2021 ResearchFest Infectious Diseases and Medical Imaging

2021 ResearchFest Infectious Diseases and Medical Imaging posters and videos
Search the pdf for keywords, author name etc
Infectious Diseases, Medical Imaging These posters or presentations are available at the padlet https://padlet.com/ResearchFest/2021_IDandMedIm The numbers in the left column are the position of the work in the display
Authors Title of abstract keywords
ID02 Lee W. Chong, Sylvia J. Gong, Aisea F. Veamatahua, Rachel Mulligan, George Rouvalis, Graeme J. O'Keefe, Kenneth Young, Uwe Ackermann, Andrew M. Scott
Internal Auditing of Local Shields for Radiopharmaceutical Procedures
Radiation Safety, Lead, Molecular Imaging
ID03 George Rouvalis, Sylvia J. Gong, Graeme J. O'Keefe, Andrew M. Scott Feasibility Study: Estimating Radiation Exposure to the Eye Lens Dose Monitors from the Torso Radiation Monitors in Molecular Imaging
Radiation, Safety, Eye Lens
ID04 Nick Wright, Wesley Ng, Sze Ting Lee, Kunthi Pathmaraj, Andrew Scott Regular auditing to optimise Facility Reference Levels and Technologist Radiation Exposure for NM and PET procedures
ID05 Chappell B; Pathmaraj K; Lee ST Incidence of 99mTcMAG3 Hepatic Extra-Renal Excretion Activity in Clinical Renal Scintigraphy
Renal, Nuclear Medicine
ID06 Marney Greenwood, Kunthi Pathmaraj, Sze Ting Lee 99mTc-MAG3 SPECT/CT Diagnosis of Renal Transplantation Leak
ID07 U. Ackermann,A Veamatahau, A.M. Scott Development of Quality Control Method for evaluation of in house production of 18F-Fluoroestradiol (FES) a PET estrogen receptor imaging ligand
ID08 Jason Wong, Michael Galea, David Van Gelderen, Amy Baker, Marcus Cheng, Derek Neoh, Sally Ng
CT angiography protocol for the planning of deep inferior epigastric perforator flap
ID09 Pey Ling Shum, Winston Chong, Hamed Asadi General Anaesthesia vs Non-General Anaesthesia For Endovascular Clot Retrieval In Suspected Or COVID-19 Positive Cases
ID10 Foo M, Maingard J, Hall J, Ren Y, Mitreski G, Slater LA, Chandra R, Chong W, Jhamb A, Russell J, Kok HK, Brooks M, Asadi H
Endovascular Treatment of Intracranial Aneurysms Using the Novel Low Profile Visualized Intraluminal Support EVO
intracranial aneurysms, endovascular
therapy, stent- assisted coiling
Search the pdf for keywords, author name etc ID11 Pey Ling Shum, Hong Kuan Kok, Julian Maingard, Mark Schembri,
Ramon Martin F. Banez, Vivienne Van Damme, Christen D. Barras, Lee- Anne Slater, Winston Chong, Ronil V. Chandra, Ashu Jhamb, Mark Brooks, Hamed Asadi.
Environmental Sustainability in Neurointerventional Procedures: A waste audit
ID12 Daniel Xing, James Korte, Richard Khor, Carlos Cardenas, Houda Bahig, Clifton Fuller and Sweet Ping Ng
Changes in Radiomic Features in Weekly MRI ADC Maps During Radiotherapy in Patients with Head and Neck Cancer
ID13 Dee Zhen Lim, Melissa Yeo, Ariel Dahan, Bahman Tahayori, Hong Kuan Kok, Mohammad Abbasi-Rad, Julian Maingard, Numan Kutaiba, Jeremy Russell, Vincent Thijs, Ashu Jhamb, Ronil V. Chandra, Mark Brooks, Christen Barras, Hamed Asadi
Machine learning-based real time location system to streamline acute stroke endovascular intervention
Machine learning, Real time location system, Stroke, Endovascular intervention
ID14 Varun Sharma, Robert Jones, Graham Starkey, Bao Zhong Wong, M. Lindsay Grayson, Helen Opdam, Rohit D'Costa, Angela Vago, Austin Liver Transplant Perfusionist Group, Laura Mackay, Jaishankar Raman, Claire L Gordon
Australian Donation and Transplantation Biobank -First year of linking organ donation to scientific discovery
Biobank; transplantation; organ donation
ID15 Drewett GP, Copaescu A, Mouhtouris E, Hannan N, James F, Smibert OC, Holmes NE, Trubiano JA
Evolution of the Human Cytokine Response from Acute Illness to Disease Resolution in COVID-19 - Implications for Therapeutic Monitoring and Targets
ID16 Drewett GP, Holmes NE, Trubiano JA, Vogrin S, Feldman J, Rose M Evaluation of COVID-Care - a telemedicine intervention for patients with COVID-19
ID17 Ana Copaescu, Effie Mouhtouris, Sara Vogrin, Fiona James, Kyra Y.L. Chua, Natasha E. Holmes, Abby Douglas, Monica A. Slavin, Heather Cleland, Celia Zubrinich, Ar Kar Aung, Michelle S.Y. Goh, Elizabeth J. Phillips, and Jason A. Trubiano, for Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)
The Role of In Vivo and Ex Vivo Diagnostic Tools in Severe Delayed Immune- Mediated Adverse Antibiotic Drug Reactions
Severe cutaneous adverse reactions (SCARs); Delayed hypersensitivity; T- cell mediated hypersensitivity; Adverse drug reactions (ADRs); Skin testing; Intradermal testing; IFN-g
ResearchFest 2021 ID and Medical Imaging Abstracts
Search the pdf for keywords, author name etc enzyme-linked
immunoSpot assay; Ex vivo diagnostic
1D18 Ana Copaescu, Phuti Choshi, Sarah Pedretti, Effie Mouhtouris, Jonny Peter, Jason A Trubiano
Dose Dependent Antimicrobial Cellular Cytotoxicity - Implications for ex vivo diagnostics
cytotoxicity, delayed hypersensitivity reaction, T cells, INF-y, ELISpot, Lactate Dehydrogenase assay, flow cytometry, drug allergy
ID19 Copaescu A, James F, Mouhtouris E, Vogrin S, Smibert O, Gordon C, Drewett G, Holmes NE, Trubiano JA
The role of Immunological and clinical biomarkers to predict clinical COVID-19 severity and response to therapy - A prospective longitudinal study
SARS-CoV-2, interleukin-6, C- reactive protein, cytokine storm, Staphylococcus aureus bacteraemia, sepsis, acute respiratory distress syndrome
ID20 Gordon CL, Smibert OC, Holmes NE, Chua KYL, Rose M, Drewett G, James F, Mouhtouris E, Nguyen THO, Zhang W, Kedzierski L, Rowntree LC, Chua BY, Caly L, Catton MG, Druce J, Sait M, Seemann T, Sherry NL, Howden BP, Kedzierska K, Kwong JC, Trubiano JA
Defective SARS-CoV-2 immune responses in an immunocompromised individual with prolonged viral replication
ID21 Zhang W, Chua BY, Selva K, Kedzierski L, Ashhurst TM, Boyd DF, Heycroft E, Hensen L, James F, Mouhtouris E, Chua K, Drewett G, Copaescu A, Rowntree LC, Habel JR, Clemens EB, Jia X, Allen L, Mordant FL, Amanat F, Krammer F, King NJC, Nicholson S, Mackay LK, Thomas PG, Chung AW, Kwong JC, Holmes NE, Smibert OC, Nguyen THO, Kedzierska K, Trubiano JA, Gordon CL
Immune responses in the respiratory tract and blood of COVID-19 patients reveal mechanisms of disease severity
ID22 Graeme J O'Keefe, Sylvia J Gong, George Rouvalis, Sam Berlangieri and Andrew Scott
This abstract is not included at the request of the author
PET Quantitation
Search the pdf for keywords, author name etc ID23 Graeme J O'Keefe, Sylvia J Gong, George Rouvalis, Harris Panopoulos,
Artur Cichocki and Andrew Scott This abstract is not included at the request of the author
PET Quantitation
ID24 Sam Digby MBBS, Numan Kutaiba MBChB, MMed ClinEpi, FRANCZR This abstract is not included at the request of the author
ID24 Wendy Zhao, Misha Devchand, Natasha E Holmes This abstract is not included at the request of the author
ID25 Christine Wade, Lisa Hui, Natasha Holmes This abstract is not included at the request of the author
ID26 Chua KYL, Vogrin S, Douglas A, Copaescu A, Bury S, Brusco T, Hall R, Lambros B, Stevenson W, Drewett G, Devchand M, Holmes NE, Trubiano JA
This abstract is not included at the request of the author
antibiotic allergy, penicillin allergy, antimicrobial stewardship, delabeling
Feasibility Study: Estimating Radiation Exposure to the Eye Lens Dose Monitors from the Torso Radiation Monitors in Molecular Imaging Background: The annual eye lens equivalent dose limit for occupational radiation exposure has been reduced in Victoria from 150 to 20 mSv averaged over a 60-month period, implemented via the Radiation Regulations 2017. Although personal radiation monitoring of Hp(10) dose using torso radiation monitors is a common requirement in nuclear medicine departments, eye lens dose monitoring has not been routine. The concerns of the possibility for eye lens doses to exceed the new legislated dose limit may arise. Aims: This study aims to determine the feasibility of estimating the Hp(3) equivalent dose to eye lens using Hp(10) torso dose monitoring results. Methods: A series of experiments were conducted to measure the radiation exposure in Hp(10) using Instadose+TM dosimeters and in Hp(3) using VISIONTM dosimeters containing lithium fluoride TLD chips. In these experiments, both the InstaDose+ and VISION dosimeters were irradiated concurrently using various isotopes with different energy spectrums, including Cs-137, F-18, and Tc-99m. Results: The Hp(10) equivalent doses measured using Instadose+ torso dosimeters were consistently higher than the Hp(3) equivalent dose measurements using VISION eye lens dosimeters. The mean difference between Hp(10) and Hp(3) dose readings was 22.0% with a range from 13.3% to 31.1%. The largest difference of readings was observed with the dosimeters irradiated by F-18 broad-beam exposure, and the smallest difference by Cs-137 narrow-beam exposure mainly due to the collimation embedded on the Cs-137 source used for irradiating these dosimeters. Conclusion: The preliminary results indicate that it is feasible to use the Instadose+ torso dosimeter measurements in our molecular imaging facility as a useful approach to estimate eye lens doses. With departmental Hp(10) doses being well within the annual dose constraint (5 mSv), it is unlikely that eye lens equivalent dose limits will be exceeded if using the same level of radiation protection as it for the whole body.
Nick Wright1, Wesley Ng1, Sze Ting Lee1,2,3, Kunthi Pathmaraj1,2, Andrew M
Scott A1,2,3,4
Regular auditing to optimise Facility Reference Levels and Technologist Radiation Exposure for NM and PET procedures 1 Department of Molecular Imaging and Therapy, Austin Health, Heidelberg Victoria, Australia 2 Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia 3 School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia 4 Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
Background - Best practice of nuclear medicine involves obtaining quality diagnostic images whilst minimising dose to both patient and staff, which can be challenging in departments which perform a large volume of procedures. Aim: To review facility reference levels (FRL) at Austin Health, against diagnostic reference levels (DRL) recommended by ARPANSA, with a view to ensure administered radioactivity is within prescribed DRL yet maintain optimal image quality. Methods: Administered radioactivity for NM and PET procedures was collected for 20 patients in two consecutive years. Microsoft Excel template from ARPANSA was utilized to log, graph results, and compare FRL to corresponding ARPANSA DRLs. Results/Discussion: Both the 2017/18 and 2019/20 audits demonstrated excellent compliance to the DRL’s set by ARPANSA. The 2017/18 audit highlighted just one study (renal GFR) exceeded the recommended DRL by 18%. We reduced injected activity by 20% whilst at the same time maintaining accuracy of the GFR computation. The 2019/20 audit results showed that all our diagnostic procedures were well within the prescribed ARPANSA DRLs. Comparing the audits of technologists’ trunk exposure over a 6-month period, the 2019/20 period saw a 7.6% increase in scans performed over the 2017/18 period. Despite this throughput increase, average technologist trunk exposure over the 6- month period remained the same as in 2017/18 (Table 1). This was calculated by averaging the dose readings of 4 technologists who rotated through all areas of the department, during both 6-month periods. Table 1. DRL audit results
% Protocols under ARPANSA DRL
No. patients Average technologist trunk exposure
2017/18 Audit 94.4% 3023 .893 mSv
2019/20 Audit 100% 3254 .890 mSv Note. Number patients scanned only reflect PET procedures, as nuclear medicine procedures were affected by Tc-99m shortages.
Conclusion: Regular auditing and optimising radioactivity administered to patients, together with state-of-the-art imaging hardware and software, excellent image quality and patient throughput can be maintained whilst minimising the radiation exposure to the technologist.
Incidence of 99mTcMAG3 Hepatic Extra-Renal Excretion Activity in Clinical Renal Scintigraphy
Background: 99m
Technetium-Mercaptoacetyltriglycine( 99m
Tc-MAG3) is the radiopharmaceutical of choice
for most renal scintigraphy indications. Compared to other renal agents, 99m
Tc-MAG3’s high renal
extraction rate allows for improved image quality and quantitative assessment of kidney perfusion and
function
99m Tc-MAG3 is primarily cleared by renal tubular secretion (>90%) but also hepatic excretion, resulting in
normal physiological uptake within liver, gallbladder, and subsequent gut activity. Reported biliary
excretion varies in literature from 2%-10% in normal and patient populations. A recent clinical study
demonstrated gallbladder or small bowel activity in 23% of patients following frusemide administration for
evaluation of urinary obstruction.
Tc-MAG3 hepatobiliary extra-renal excretion activity-(HEEA) in
routine renal scintigraphy, determine the impact on image interpretation and identify causal factors.
Method: A retrospective review of all clinical 99m
Tc-MAG3 renal studies performed from January 2020-
2021 was performed. Studies were suitable for HEEA assessment if the liver and gallbladder were within
the field of view. Early dynamic, lateral and post-micturition static and, where available, post-diuretic
imaging were visually assessed for HEEA: presence, location, and time of appearance. Statistical
analysis was performed, and the HEEA incidence rate calculated. Possible causal factors:
radiopharmaceutical purity, frusemide administration and impaired renal or liver function were also
investigated.
Tc-MAG3 renal studies performed were available for HEEA analysis. HEEA
was present in 22%(95%CI=15.4-29.1), (n=33), of studies with an incidence rate of 21.71 cases/100
studies. In 91%(n=30) of positive studies, HEEA was confined to the gall bladder, and was only
discernible on lateral planar imaging in 76.7%. Additional SPECT/CT was performed in 9.1%(n=2) of
HEEA positive studies to assist with image interpretation. 8.6%(n=6) of post-diuretic studies were HEEA
positive. No causal factors for HEEA were identified.
Conclusion: 99m
Tc-MAG3 HEEA appears more common than reported in the literature and should be
considered during renal image interpretation.
99mTc-MAG3 Diagnosis of Renal Transplantation Leak
Case Description:
A 32-year-old male with end stage renal failure on background of Focal Segmental Glomerulosclerosis secondary to Anti-Phospholipid Syndrome was referred for a day 1 post-cadaveric renal transplant MAG3 scan to investigate for possible surgical complications.
Procedures Performed:
The patient underwent routine day 1 post-transplant ultrasound which was reported as visualising intraperitoneal fluid, likely post-surgical free fluid. A 99mTc-MAG3 Renal Study with SPECT/CT was subsequently performed to evaluate transplant perfusion and function. Dynamic imaging commenced immediately post injection of 211MBq of 99mTc-MAG3. Dynamic images were ceased prematurely at 10 minutes, due to pain at the site of transurethral catheter insertion. SPECT/CT imaging commenced once patient had pain relief.
Findings:
The MAG3 scan appearances was reported as typical appearance of acute tubular necrosis day 1 post- transplant and absence of excretion into urinary bladder was noted. However, there was extra-renal activity demonstrated inferior to the lower renal pole, anterior to the rectum, which localized to the distal ureter on the SPECT/CT images, raising the possibility of a urinary leak into the peritoneal space.
Outcome:
The patient returned to surgery for re-implantation of ureter anastomosis avulsion, where 3L of fluid/urine was drained from the peritoneal cavity and a surgical drain inserted. Follow-up ultrasound imaging confirms patency of the renal transplant and the patient is now producing urine and progressing as expected 3-months post-transplant.
Discussion:
The urine leak diagnosed on the 99mTc-MAG3 SPECT/CT study was unable to be detected through ultrasound imaging. Leak of urine into peritoneal space was due to the ureteric anastomosis avulsion, which was found during surgery. This pertinent finding on the 99mTc-MAG3 study and use of SPECT/CT significantly altered the management for this patient which led to surgical revision and overall success of the renal transplant.
Development of Quality Control Method for evaluation of in house production of 18F-Fluoroestradiol (FES) a PET estrogen receptor imaging ligand Background: The accurate assessment of the estrogen receptor (ER) level of tumors at diagnosis can improve response to appropriate hormone therapies. 18F-Fluoroestradiol has a high affinity to ER in-vivo which makes it a safe and effective positron emission tomography (PET) imaging agent for the investigation of tumor ER activity. Aims: Develop and optimize quality control method to evaluate the in house radiosynthesis of 18F-FES for human clinical trial. Methods: A reverse-phase gradient method was developed on a Shimadzu Prominence HPLC system with LabLogic Flow Ram radio-HPLC detector for radiation detection, using Shimadzu Labsolution software for analysis. Phenomenex Luna 5 micron C18 (250 x 4.6mm) analytical column was used as stationary phase with water (A) and acetonitrile (B) as mobile phase at a flow rate of 1.2mL/min with gradient elution for analysis over 25 minutes: 0-15 minutes (40%B), 15-17 minutes (40%B to 90%B), 17-25 minutes (90%B). UV detector wavelength set at 280 nm. A TLC method with Silica gel glass fiber strip as stationary phase develop in 95% acetonitrile and 5% water was also used to quantify free 18 F-fluoride. Residue kryptofix test resulted in < 50 µg/mL. Standard curve of FES was produced with serial dilution method to determine minimum detectable limit of the system and specific activity calculation. Results: Good baseline separation was achieved with FES standard (retention time of 13 minutes) and other radiochemical impurities produced during radiosynthesis. From the validation tests (n=3) an average radiochemical purity of > 99% was achieved with both HPLC and TLC, an average total chemical impurity and specific activity being 0.29 µg/mL and 1.88 Ci/µmol (69.59 GBq/ µmol) respectively. Conclusion: Quality control method has been developed for the analysis of 18F-FES; the compound will be introduced in human clinical trial in our department later in the year.
Jason Wong2, Michael Galea2, David Van Gelderen2, Amy Baker2, Marcus Cheng1, Derek Neoh1, Sally Ng1 ¶ Computed tomographic angiography Protocol for the planning of deep inferior epigastric perforator flap
1. Department of Plastic Surgery, Austin Health, Heidelberg, Vic., Australia; 2. Department of Radiology, Austin Health, Heidelberg, Vic., Australia; Aim The Deep Inferior Epigastric Perforator (DIEP) flap is the main choice in autologous breast reconstruction. The DIEP flap involves transferring the patient’s own abdominal skin and subcutaneous tissue from the lower abdomen to the chest wall to form a new breast mould, and requires careful intramuscular dissection of the perforators that supply the tissue to be transferred, whilst preserving the rectus abdominus muscle. Preoperative Computed Tomographic Angiography (CTA) effectively maps these perforators for the planning of the DIEP flap. Methods Patients undergo abdominal CTA imaging as part of surgical planning. The IV contrast enhanced scan is performed using specific scanning parameters and image reconstruction methods developed at Austin Radiology. A CT marker is placed at the patient’s umbilicus and abdominal DIEA perforators are identified with location coordinates relative to the umbilical marker by experienced radiologists. Calibre and course of each perforator are also described. Results CTA is able to accurately identify the DIEA perforators and trace their course, as well as allow assessment of specific characteristics to determine their suitability to sustain the DIEP flap. The CTA findings have already assisted in the planning of multiple Austin patients requiring DIEP flap breast reconstruction. Conclusion Pre-operative CTA is crucial in the planning of the DIEP flap as it reveals the anatomy and improves surgical efficiency and ultimately patient safety. Protocoling the CTA in a standardised fashion allows radiologists to help the surgical team to identify the best perforators for the purpose of planning a DIEP flap.
References Buntic, R., 2020. The Deep Inferior Epigastric Artery Perforator (DIEP) Flap. [online] microsurgeon.org. Available at: <https://www.microsurgeon.org/diep> [Accessed 2 September 2020]. Karunanithy, N, Rose, V, Lim, AKP & Mitchell, A 2011, “CT Angiography of Inferior Epigastric and Gluteal Perforating Arteries before Free Flap Breast Reconstruction,” RadioGraphics, vol. 31, no. 5, pp. 1307–1319. Phillips, TJ, Stella, DL, Rozen, WM, Ashton, M & Taylor, GI 2008, “Abdominal Wall CT Angiography: A Detailed Account of a Newly Established Preoperative Imaging Technique,” Radiology, vol. 249, no. 1, pp. 32–44.
Pey Ling Shum1, Winston Chong2,3, Hamed Asadi2,4,5,6
General Anaesthesia vs Non-General Anaesthesia For Endovascular Clot Retrieval In Suspected Or COVID-19 Positive Cases
1. Monash Health, Clayton, Victoria, Australia; 2. Interventional Neuroradiology Unit, Monash Imaging, Monash Health, Clayton, Victoria,
Australia; 3. Department of Imaging, Monash University, Clayton, Victoria, Australia; 4. School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia; 5. Interventional Neuroradiology Service, Department of Radiology, Austin Health, Heidelberg,
Victoria, Australia; 6. Florey Institute of Neuroscience and Mental Health - Austin Campus, Stroke Division,
Heidelberg, Victoria, Australia.
Aim Prior to COVID-19 pandemic, the choice of anaesthetic approach for Endovascular Clot Retrieval (ECR), whether general anaesthesia (GA) or non-GA, remains controversial. With the emergence of COVID-19 pandemic, the Society for Neuroscience in Anesthesiology & Critical Care, the Society of NeuroInterventional Surgery and the Society of Vascular and Interventional Neurology have published their own recommendations. We aimed to investigate how hospital practice in Australia and New Zealand changes regarding ECR and anaesthetic approach during the COVID-19 pandemic. Methods We emailed INRs from 11 ECR sites in Australia and New Zealand to investigate 1) INRs preference for anaesthetic approach during ECR on suspected or positive COVID-19 patients, 2) INRs usual practice prior to COVID-19 pandemic and whether COVID-19 pandemic has precipitated a change in practice, 3) Incidence of stroke most likely caused by COVID-19. Results We found that three hospitals that were performing ECR mainly under CS or non-GA pre- COVID pandemic, adopted GA for all or majority of ECR cases or have a very low threshold for GA during the pandemic. The other seven hospitals were already performing the majority or all their ECR under GA pre-COVID pandemic; one hospital did not change practice and continue to perform ECR under CS or non-GA if patient is co-operative. Among all the ECR sites surveyed, there were no confirmed cases of stroke caused by COVID-19 reported among INRs. Conclusion In conclusion, the COVID-19 pandemic has changed anaesthetic practice for ECR cases, mainly favouring GA. Further research is necessary to investigate the effect of performing ECR under GA amidst the COVID-19 pandemic, risk of ischemic stroke with COVID-19 infection, risk of transmission and protection strategies for INRs, ways to optimise workflow and minimise delay in door to reperfusion time.
Endovascular Treatment of Intracranial Aneurysms
Using the Novel Low Profile Visualized Intraluminal
Support EVO Stent: Multicenter Early Feasibility
Experience
Foo M, Maingard J, Hall J, Ren Y, Mitreski G, Slater LA, Chandra R, Chong W, Jhamb A, Russell J, Kok
HK, Brooks M, Asadi H
Purpose: Low-profile, self-expandable stents have broadened therapeutic options available for definitive
treatment of intracranial aneurysms. The novel Low-Profile Visualized Intraluminal Support (LVIS) EVO stent
extends upon the success of its predecessor, the LVIS Jr stent, aiming to enable higher visibility and greater
opening ability within a self-expandable and fully retrievable microstent system. In this study, we aim to report
the early safety and feasibility experience with the LVIS EVO stent.
Materials and Methods: A multicenter, retrospective, observational study was conducted on patients who had
intracranial aneurysms treated with the LVIS EVO stent across 3 Australian neurovascular centers between
February 2020 and September 2020. Short-term technical and clinical outcomes were evaluated.
Results: A total of 22 LVIS EVO stents were successfully implanted to treat 15 aneurysms (3 ruptured, 12
unruptured) in 15 patients. Aneurysms ranged from 2 mm to 35 mm in dome height. The LVIS EVO stent was
used for stent-assisted coiling in 11 patients and flow diversion in 4 patients. There were no device-related
procedural complications. There were 2 cases of peri-procedural symptomatic thromboembolic complications
and no procedure-related mortality. At early radiological follow up, 10 patients had complete occlusion, 4
patients had small neck remnants, and 1 patient who was managed with flow diversion had a residual aneurysm
as expected.
Conclusion: Early experience with the LVIS EVO stent demonstrated safety and feasibility for stent-assisted
coiling as well as flow diversion for intracranial aneurysms. In this heterogeneous cohort, including ruptured,
complex, and large aneurysms, all cases were technically successful.
Pey Ling Shum1, Hong Kuan Kok2,3, Julian Maingard3,4, Mark Schembri5, Ramon Martin F. Banez4, Vivienne Van Damme5, Christen D. Barras6,7, Lee-Anne Slater4, Winston Chong4, Ronil V. Chandra4, Ashu Jhamb8, Mark Brooks5,9, Hamed Asadi3,4,5,9 Environmental Sustainability in Neurointerventional Procedures: A waste audit 1. Department of Neurosurgery, Monash Health, Clayton, Victoria, Australia; 2. Interventional Radiology Service, Department of Radiology, Northern Health,
Epping, Victoria, Australia; 3. School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria,
Australia; 4. Interventional Neuroradiology Unit, Monash Imaging, Monash Health, Clayton,
Victoria, Australia; 5. Interventional Neuroradiology Service, Department of Radiology, Austin Health,
Heidelberg, Victoria, Australia; 6. South Australian Health and Medical Research Institute, Adelaide, South Australia,
Australia; 7. Department of Radiology, Royal Adelaide Hospital, Adelaide, South Australia,
Australia; 8. Interventional Radiology Service, Department of Radiology, St. Vincent's Hospital,
Fitzroy, Victoria, Australia; 9. Florey Institute of Neuroscience and Mental Health - Austin Campus, Stroke
Division, Heidelberg, Victoria, Australia. Aim Operating rooms contribute between 20-70% of hospital waste. This study aimed to evaluate the waste burden of neurointerventional procedures performed in a Radiology department, identify areas for waste reduction, and motivate new greening initiatives. Methods We performed a waste audit of 17 neurointerventional procedures at a tertiary-referral center over a 3-month period. Waste was categorized into five streams: general waste, clinical waste, recyclable plastic, recyclable paper, and sharps. Our radiology department started recycling soft plastics from 13 December 2019. Hence, an additional recyclable soft plastic waste stream was added from this time point. The weight of each waste stream was measured using a digital weighing scale. Results We measured the waste from seven cerebral digital subtraction angiograms (DSA), six endovascular clot retrievals (ECR), two aneurysm coiling procedures, one coiling with tumour embolisation and one dural arteriovenous fistula embolisation procedure. In total, the 17 procedures generated 135.3 kg of waste: 85.5 kg (63.2%) clinical waste, 28.0 kg (20.7%) general waste, 14.7 kg (10.9%) recyclable paper, 3.5 kg (2.6%) recyclable plastic, 2.2 kg (1.6%) recyclable soft plastic, and 1.4 kg (1.0%) of sharps. An average of 8.0 kg of waste was generated per case. Coiling cases produced the
greatest waste burden (13.1 kg), followed by embolisation (10.3 kg), ECR (8.8 kg) and DSA procedures (5.1 kg). Conclusion Neurointerventional procedures generate a substantial amount of waste, an average of 8kg per case. Targeted initiatives such as engaging with suppliers to revise procedure packs and reduce packaging, digitising paper instructions, opening devices only when necessary, implementing additional recycling programs and appropriate waste segregation have the potential to reduce the environmental impact of our speciality.
Figure 1: User manuals and packaging from one coiling with tumour embolisation case.
The weight of the pile of user manuals (on the left) amounted to 2.6 kg and the
packaging (on the right) weighed 2.7 kg.
Figure 2: Waste collected from one aneurysm coiling procedure. From left to right:
recycling bin (including paper, cardboard and hard plastic), two bags of clinical waste
and one bag of general waste.
Figure 3: Soft plastics recycling bin
Daniel Xing1, James Korte2, Richard Khor1, Carlos Cardenas3, Houda Bahig4, Clifton Fuller3 and Sweet Ping Ng1 ¶ Changes in Radiomic Features in Weekly MRI ADC Maps During Radiotherapy in Patients with Head and Neck Cancer
1 Oliver Newton-John Cancer Wellness & Research Centre, Austin Health, Melbourne, AUSTRALIA 2 Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA 4 Department of Radiation Oncology, Centre Hospitalier de I’Universite de Montreal, CANADA
Aim Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumours, which may be captured by a variety of quantitative features derived from diagnostic imaging, termed radiomics. The aim of this study is to evaluate the MRI-based tumour radiomic features during curative intent (chemo)radiotherapy in HNSCC patients so as to identify the radiomic features which change in response to treatment. ¶
Methods A single institution prospective cohort of patients with squamous cell carcinoma (SCC) of head and neck mucosa, who underwent curative intent (chemo)radiotherapy. The study collected pretreatment MRI images, weekly serial MR imaging during RT and post treatment MRI images. The target volume delineations were performed on specified sequences. Six categories of MRI ADC radiomic features (i.e. Shape, Gray-level run length, Gray-level co- occurence, Neighborhood grey-tone difference, Gradient orient histogram and Intensity direct) and a total of 122 radiomic features were derived from the primary tumour using IBEX software. The absolute values of these features are plotted over time and the trends if these values were observed. ¶
Results Fifty-two patient were enrolled in this study. For Gray-level run length analysis, High gray level run emphasis (median 3,858 vs. 5,744; pre-treatment vs. post- treatment) and Short run high gray level emphasis (median 3,431 vs. 5,273) has the tendency to increase over time during treatment. For the Gray-level co- occurence analysis, Auto correlation (median 3,816 vs. 5,908) and Sum variance (median 13,907 vs. 22,005) consistently increased, while Max probability (median 0.15 vs. 0.10) decreased over time. For Neighborhood grey- tone difference, there was a trend of increase in value of Complexity (median 2,962,617 vs. 7,953,246; pre-treatment vs. post-treatment) and Texture Strength (median 483 vs. 966). Multiple values of Intensity direct had the trend of increasing. ¶
Conclusion This study describes the primary tumour MRI ADC map radiomic change during (chemo)radiotherapy for HNCC. Further studies in a larger cohort are
required to validate these kinetics and their potential utility to assess patient treatment response during radiotherapy.
Dee Zhen Lim 1, Melissa Yeo 2, Ariel Dahan 1, Bahman Tahayori 3, Hong Kuan Kok 4,5, Mohammad Abbasi-Rad, Julian Maingard 7,8, Numan Kutaiba 1, Jeremy Russell 9, Vincent Thijs 10,11, Ashu Jhamb 12, Ronil V. Chandra 7,8, Mark Brooks 1,5, Christen Barras 13,14, Hamed Asadi 1,5
Machine learning-based real time location system to streamline acute stroke endovascular intervention 1 Department of Radiology, Austin Hospital, Heidelberg, Victoria, Australia 2 School of Medicine, University of Melbourne, Melbourne, Victoria, Australia 3 Department of Biomedical Engineering, The University of Melbourne, Melbourne, Victoria, Australia 4 Department of Radiology, Northern Health, Epping, Victoria, Australia 5 School of Medicine, Faculty of Health, Deakin University, Burwood, Victoria, Australia 7 Department of Radiology, Monash Health, Clayton, Victoria, Australia 8 Faculty of Medicine Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia 9 Department of Neurosurgery, Austin Hospital, Heidelberg, Victoria, Australia 10 Department of Neurology, Austin Health, Heidelberg, Victoria, Australia 11 Stroke Theme, Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia 12 Department of Radiology, St Vincent’s Hospital, Fitzroy, Victoria, Australia 13 South Australian Institute of Health and Medical Research, Adelaide, South Australia, Australia 14 School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia Aim: Delivery of endovascular clot retrieval (ECR) in acute stroke requires complex coordination of the patient and many stroke team members across different locations in the hospital. Not knowing each individual’s location throughout the progress of a stroke call can cause miscommunication and inefficiencies in the delivery of ECR. 1 Machine learning (ML) can be used to develop a real time location system (RTLS) based on existing hospital WiFi. 2,
3 This is called WiFi fingerprinting (see Figure 1). We propose a WiFi fingerprinting model of RTLS to streamline delivery of ECR. Methods: In this proof-of-concept study, an investigator collected WiFi data from different hospital zones at Austin Hospital. Hospital zones relevant to the ECR workflow such as the emergency department, computed tomography scanner, angiography suite, intensive care units and stroke ward were included. The WiFi data were split into training (location-labelled) and testing (location- unlabeled) dataset. ML algorithms such as K nearest neighbors, decision tree, random forest, support vector machine and 2-ensemble models were trained with the labelled WiFi data. The same ML algorithms were then used to predict the investigator’s location with the unlabeled WiFi data. The accuracies of the different ML algorithms, in percentage of correct hospital zones prediction, were measured.
Results: ML algorithms can accurately predict the investigator’s location, to the precision of hospital zones relevant to the ECR workflow. The ML algorithms with the maximal accuracy (98.0%) were random forest and support vector machine models. Other ML algorithms such as ensemble models, K nearest neighbors and decision tree also achieved accuracy of 97.0%, 97.0% and 96.0% respectively. Conclusion: WiFi fingerprinting, a machine learning-based real time location system, has the potential to streamline delivery of acute stroke endovascular intervention by efficiently tracking patient and staff movement during a stroke call. References:
1. Prater A, Bowen M, Pavich E, Hawkins CM, Safdar N, Fountain J, et al. Enhancing Workflow Analysis in Acute Stroke Patients Using Radiofrequency Identification and Infrared-based Real-Time Location Systems. J Am Coll Radiol. 2017;14(2):231-4.
2. Xia S, Liu Y, Yuan G, Zhu M, Wang Z. Indoor fingerprint positioning based on Wi-Fi: An overview. ISPRS International Journal of Geo-Information. 2017;6(5):135.
3. Kamel Boulos MN, Berry G. Real-time locating systems (RTLS) in healthcare: a condensed primer. Int J Health Geogr. 2012;11:25.
Word count: 289 words
Figure 1: The basis of WiFi fingerprinting is that WiFi signal strength at different hospital location is different. As the patient move from the emergency department to the CT machine room, the signal strength profile (also called a fingerprint) changes. Machine learning algorithms can be trained to predict locations using the unique signal strength profile. AP: wireless Access Point, CT: computed tomography.
Australian Donation and Transplantation Biobank – First year of linking organ donation to scientific discovery
Varun Sharma1,2, Robert Jones1,2, Graham Starkey1, Bao Zhong Wong1,2,M. Lindsay Grayson1,7, Helen Opdam1,6, Rohit D’Costa3,4, Angela Vago1, Austin Liver Transplant
Perfusionist Group1, Laura Mackay5, Jaishankar Raman1,2, Claire L Gordon1,5
1) Austin Health, Heidelberg, Melbourne, Australia 2) Department of Surgery, University of Melbourne, Austin Health, Heidelberg,
Melbourne, Australia 3) DonateLife Victoria, Melbourne, Australia 4) Melbourne Health, Parkville, Melbourne, Australia 5) Department of Microbiology and Immunology, Peter Doherty Institute for Infection
and Immunity, University of Melbourne, Melbourne, Australia 6) Organ and Tissue Authority, Canberra, Australia 7) Department of Medicine, University of Melbourne, Austin Health, Heidelberg,
Melbourne, Australia
Purpose Human tissues are crucial for translating discoveries from animal models to humans, however access to tissue is challenging. We report the feasibility of an organ donor tissue resource, the Australian Donation and Transplantation Tissue Bank (ADTB), in overcoming this barrier.
Methodology The ADTB is a collaboration between, Austin Health, DonateLife Victoria and the University of Melbourne. Study consent from donor families was obtained by Donation Specialist Nursing Coordinators and tissues were sampled by the Austin retrieval team during the donation operation. Blood and multiple lymphoid, visceral and mucosal tissue sites were collected. Tissues were transported to the Austin and sent directly to the researcher or stored for future research. Relevant donor information is collected and stored in a secure database.
Results Over a 21 month period, tissues were sampled from 60 donors, 40 (67%) of which were donation-after-brain-death and the remainder donation-after-circulatory-death. The mean donor age was 47±25 years. Causes of death included anoxia (13, 22%), cerebrovascular events (35, 58%), trauma (7, 12%), and other (2, 3%). A mean of 8±3 tissue sites were sampled per donor: blood (50, 83%), lung (26, 43%), liver (19, 32%), skin (49, 82%), duodenum (48, 80%), ileum (49, 54%), colon (49, 82%), spleen (52, 87%) and bone marrow (50, 83%). To date, donor tissue has been used in eleven research projects and has already contributed to two scientific publications currently under review.
Conclusions
The ADTB has successfully provided human tissue for numerous scientific projects, demonstrating the feasibility and potential of linking organ donation to translational human tissue-based research.
Evolution of the Human Cytokine Response from Acute Illness to Disease Resolution in COVID-19 – Implications for Therapeutic Monitoring and Targets
Authors:
Drewett GP 1,2 , Copaescu A 2,3 , Mouhtouris E 1,2 , Hannan N 4 , James F 1,2 , Smibert OC 1 , Holmes NE 1,2,5,8 , Trubiano JA 1,2,5,6,7
1. Department of Infectious Diseases, Austin Health, Heidelberg, Australia 2. Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia 3. Clinical Immunology and Allergy, McGill University Health Center, Montréal, Canada 4. Therapeutics Discovery and Vascular Function Laboratory, Translational Obstetrics Group, Department of Obstetrics & Gynaecology, The University of Melbourne 5. Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Australia 6. Department of Oncology, Sir Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia 7. The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia 8. Department of Medicine and Radiology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia
Category: COVID-19
Introduction: The role of cytokines in COVID-19 as markers of disease severity, in monitoring response to therapy, and as potential targets for therapeutic intervention remains ill defined. We analysed a prospective COVID-19 cohort with timed patient sampling to explore longitudinal comprehensive cytokine responses from hospital admission to discharge.
Methods: We performed a prospective observational cohort study of adult patients admitted with COVID-19 between May and October 2020 at Austin Health, Melbourne. Cytokine analysis was performed on plasma using a multiplex bead array kit 17-plex panel (BioPlex Pro Human cytokine GrpI Panel, Bio-Rad), and read using the BioPlex 200 instrument (Bio-Rad).
Results: 71 participants had admission plasma analysed, 35 (49%) with paired plasma at discharge included in this analysis. 63% patients received corticosteroid therapy, 49% required supplementary oxygen, and 31% patients required intensive care unit (ICU) admission. From admission to discharge, a significant decrease in interleukin-6 (p <0.001), tumour necrosis factor alpha (TNF-a) (p=0.002), monocyte chemoattractant protein-1 (MCP-1) (p= 0.02) and IL-1b (p=0.03) was observed. Detectable levels of IL-7, IL-8, and IL-10 were found, without significant decrease noted from admission to discharge. Levels of IL-2, IL-5, IL-12, IL-13, IL- 17, granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor were not elevated at either timepoint.
Conclusion: We found an elevation in several potentially clinically significant cytokines, and a significant reduction in IL-6, TNF-a, IL-1b and MCP-1 associated with disease convalescence, demonstrating the immunopathological importance of these cytokines in COVID-19 and future pathways for disease modulation.
Disclosure of Interest Statement: Study supported by Austin Health Fundraising. No competing interests declared.
Evaluation of COVID-Care – a telemedicine intervention for patients with COVID-19
Authors: Drewett GP 1, Holmes NE 1,2, Trubiano JA 1,3, Vogrin S 3, Feldman J 4, Rose M 1
1. Department of Infectious Diseases, Austin Health, Victoria, Australia 2. Department of Critical Care, The University of Melbourne, Victoria, Australia; Data Analytics Research and Evaluation (DARE) Centre, Austin Health and The University of Melbourne, Victoria, Australia 3. Department of Medicine, University of Melbourne, Victoria, Australia 4. Arden Street Labs, Melbourne, Australia
Category: Poster/Oral Presentation
Introduction: The COVID-19 pandemic and restrictions placed on movement to prevent its transmission has led to a surge in demand for remote medical care. We investigated whether COVID- Care, a patient-reported telehealth symptom monitoring system, was successful at delivering safe monitoring and care for these patients leading to decreased hospital presentations.
Methods: We performed a single centre, prospective, interventional cohort study with symptomatic outpatients who presented for COVID-19 screening at Austin Health, Australia. Participants were invited to take part in the COVID-Care program, entering common COVID-19 symptoms on a purpose-built, online survey monitored by infectious diseases physicians, and matched with clinical data including date of symptom onset, hospital admission, and screening clinic presentations.
Results: 42,158 COVID-19 swabs were performed in 31,626 patients from March to October 2020, with 414 positive cases. 20,768 people used the COVID-Care survey at least once. COVID- Care users were significantly younger than non-users. Of the 414 positive cases, 254 used COVID-Care, with 160 non-users. Excluding presentations on the same day or prior to the COVID-19 swab, there were 56 hospital presentations. 4.3% of COVID-Care users and 28.1% non-users were admitted to hospital or the Emergency Department (p<0.001), with 3.9% vs 22.5% requiring inpatient admission (p<0.001). There were no deaths in COVID- Care users vs 2 deaths in non-users.
Conclusion: COVID-Care, a digitally integrated, outpatient, symptom tracking and telemedical service for patients with COVID-19, was safe and successful at reducing hospital and emergency department admissions, suggesting a strong role for telemedicine for future healthcare delivery in this logistically challenging setting.
Disclosure of Interest Statement: No specific funding received. No competing interests to declare.
The Role of In Vivo and Ex Vivo Diagnostic Tools in
Severe Delayed Immune-Mediated Adverse
Ana Copaescu, MD, FRCPCa,b, Effie Mouhtouris, BSca, Sara Vogrin, MBBS, MBiostatc, Fiona James,
BBiomedScia,Kyra Y.L. Chua, MBBS, FRACP, FRCPA, PhDa, Natasha E. Holmes, MBBS, FRACP, PhDa,d,
Abby Douglas, MBBS, FRACPe,f,g, Monica A. Slavin, MBBS, FRACPe,f,g, Heather Cleland, MMBSh,
Celia Zubrinich, MBBSi,j, Ar Kar Aung, MBBS, FRACP, MPHTMk, Michelle S.Y. Goh, MBBS, FACDl,m,n,
Elizabeth J. Phillips, MD, FRCPC, FRACPo,p, and Jason A. Trubiano, MBBS, BBiomedSci, FRACP, PhDa,f,g,q; for
Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR) aCentre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia bClinical Immunology and Allergy, McGill University Health Center, Montr al, QC, Canada
cDepartment of Medicine, St Vincent’s Hospital, University of Melbourne, Fitzroy, VIC, Australia dDepartment of Medicine and Radiology, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia
eDepartment of Infectious Diseases and Infection Prevention, Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, VIC, Australia fThe National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
gDepartment of Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, VIC, Australia hBurns Unit, Alfred Health, Melbourne, VIC, Australia
iAllergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, VIC, Australia jSchool of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
kDepartment of General Medicine, Alfred Health, Melbourne, VIC, Australia lDepartment of Dermatology, Austin Health, Heidelberg, VIC, Australia
mDepartment of Dermatology, Alfred Health, Melbourne, VIC, Australia nDepartment of Dermatology, St Vincent’s Hospital, Fitzroy, VIC, Australia
oInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia pDepartment of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, Tenn
qDepartment of Medicine (Austin Health), The University of Melbourne, Heidelberg, VIC, Australia
BACKGROUND: The use of in vivo and ex vivo diagnostic tools for delayed immune-mediated adverse drug
reactions is currently ill defined.
OBJECTIVE: To determine whether the combination of skin testing and/or IFN-g enzyme-linked immunoSpot
assay (ELISpot) can aid diagnosis of these allergy phenotypes.
METHODS: Patients with antibiotic-associated severe delayed immune-mediated adverse drug reaction
hypersensitivity, including Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with
eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis, generalized bullous
fixed drug eruption, and severe maculopapular exanthema, were prospectively recruited. In vivo testing was
completed to the implicated drug(s), and ex vivo testing was performed with the patient’s PBMCs stimulated
with the relevant antibiotic concentrations for IFN-g release ELISpot measurement.
RESULTS: Eighty-one patients met the inclusion criteria, with DRESS (42; 51.9%) accounting for most cases.
Among the 63 (78%) who had an ELISpot assay performed, 34 (54%) were positive to at least 1 implicated
antibiotic (median spot-forming units/million cells, 99.5; interquartile range, 68-187), with glycopeptide being
a strong predictor of positivity (adjusted odds ratio, 6.11; 95% CI, 1.74-21.42). In combination (in vivo and ex
vivo), 51 (63%) of those tested were positive to an implicated antibiotic. For DRESS and severe maculopapular
exanthema associated with penicillins and cephalosporins, this combination confirmed the culprit agent in 11 of
the 12 cases and in 6 of 7 for DRESS associated with glycopeptides.
CONCLUSIONS: This study demonstrates that using in vivo in combination with ex vivo testing can enhance
the diagnostic approach in these severe phenotypes by assisting with the identification of possible culprit
antibiotics.
Dose Dependent Antimicrobial Cellular Cytotoxicity – Implications for ex vivo
diagnostics
Trubiano1,4,5,6
*Co-first authors **Co-Senior authors 1Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia 2Allergy and Immunology Unit, University of Cape Town Lung Institute, South Africa 3Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, South Africa 4Department of Oncology, Sir Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia 5Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Australia 6The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
INTRODUCTION Ex vivo and in vitro diagnostics, such as interferon- (IFN-) release enzyme linked
ImmunoSpot (ELISpot) and flow cytometry, are increasingly employed in the research and diagnostic
setting for severe T-cell mediated hypersensitivity. Despite an increasing use of IFN- release ELISpot for
drug causality assessment and utilization of a range of antimicrobial concentrations ex vivo, data regarding
antimicrobial-associated cellular cytotoxicity and implications for assay performance remain scarcely
described in the literature. Using the measurement of lactate dehydrogenase (LDH) and the 7-AAD cell
viability staining, we aimed, via an exploratory study, to determine the maximal antimicrobial
concentrations required to preserve cell viability for commonly implicated antimicrobials in severe T-cell
mediated hypersensitivity.
METHOD After an 18-hour incubation of patient peripheral blood monocytes (PBMCs) and antimicrobials
at varying drug concentrations, the cell cytotoxicity was measured in two ways. A colorimetric based assay
that detects LDH activity and by flow cytometry using the 7-AAD cell viability staining. We used the
PBMCs collected from three healthy control participants with no known history of adverse drug reaction
and two patients with a rifampicin-associated drug reaction with eosinophilia and systemic symptoms
(DRESS), confirmed on IFN- ELISpot assay. The PBMCs were stimulated for the investigated drugs at
the previously published drug maximum concentration (Cmax), and concentrations 10- and 100-fold above.
RESULTS In an HIV negative and positive rifampicin-associated DRESS with positive ex vivo IFN-
ELISpot assay, use of 10- and 100-fold Cmax drug concentrations decreased spot forming units/million
cells by 32-100%, and this corresponded to cell cytotoxicity of more than 40% and 20% using an LDH
assay and 7-AAD cell viability staining, respectively. The other antimicrobials (ceftriaxone, flucloxacillin,
piperacillin/tazobactam and isoniazid) tested in healthy controls showed similar dose-dependent increased
cytotoxicity using the LDH assay, but cytotoxicity remained lower than 40% for all Cmax and 10-fold
Cmax drug concentrations except flucloxacillin. All 100-fold Cmax concentrations resulted in cell death >
40% (median 57%), except for isoniazid. 7-AAD cell viability staining also confirmed an increase in
lymphocyte death in PBMCs incubated with 10-fold and 100-fold above Cmax for ceftriaxone, and
flucloxacillin; however, piperacillin/tazobactam and isoniazid indicated no differences in percentages of
viable lymphocytes across concentrations tested.
CONCLUSION The LDH cytotoxicity and 7-AAD cell viability staining techniques both demonstrate
increased cell death corresponding to a loss in ELISpot sensitivity, with use of higher antimicrobial drug
concentrations for ex vivo diagnostic IFN- ELISpot assays. For all the antimicrobials evaluated, the use of
Cmax and 10-fold Cmax concentrations impacts cell viability and potentially affects ELISpot performance.
These findings inform future approaches for ex vivo diagnostics such as IFN- release ELISpot.
The Role of Immunological and Clinical Biomarkers to
Predict Clinical COVID-19 Severity and Response to
Therapy—A Prospective Longitudinal Study
Ana Copaescu1,2,3*†, Fiona James1†, Effie Mouhtouris1, Sara Vogrin4, Olivia C. Smibert5, Claire L.
Gordon5,6, George Drewett5, Natasha E. Holmes1,5,7‡ and Jason A. Trubiano1,5,8,9‡
1 Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia,
2 Clinical Immunology and Allergy, Department of Medicine, McGill University Health Center, Montreal, QC, Canada,
3 The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada, 4 Department of Medicine, St Vincent’s Hospital, University of Melbourne, Fitzroy, VIC, Australia,
5 Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, VIC, Australia,
6 Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia,
7 Department of Critical Care, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia,
8 Department of Oncology, Sir Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, VIC, Australia, 9 The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
Background: The association of pro-inflammatory markers such as interleukin-6 (IL-6) and other
biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however
their kinetics, response to current COVID-related treatments, association with disease severity and
comparison with other disease states associated with potential cytokine storm (CS) such as
Staphylococcus aureus bacteraemia (SAB) are ill-defined.
Methods: A cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited
– blood sampling was performed at baseline, post-treatment and hospital discharge. Serum IL-6,
C-reactive protein (CRP) and other laboratory investigations were compared between treatment
groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with
suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients
hospitalized for any non-infectious condition (NIC).
Results: IL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared
to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in
SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017); 12.50 pg/mL (3.06,
35.77) in patients with NIC; and 95.51 pg/mL (52.17,
756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge
timepoints. This reduction was amplified in patients treated with remdesivir and/or
dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID- 19 severity.
Conclusions: Knowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease
severity in COVID-19 over common investigations such as CRP and vital signs.
Gordon CL1,2*, Smibert OC1,3*, Holmes NE1,2,Chua KYL 1, Rose M1, Drewett G1, James F1, Mouhtouris E1, Nguyen THO2, Zhang W2, Kedzierski L2,
Rowntree LC2, Chua BY2, Caly L4, Catton MG4, Druce J4, Sait M5, Seemann T5, Sherry NL1,5, Howden BP1,5, Kedzierska K2, Kwong JC1,2^, Trubiano JA1,2,3^ Defective SARS-CoV-2 immune responses in an immunocompromised individual with prolonged viral replication 1. Austin Health 2. University of Melbourne 3. Peter McCallum Cancer Centre 4.Victorian Infectious Diseases Reference Laboratory 5. Microbiological Diagnostic Unit Public Health Laboratory * Authors contributed equally to this study; ^ Authors contributed equally to this study Aim Global research efforts are focused on understanding the optimal immune responses to SARS-CoV-2 to facilitate design of vaccine and treatments. Observation of SARS-CoV-2-specific immune response in individuals with defined immune deficiencies help reveal critical aspects of viral immune control. Methods We describe SARS-CoV-2-specific immune responses in a patient with lymphoma and recent PD-1 inhibitor therapy with late onset of severe COVID- 19 disease and prolonged SARS-CoV-2 replication, in comparison to age- matched and immunocompromised controls. Results Immune profiles showed medium to high levels of HLA-DR+/CD38+-activation in the absence of B cells and PD-1 expression. Antibody responses towards the SARS-CoV-2 receptor binding domain (RBD) were absent, and SARS-CoV- 2 specific T cells were minimally detected. High levels of IL-6 and IL-18 were
detected although levels of several other proinflammatory cytokines (IFN-2,
TNF-, IL-8, IL-12p70, IL-23 and IL-33) were at a lower level compared to healthy controls. The patient’s lack of humoral and cellular immune control of SARS-CoV-2, together with disordered cytokine response, potentially contributed to persistent viral replication and clinical decline 33 days into illness resulting in death. Conclusion Our case illustrates defects in SARS-CoV-2-specific immune responses and persistent viral replication in a patient with lymphoma and recent PD-1 inhibitor therapy. Our analysis of SARS-CoV-2-specific immune parameters may shed new light on which immune pathways are important in controlling SARS-CoV-2 replication and preventing severe disease.
Zhang W1, Chua BY 1,2, Selva K1, Kedzierski L 1, Ashhurst TM3, Boyd DF4, Heycroft E1, Hensen L1, James F5, Mouhtouris E5, Chua K5, Drewett G5, Copaescu A5, Rowntree LC1, Habel JR1, Clemens EB1, Jia X1, Allen L1, Mordant FL1, Amanat F6, Krammer F6, King NJC3, Nicholson S7, Mackay LK1, Thomas PG4, Chung AW1, Kwong JC1,5, Holmes NE1,5, Smibert OC5,8, Nguyen THO1#, Kedzierska K1,2#, Trubiano JA1,5,8#, Gordon CL1,5#
Immune responses in the respiratory tract and blood of COVID-19 patients reveal mechanisms of disease severity
1. University of Melbourne 2. Hokkaido University 3. University of Sydney 4. St Jude Children’s Research Hospital 5. Austin Health 6. Icahn School of Medicine at Mount Sinai 7. The Royal Melbourne Hospital 8. Peter McCallum Cancer Centre #Authors contributed equally to this study.
Aim The respiratory tract is the primary site of SARS-CoV-2 infection yet the mechanisms underlying respiratory tract disease pathogenesis are unknown.
Methods We prospectively collected paired longitudinal blood and respiratory tract samples from patients with confirmed or suspected COVID-19 infection admitted to Austin Health. Cellular, humoral and cytokine responses were analysed and correlated with clinical data.
Results Longitudinal blood samples were obtained from 60 hospitalised patients with confirmed COVID-19, 17 (28%) of which were admitted to intensive care. Paired respiratory samples were collected from 10 COVID-19 patients (endotracheal aspirate [ETA]=10, sputum=3, pleural fluid=1) and 6 hospitalised non-COVID controls (ETA=5, sputum=1). Virus-specific IgG, IgM, and IgA antibodies were detected in the respiratory tract of COVID-19 patients, with RBD IgG and IgM levels being lower in respiratory specimens in comparison to plasma, while RBD IgA levels were elevated. Viral neutralisation was detected when high levels of all RBD isotypes were present. Strikingly, cytokine/chemokine levels and profiles greatly differed to those found in plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils.
Conclusion Respiratory immune responses in COVID-19 are distinct from those found in the blood and may play a role in disease severity and treatment response.
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2021 ResearchFest Infectious Diseases and Medical Imaging