Search

Cardiac transplantation remains the gold standard therapy for select patients with end-stage heart failure and outcomes have improved significantly over the past few decades. We report the 5-year contemporary experience of cardiac transplantation in Western Australia, one of the most remote transplant centres worldwide.Patients undergoing isolated cardiac transplant at Fiona Stanley Hospital (FSH) from February 2015 until April 2021 were included. Donor details were collected using donor electronic records (Donate Life, Australia). Recipient data was collated from electronic medical records at FSH and the Australia and New Zealand Society of Cardiothoracic Surgery database. The primary outcome measure was all-cause mortality. Secondary outcome measures included postoperative intensive care and total hospital length of stay and rates of acute kidney injury, rejection, serious infections, and cardiac allograft vasculopathy. Frailty indices were also assessed.A total of 60 patients were included (mean age 53±14 yrs, 66.7% male). The commonest indication for transplant was a non-ischaemic cardiomyopathy (46.7%). Mean donor age was 35±12 years and median donor ischaemia time was 171 minutes (IQR=138-240). After median follow-up of 3.7 years, there were no mortalities. Postoperative renal failure occurred in 21 (35.0%) patients, pneumonia in four (6.7%), deep sternal wound infection in three (5.1%), acute rejection in 17 (28.3%) and cardiac allograft vasculopathy (CAV) in 23 (38.3%).With recipient and donor criteria comparable to national and international standards, compounded by the challenges of geographic isolation, we report the first published data on contemporary outcomes post isolated cardiac transplantation in Western Australia.

Pulmonary hypertension (PH) due to left heart disease (LHD) is a frequent complication of heart failure (HF) and is associated with exercise intolerance, poor quality of life, increased risk of hospitalisations, and reduced overall survival. Since the recent Sixth World Symposium on Pulmonary Hypertension in 2018, there have been significant changes in the hemodynamic definitions and clinical classification of PH-LHD. PH-LHD can be subdivided into (1) isolated postcapillary PH (IpcPH) and (2) combined precapillary and postcapillary PH (CpcPH). This categorisation of PH-LHD is important because CpcPH shares certain pathophysiologic, clinical, and hemodynamic characteristics with pulmonary arterial hypertension and is associated with worse outcomes compared with IpcPH. A systematic approach using clinical history and noninvasive investigations is required in the diagnosis of PH-LHD. Right heart catheterisation with and without provocative testing is performed in expert centres and is indicated in selected individuals. Although the definition of IpcPH and CpcPH is based on measurements made with right heart catheterisation, distinguishing between these two entities is not always necessary. Despite strong evidence for medical therapy in patients with pulmonary arterial hypertension, those options have limited benefit in PH-LHD. Expert PH centres in Canada have been established to provide ongoing care for the more complex patient subgroups.

Background and objective Pleural infection is a clinical challenge; its microbiology can be complex. Epidemiological and outcome data of pleural infection in adult Australians are lacking. We describe the bacteriology and clinical outcomes of Australian adults with culture-positive pleural infection (CPPI) over a 6-year period. Methods Cases with CPPI were identified through Western Australian public hospitals electronic record. Culture isolates, admission dates, vital status, co-morbidities, radiology, blood and pleural fluid tests were extracted. Results In total, 601 cases (71.4% males; median age: 63 years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%) cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer, were common (65.2%). Radiological evidence of pneumonia was present in only 43.8% of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured, Streptococcus species (32.9%) especially viridans streptococci group were most common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA-CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006). Conclusion This is the first large multicentre epidemiological study of pleural infection in Australian adults and includes the largest cohort of HA-CPPI published to date. CPPI is caused by a diverse range of organisms which vary between CA and HA sources. CPPI is a poor prognostic indicator both in the short term and in the subsequent 12 months.

Purpose Intravascular ultrasound (IVUS) assessment of cardiac allograft vasculopathy (CAV) provides diagnostic and prognostic information. Multivessel analysis has high sensitivity for detecting CAV, but is time consuming, costly and associated with procedural risks compared to single-vessel examination. We evaluated the regional distribution and plaque characteristics of CAV to guide clinical evaluation by IVUS. Methods Consecutive heart transplant recipients referred for coronary angiography were prospectively evaluated with multivessel IVUS. Quantitative IVUS analysis was performed for every 1 mm axial slice to determine average maximal intimal thickness, intimal area and percentage intimal area. Virtual histology was utilized for plaque characterization. Results Forty patients completed evaluation at 4.8 ± 5.8 years post-transplant: mean age 56 ± 14 years, 31 (78%) male. Angiographic disease was present in 14 (35%) patients: 9 (23%) CAV1, 2 (5%) CAV2, 3 (8%) CAV3. Maximal stenosis was greater in the LAD (median 34% (IQR 20, 63) vs. 19% (IQR 0, 29) for LCx, 0% (IQR 0, 18) for RCA, (p=0.001)) and proximal segments (median 17% (IQR 12, 29) vs. 13% (IQR 9, 23) for mid, 12% (IQR 8, 16) for distal segments, p=0.005). A total of 268 segments in 101 vessels (40 left anterior descending (LAD), 35 circumflex (LCx), 26 right coronary artery (RCA)) were analyzed with IVUS. Mean coronary length examined was 64 ± 15 mm. Intimal disease on IVUS was greater in the LAD and proximal coronary segments (Table). On virtual histology, plaque composition was predominantly mixed atheromatous fibrotic and more prevalent in the LAD (72%) vs. LCx (54%) and RCA (42%), p=0.043. There was no isolated fibrotic plaque and low 13% prevalence of vulnerable thin cap fibroatheroma plaque. Conclusion There is heterogeneous distribution of CAV with high disease burden in the LAD and proximal coronary segments. Single-vessel IVUS examination for CAV, beginning in the LAD could avoid risks of multivessel examination.

Self-Management of Acute Myocardial Infarction Severe chest pain and dizziness developed in a 44-year-old nurse, the only medical professional at a remote post in Australia. He obtained his own ECG, which showed ST-segment elevation myocardial infarction. With remote instruction, he treated himself with fibrinolysis.

Childhood leukemia survivors commonly develop late-onset cardiovascular disease after treatment with anthracyclines. Resting echocardiogram is the standard procedure for monitoring cardiac health but this method may not be sensitive enough to detect subclinical injury. Exercise echocardiography may provide a viable alternative.Nineteen (9 males; age, 19 ± 3 yr) anthracycline-treated survivors of childhood leukemia and 17 (8 males) healthy individuals of similar age (22 ± 2 yr) were recruited. All survivors had normal resting echocardiography upon recruitment. Exercise echocardiography was performed using contemporary imaging techniques. Flow-mediated dilation (FMD), body composition, and cardiorespiratory fitness (V˙O2peak) were assessed to determine predisposition to additional disease.Mitral valve peak flow velocity in late diastole (interaction, P = 0.007) increased from rest in survivors (P = 0.023) and controls (P = 0.020) immediately postexercise but did not recover again in the survivors (exercise-recovery, P = 0.784) after recuperation. Consequently, E/A ratio (interaction, P0.001) was lower in the survivors at recovery (P0.001). Survivors had reduced FMD (7.88 ± 1.70 vs 9.65 ± 2.83; P = 0.030), maximal and recovery HR (P = 0.001; P0.001), minute ventilation (P0.001), and V˙O2peak (absolute, 2.64 ± 0.62 vs 3.14 ± 0.74 L·min, P = 0.034; relative, 36.78 ± 11.49 vs 45.14 ± 6.80 mL·kg·min; P = 0.013) compared with controls. They also had higher total body fat (percentage, P = 0.034; mass, P = 0.024) and fat mass in the central (P = 0.050), peripheral (P = 0.039) and visceral (P0.001) regions. Survivors matched controls with regard to height (173.0 ± 7.8 cm vs 173.8 ± 9.1 cm; P = 0.796), body mass (76.16 ± 19.05 kg vs 70.07 ± 13.96 kg; P = 0.287) and body mass index (25.2 ± 5.1 vs 22.9 ± 2.7; P = 0.109).Exercise echocardiography unmasked subclinical diastolic dysfunction that may indicate late anthracycline toxicity in apparently healthy survivors of childhood leukemia. Presence of secondary risk factors indicates increased predisposition to comorbidities and highlights the importance of assessing cardiovascular health during follow-up.

Cardiac allograft vasculopathy (CAV) is a unique accelerated form of coronary vascular disease affecting heart transplant recipients. This complication is a significant contributor to medium- to long-term post-transplant morbidity and mortality. There is a high prevalence of CAV with approximately one in three patients developing CAV by 5 years post-transplant. Morphologically, CAV is characterized by concentric coronary intimal hyperplasia in both the epicardial arteries and intramural microvasculature. Although several immune and non-immune factors have been identified, their precise pathogenic mechanisms, interactions, and relative importance in the development of CAV are not well defined. The advent of improved imaging surveillance modalities has resulted in earlier detection during the disease process. However, overall management of CAV remains challenging due to paucity of treatment. This review aims to discuss key concepts on the pathogenesis of CAV and current management strategies, focusing on the use of mammalian target of rapamycin inhibitors.

Pleural infection is a clinical challenge; its microbiology can be complex. Epidemiological and outcome data of pleural infection in adult Australians are lacking. We describe the bacteriology and clinical outcomes of Australian adults with culture-positive pleural infection (CPPI) over a 6-year period.Cases with CPPI were identified through Western Australian public hospitals electronic record. Culture isolates, admission dates, vital status, co-morbidities, radiology, blood and pleural fluid tests were extracted.In total, 601 cases (71.4% males; median age: 63 years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%) cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer, were common (65.2%). Radiological evidence of pneumonia was present in only 43.8% of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured, Streptococcus species (32.9%) especially viridans streptococci group were most common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA-CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006).This is the first large multicentre epidemiological study of pleural infection in Australian adults and includes the largest cohort of HA-CPPI published to date. CPPI is caused by a diverse range of organisms which vary between CA and HA sources. CPPI is a poor prognostic indicator both in the short term and in the subsequent 12 months.

The ability to image the brain of a freely moving rodent using motion-compensated PET presents many exciting possibilities for exploring the links between brain function and behavior. Markerless optical approaches for pose estimation have several potential advantages over marker-based methods: improved accuracy and increased range of detectable motion; no `decoupling' of marker and head motion; and no acclimatization of the animals to attached markers. Our aim in this work was to describe and validate a silhouette-based multi-camera method for estimating the pose of a rat. Random-walk and K-means clustering approaches were very adaptable to uneven lighting and generally provided excellent object segmentations. In obtaining a high quality rat model, shape-from-silhouette and laser scanning both resulted in useful models; laser scanning provided sub-millimeter resolution with very few artifacts and was the method of choice. In our experimental validation, the 3D-2D (model-silhouette) optimization clearly converged to sub-degree and sub-millimeter alignment of the measured and estimated silhouettes. The average discrepancy between test points transformed using the estimated versus ground-truth poses was 0.94 mm ± 0.51 mm. This investigation focused on rigid motion of a rat phantom as a proof-of-principle of the technique. Future work will focus on investigating the potential of designing a non-rigid rodent body model in order to apply the method to a freely moving animal during PET imaging.

Background Animal African trypanosomosis (AAT) is a neglected tropical disease which imposes a heavy burden on the livestock industry in Sub-Saharan Africa. Its causative agents are Trypanosoma parasites, with T. congolense and T. vivax being responsible for the majority of the cases. Recently, we identified a Nanobody (Nb474) that was employed to develop a homologous sandwich ELISA targeting T. congolense fructose-1,6-bisphosphate aldolase (TcoALD). Despite the high sequence identity between trypanosomatid aldolases, the Nb474-based immunoassay is highly specific for T. congolense detection. The results presented in this paper yield insights into the molecular principles underlying the assay’s high specificity. Methodology/Principal findings The structure of the Nb474-TcoALD complex was determined via X-ray crystallography. Together with analytical gel filtration, the structure reveals that a single TcoALD tetramer contains four binding sites for Nb474. Through a comparison with the crystal structures of two other trypanosomatid aldolases, TcoALD residues Ala77 and Leu106 were identified as hot spots for specificity. Via ELISA and surface plasmon resonance (SPR), we demonstrate that mutation of these residues does not abolish TcoALD recognition by Nb474, but does lead to a lack of detection in the Nb474-based homologous sandwich immunoassay. Conclusions/Significance The results show that the high specificity of the Nb474-based immunoassay is not determined by the initial recognition event between Nb474 and TcoALD, but rather by its homologous sandwich design. This (i) provides insights into the optimal set-up of the assay, (ii) may be of great significance for field applications as it could explain the potential detection escape of certain T. congolense strains, and (iii) may be of general interest to those developing similar assays., Author summary Sub-Saharan Africa is plagued by many diseases, which impede its socio-economical development. One of these diseases, Animal African Trypanosomosis, affects livestock and is caused by the parasites of the Trypanosoma genus (T. vivax and T. congolense). Animal African Trypanosomosis leads to considerable economic losses and renders sustainable livestock industry in Sub-Saharan Africa very difficult. In order to proceed with the selective treatment of infected animals, they need to be properly diagnosed. We recently described the use of an assay to specifically detect T. congolense infections in both experimentally and naturally infected animals. The diagnostic assay employs a Nanobody (Nb), which is the smallest antigen-binding unit derived from camelid heavy-chain only antibodies. Our previous results showed that the Nb-based diagnostic test specifically recognizes T. congolense fructose-1,6-bisphosphate aldolase, a glycolytic enzyme that is well conserved amongst other Trypanosoma species. In this paper, we studied the molecular mechanisms underlying the high specificity of the Nb-based diagnostic assay. The principles derived from this work may be important for the design and improvement of similar diagnostic tests.

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.