with SVG PCI, the RA PCI cohort presented earlier after CABG, less frequently had acute coronary syndrome, and more commonly had ostial or distal anastomosis intervention (P < 0.005 for all). Compared with patients who underwent native PCI, those who underwent RA PCI were more likely to have diabetes and peripheral vascular disease (P < 0.001 for both) and to present with non-ST-segment elevation myocardial infarction (P = 0.010). The RA PCI group had no perforations or in-hospital myocardial infarctions, though no significant difference was found in periprocedural outcomes compared with either native or SVG PCI. No differences were found between RA PCI and either native or SVG PCI in 30-day outcomes or 3-year mortality. CONCLUSIONS: Presenting and lesion characteristics differed between patients undergoing arterial compared with SVG PCI, implying a varied pathogenesis of graft stenosis. RA PCI appears feasible, safe, and where anatomically suitable, may be a viable alternative to native PCI.

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.