Publications by authors named "Gerard Goh"

46 Publications

Feasibility of the vaccine development for SARS-CoV-2 and other viruses using the shell disorder analysis.

Pac Symp Biocomput 2021 ;26:143-153

Goh's BioComputing, Singapore 548957, Republic of Singapore,

Several related viral shell disorder (disorder of shell proteins of viruses) models were built using a disorder predictor via AI. The parent model detected the presence of high levels of disorder at the outer shell in viruses, for which vaccines are not available. Another model found correlations between inner shell disorder and viral virulence. A third model was able to positively correlate the levels of respiratory transmission of coronaviruses (CoVs). These models are linked together by the fact that they have uncovered two novel immune evading strategies employed by the various viruses. The first involve the use of highly disordered "shape-shifting" outer shell to prevent antibodies from binding tightly to the virus thus leading to vaccine failure. The second usually involves a more disordered inner shell that provides for more efficient binding in the rapid replication of viral particles before any host immune response. This "Trojan horse" immune evasion often backfires on the virus, when the viral load becomes too great at a vital organ, which leads to death of the host. Just as such virulence entails the viral load to exceed at a vital organ, a minimal viral load in the saliva/mucus is necessary for respiratory transmission to be feasible. As for the SARS-CoV-2, no high levels of disorder can be detected at the outer shell membrane (M) protein, but some evidence of correlation between virulence and inner shell (nucleocapsid, N) disorder has been observed. This suggests that not only the development of vaccine for SARS-CoV-2, unlike HIV, HSV and HCV, is feasible but its attenuated vaccine strain can either be found in nature or generated by genetically modifying N.
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March 2021

Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches.

J Hypertens 2021 Mar 3. Epub 2021 Mar 3.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia, Perth, Western Australia Department of Radiology, Alfred Hospital Department of Surgery, Central Clinical School, Monash University, Melbourne, Victoria Medical School, The University of Western Australia, Perth, Western Australia Baker Heart and Diabetes Institute, Melbourne, Victoria Department of Endocrinology, Medical School, The University of Western Australia Department of Radiology, Royal Perth Hospital, Perth, Western Australia Human Neurotransmitter Lab Neurovascular Hypertension & Kidney Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth, Western Australia, Australia.

Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence. A clinical need exists for complementary therapies to curb the burden of cardiometabolic diseases. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. The experience from catheter-based renal denervation studies clearly demonstrates the feasibility, safety and efficacy of such an approach. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multiorgan neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum offering a holistic approach.
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http://dx.doi.org/10.1097/HJH.0000000000002839DOI Listing
March 2021

Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.

Clin Res Cardiol 2021 Feb 26. Epub 2021 Feb 26.

Dobney Hypertension Centre, Faculty of Medicine, School of Medicine-Royal Perth Hospital Unit, Dentistry and Health Sciences, The University of Western Australia, Level 3, MRF Building, Rear 50 Murray St, Perth, WA, 6000, Australia.

Background: Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease.

Objectives: We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up.

Methods: Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety.

Results: All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (- 88%, p = 0.005), kidneys (- 78%, p < 0.001), pancreas (- 78%, p = 0.018) and duodenum (- 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up.

Conclusions: Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.
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http://dx.doi.org/10.1007/s00392-021-01814-1DOI Listing
February 2021

Shell disorder and the HIV vaccine mystery: lessons from the legendary Oswald Avery.

J Biomol Struct Dyn 2021 Jan 7:1-10. Epub 2021 Jan 7.

Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

The search for a human immunodeficiency virus (HIV) vaccine has spanned nearly four decades without much success. A much needed paradigm shift can be found in the abnormally high levels of intrinsic disorder in the outer shells of HIVs, the hepatitis C virus (HCV), and herpes simplex viruses (HSVs), for which successful vaccines have not been established. On the other hand, this feature (high levels of intrinsic disorder in the outer shells) is completely absent in classic viruses for which effective vaccines are found, such as the rabies virus. The motions arising from the disordered outer shell result in the inability of antibodies to bind tightly to the polysaccharides on the viral surface proteins, and, therefore, induce inadequate immune response. Experiments conducted by the legendary Avery Oswald in the 1920s form the theoretical underpinning of this new model. Failures of the vaccines based on the HIV glycoprotein Gp120 and other vaccines can be traced back to the lack of understanding of the important roles of shell disorder in a "Trojan-horse" immune evasion mechanism utilized by the virus. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1870562DOI Listing
January 2021

Marked losses of computed tomography-derived skeletal muscle area and density over the first month of a critical illness are not associated with energy and protein delivery.

Nutrition 2021 02 19;82:111061. Epub 2020 Nov 19.

Nutrition Department, Alfred Health, Melbourne, Australia; Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Australia.

Objectives: Changes in muscularity during different phases of critical illness are not well described. This retrospective study aimed to describe changes in computed tomography (CT)-derived skeletal muscle area (SMA) and density (SMD) across different weeks of critical illness and investigate associations between changes in these parameters and energy and protein delivery.

Methods: Thirty-two adults admitted to the intensive care unit (ICU) who had ≥2 CT scans at the third lumbar area performed ≥7 d apart were included in the study. CT-derived SMA (cm) and SMD (Hounsfield units) were determined using specialized software. A range of clinical and nutrition variables were collected for each day between comparator scans. Associations were assessed by Pearson or Spearman correlations.

Results: There was a significant decrease in SMA between the two comparator scans where the first CT scan was performed in ICU wk 1 (n = 20; P < .001), wk 2 (n = 11; P < .007), and wk 3 to 4 (n = 7; P = .012). There was no significant change in SMA beyond ICU wk 5 to 7 (P = .943). A significant decline in SMD was observed across the first 3 wk of ICU admission (P < .001). Overall, patients received a mean 24 ± 6 kcal energy/kg and 1.1 ± 0.4 g protein/kg per study day and 83% of energy and protein requirements according to dietitian estimates. No association between SMA or SMD changes and nutrition delivery were found.

Conclusions: Critically ill patients experience marked losses of SMA over the first month of critical illness, attenuated after wk 5 to 7. Energy and protein delivery were not associated with degree of muscle loss.
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http://dx.doi.org/10.1016/j.nut.2020.111061DOI Listing
February 2021

SPLEnic salvage and complications after splenic artery EmbolizatioN for blunt abdomINal trauma: the SPLEEN-IN study.

CVIR Endovasc 2020 Dec 7;3(1):92. Epub 2020 Dec 7.

Department of Radiology, Alfred Health, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

Background: As an adjunct to non-operative management, splenic artery embolization (SAE) has been increasingly utilized throughout the world and is now the standard of care for hemodynamically stable patients. This study aimed to retrospectively assess the rate of splenic salvage and complications after SAE for blunt trauma at a level 1 trauma center using the 2018 update to the AAST criteria, and further sub-stratify the role of angiography in AAST grade III injuries with significant hemoperitoneum. All patients between 1 January 2009 and 1 January 2019 who underwent blunt trauma and proceeded to embolization were included. Data was collected concerning initial injury grade, location of embolization, type of embolic material used, complications, and need for subsequent splenectomy. Technical success was defined as successful angiographic occlusion of the target artery at the conclusion of embolization. Clinical success was defined as splenic salvage at discharge. Vascular lesions were characterized including those with active bleeding, pseudoaneurysm, and arterio-venous fistula.

Results: Two hundred thirty-two patients were included in the study. Treatments were performed at a median of 0 days (range 0-28 days) and the median AAST grade was IV (range III-V). Technical success was achieved in all patients. There were 13 complications (5.6%) consisting of re-bleed (9, 3.9%), infarction (3, 1.3%), and access site haematoma (1, 0.43%). Clinical success was achieved in 97% of patients with 7 patients requiring splenectomy after SAE (3.0%) at a median time of 4 days (range 0-17 days). Angiography in patients with grade III injuries identified 18 occult vascular injuries not identified at initial CT (p < 0.0001).

Conclusions: The SPLEEN-IN study shows that treatment of intermediate-high grade blunt force traumatic splenic injuries using SAE resulted in a low rate of complication and splenic salvage in 97% of patients, providing a safe and effective treatment in stable patients. In addition, angiography of grade III injuries identified occult vascular lesions and may warrant treatment of select patients in this cohort.

Level Of Evidence: Level 3.
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http://dx.doi.org/10.1186/s42155-020-00185-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719586PMC
December 2020

Is IR an Essential Hospital Service? Analysis of Trauma Procedures at a Level 1 Centre During the First Wave of COVID-19 Pandemic in Australia.

Cardiovasc Intervent Radiol 2021 02 9;44(2):354-356. Epub 2020 Oct 9.

Department of Radiology, Alfred Health, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

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http://dx.doi.org/10.1007/s00270-020-02664-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546385PMC
February 2021

A Novel Strategy for the Development of Vaccines for SARS-CoV-2 (COVID-19) and Other Viruses Using AI and Viral Shell Disorder.

J Proteome Res 2020 11 2;19(11):4355-4363. Epub 2020 Oct 2.

Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida 33620, United States.

A model that predicts levels of coronavirus (CoV) respiratory and fecal-oral transmission potentials based on the shell disorder has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Using primarily the PID of N, SARS-CoV-2 is grouped as having intermediate levels of both respiratory and fecal-oral transmission potentials. Related studies, using similar methodologies, have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and case-fatality rates of 0.5-5% and 10.9%, respectively. The underlying relationship between virulence and respiratory potentials has to do with the viral loads of vital organs and body fluids, respectively. Viruses can spread by respiratory means only if the viral loads in saliva and mucus exceed certain minima. Similarly, a patient is likelier to die when the viral load overwhelms vital organs. Greater disorder in inner shell proteins has been known to play important roles in the rapid replication of viruses by enhancing the efficiency pertaining to protein-protein/DNA/RNA/lipid bindings. This paper suggests a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells (N) of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore, this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its greater contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.
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http://dx.doi.org/10.1021/acs.jproteome.0c00672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640981PMC
November 2020

Implanon NXT embolisation into the pulmonary arterial tree.

Aust J Gen Pract 2020 09;49(9):585-586

BBiomedSc (Hons), MBBS, FRANZCR, EBIR, Consultant Interventional Radiologist, Department of Radiology, Alfred Hospital, Vic; Department of Surgery, Monash University, Vic.

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http://dx.doi.org/10.31128/AJGP-12-19-5175DOI Listing
September 2020

Shell Disorder Analysis Suggests That Pangolins Offered a Window for a Silent Spread of an Attenuated SARS-CoV-2 Precursor among Humans.

J Proteome Res 2020 11 27;19(11):4543-4552. Epub 2020 Aug 27.

Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida 33620, United States.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (Nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. With M = 8.6% and N = 50.2%, the 2003 SARS-CoV falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M = 9%, N = 44%) and SARS-CoV-2 (M = 5.5%, N = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M = 5.5% has one of the hardest outer shells among CoVs. Because the hard shell is able to resist the antimicrobial enzymes in body fluids, the infected person is able to shed large quantities of viral particles via saliva and mucus, which could account for the higher contagiousness of SARS-COV-2. Further searches have found that high rigidity of the outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M = 5.6%) and pangolins (M = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017 to 2019 reveals that pangolins provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in both the genetic proximity of the pangolin-CoVs to SARS-CoV-2 (∼90%) and differences in N disorder. A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N (44.8%). Our shell disorder model predicts this to be a SARS-CoV-2 vaccine strain, as lower inner shell disorder is associated with the lesser virulence in a variety of viruses.
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http://dx.doi.org/10.1021/acs.jproteome.0c00460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640969PMC
November 2020

Comparison of Ultrasound-Derived Muscle Thickness With Computed Tomography Muscle Cross-Sectional Area on Admission to the Intensive Care Unit: A Pilot Cross-Sectional Study.

JPEN J Parenter Enteral Nutr 2021 01 15;45(1):136-145. Epub 2020 Apr 15.

Nutrition Department, Alfred Health, Melbourne, Australia.

Introduction: The development of bedside methods to assess muscularity is an essential critical care nutrition research priority. We aimed to compare ultrasound-derived muscle thickness at 5 landmarks with computed tomography (CT) muscle area at intensive care unit (ICU) admission. Secondary aims were to (1) combine muscle thicknesses and baseline covariates to evaluate correlation with CT muscle area and (2) assess the ability of the best-performing ultrasound model to identify patients with low CT muscle area.

Methods: Adult patients who underwent CT scanning at the third lumbar area <72 hours after ICU admission were prospectively recruited. Muscle thickness was measured at mid-upper arm, forearm, abdomen, and thighs. Low CT muscle area was determined using published cutoffs. Pearson correlation compared ultrasound-derived muscle thickness and CT muscle area. Linear regression was used to develop ultrasound prediction models. Bland-Altman analyses compared ultrasound-predicted and CT-measured muscle area.

Results: Fifty ICU patients were enrolled, aged 52 ± 20 years. Ultrasound-derived muscle thickness at each landmark correlated with CT muscle area (P < .001). The sum of muscle thickness at mid-upper arm and bilateral thighs, including age, sex, and the Charlson Comorbidity Index, improved the correlation with CT muscle area (r = 0.85; P < .001). Mean difference between ultrasound-predicted and CT-measured muscle area was -2 cm (95% limits of agreement, -40 cm to +36 cm ). The best-performing ultrasound model demonstrated good ability to identify 14 patients with low CT muscle area (area under curve = 0.79).

Conclusion: Ultrasound shows potential for assessing muscularity at ICU admission (Clinicaltrials.gov NCT03019913).
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http://dx.doi.org/10.1002/jpen.1822DOI Listing
January 2021

Shell disorder analysis predicts greater resilience of the SARS-CoV-2 (COVID-19) outside the body and in body fluids.

Microb Pathog 2020 Jul 31;144:104177. Epub 2020 Mar 31.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow region, Russia.

The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread.
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http://dx.doi.org/10.1016/j.micpath.2020.104177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118597PMC
July 2020

Accuracy of dual-bolus CT in the diagnosis of active arterial bleeding in adult pelvic trauma.

J Med Imaging Radiat Oncol 2020 Jun 3;64(3):326-330. Epub 2020 Apr 3.

Department of Radiology, Alfred Hospital, Melbourne, Victoria, Australia.

Introduction: A single-phase dual-bolus CT (DB-CT) simultaneously opacifies both arterial and venous systems and can be utilised in the trauma setting to aid in the diagnosis of active bleeding while also allowing for optimal assessment of the abdominal and pelvic viscera. Active bleeding can be venous or arterial, the latter being amenable to angiography and potentially embolisation. We aimed to establish the accuracy of single-phase DB-CT vs commonly performed portal venous CT (PV-CT) in the diagnosis of active bleeding when compared to formal digital subtraction angiography as the gold standard.

Methods: All patients diagnosed with active bleeding on PV-CT or DB-CT at a level 1 tertiary centre over a 6-year period and who subsequently proceeded to digital subtraction angiography (DSA) were included for analysis. The initial CT images were retrospectively reviewed by two consultant interventional radiologists who were blinded to the subsequent outcome of the DSA and to each other's results. The sensitivity, specificity and inter-observer agreement between the two readers was then able to be assessed.

Results: A total of 60 patients were included in the analysis. Sensitivity for the diagnosis for any active bleeding was high for both DB-CT and PV-CT (range 88.9%-100%) while diagnosis of specifically arterial bleeding was comparatively lower (51.9%-79%). Inter-observer agreement for the identification of arterial bleeding was better for DB-CT (fair) compared to PV-CT (poor).

Conclusion: Both PV-CT and DB-CT demonstrate high sensitivity in the diagnosis of any active bleeding though identification of specifically arterial bleeding is lower for both scanning methods. Nevertheless, inter-observer reliability for the identification of arterial bleeding is higher for DB-CT. Multi-phase arterial and venous CT may yield better results and could be a focus for future studies.
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http://dx.doi.org/10.1111/1754-9485.13030DOI Listing
June 2020

Omental apoplexy: Unravelling the mystery.

J Med Imaging Radiat Oncol 2020 Jun 25;64(3):319-325. Epub 2020 Mar 25.

Department of Radiology, Alfred Hospital, Melbourne, Victoria, Australia.

Introduction: To describe cases omental haemorrhage and to review the literature on this topic.

Methods: We describe three cases of spontaneous omental haemorrhage and discuss various management strategies, in an attempt to provide direction for similar cases in the future.

Results: A number of case reports of spontaneous or idiopathic omental haemorrhage exist in the literature. These cases are often attributed to an underlying vasculopathy, such as segmental arterial mediolysis (SAM). Appropriate resuscitation is paramount for best outcome. Severe bleeding may require surgery or transcatheter arterial embolisation, which is best performed early if required. Endovascular management using selective catheterisation of the bleeding vessel and embolisation is a minimally invasive alternative to emergent operative intervention. In the three cases we present, endovascular embolisation was performed in two patients, and surgical ligation in a third. Segmental arterial mediolysis is considered the likely aetiology in at least 2 of the 3 cases, based on imaging findings. No further episodes of haemorrhage occurred at follow-up (ranging from 6 months to 2 years).

Conclusions: Acute omental haemorrhage is a rare condition; however, it may be associated with significant morbidity and mortality. CT angiography is the imaging of choice. Management strategies include both endovascular and surgical intervention.
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http://dx.doi.org/10.1111/1754-9485.13024DOI Listing
June 2020

What is a modern Interventional Radiologist in Australia and New Zealand?

J Med Imaging Radiat Oncol 2020 Jun 20;64(3):361-365. Epub 2020 Mar 20.

Department of Radiology, Alfred Health, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/1754-9485.13014DOI Listing
June 2020

Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity.

Biomolecules 2020 02 19;10(2). Epub 2020 Feb 19.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.

The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002-2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.
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http://dx.doi.org/10.3390/biom10020331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072294PMC
February 2020

Treatment of symptomatic fibroid disease using uterine fibroid embolisation: An Australian perspective.

Aust N Z J Obstet Gynaecol 2020 06 20;60(3):324-329. Epub 2020 Jan 20.

Department of Radiology, Alfred Health, Melbourne, Victoria, Australia.

Uterine leiomyomata (fibroids) are symptomatic in up to 35% of women and treatment can be a costly burden to the individual and society. Options for treatment range from non-hormonal, hormonal, minimally invasive, to surgery. While symptoms from smaller fibroids may respond to simple treatment, those with larger fibroids or with a large volume of disease require a more definitive option. Surgery (hysterectomy or myomectomy) are both well-established treatment modalities with good clinical outcomes. Since the 1990s, uterine fibroid embolisation has emerged as a less invasive option for women than for surgical techniques, while level 1 evidence shows that in the short to mid-term, there is a similar improvement in symptom-related quality of life outcomes to surgery, but with reduced hospital stay and reduced cost. However, in the longer term there may be a need for further treatment or retreatment in some patients compared with surgery. Since its introduction, uptake of this procedure in Australia has been low relative to surgical options. This manuscript reviews the current literature surrounding treatment, along with the trends in uptake of embolisation by Australian women, places this in context of current guidelines from major societies, and encourages gynaecologists and interventional radiologists to be aware of the advantages and limitations of embolisation.
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http://dx.doi.org/10.1111/ajo.13120DOI Listing
June 2020

Nipah shell disorder, modes of infection, and virulence.

Microb Pathog 2020 Apr 12;141:103976. Epub 2020 Jan 12.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow region, Russia. Electronic address:

The Nipah Virus (NiV) was first isolated during a 1998-9 outbreak in Malaysia. The outbreak initially infected farm pigs and then moved to humans from pigs with a case-fatality rate (CFR) of about 40%. After 2001, regular outbreaks occurred with higher CFRs (~71%, 2001-5, ~93%, 2008-12). The spread arose from drinking virus-laden palm date sap and human-to-human transmission. Intrinsic disorder analysis revealed strong correlation between the percentage of disorder in the N protein and CFR (Regression: r = 0.93, p < 0.01, ANOVA: p < 0.01). Distinct disorder and, therefore, genetic differences can be found in all three group of strains. The fact that the transmission modes of the Malaysia strain are different from those of the Bangladesh strains suggests that the correlations may also be linked to the modes of viral transmission. Analysis of the NiV and related viruses suggests links between modes of transmission and disorder of not just the N protein but, also, of M shell protein. The links among shell disorder, transmission modes, and virulence suggest mechanisms by which viruses are attenuated as they passed through different cell hosts from different animal species. These have implications for development of vaccines and epidemiological molecular analytical tools to contain outbreaks.
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http://dx.doi.org/10.1016/j.micpath.2020.103976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126952PMC
April 2020

The cost to perform uterine fibroid embolisation in the Australian public hospital system.

J Med Imaging Radiat Oncol 2020 Feb 2;64(1):18-22. Epub 2019 Dec 2.

Department of Radiology, Alfred Health, Melbourne, Victoria, Australia.

Introduction: Uterine fibroids have the potential to cause morbidity, and there is a substantial cost to both the healthcare system and society. There is support for minimally invasive intervention, and uterine fibroid embolisation (UFE) is an established cost-effective option for women wishing for an alternative to surgery. There is a lack of local Australian costing data to compliment use in the public hospital system, and we offer a costing analysis of running a public hospital service.

Methods: We reviewed the costs for 10 sequential uterine fibroid embolisation cases, by assessing the direct and indirect hospital costs.

Results: The total cost of providing a uterine fibroid embolisation service using our model in a public hospital including initial outpatient assessment, procedure costs, overnight hospital ward stay and outpatient follow-up is $3995 per admission.

Conclusion: Using our model, the overall cost to perform this procedure is low, and lower than prior estimates for surgical alternatives. We encourage government and regulatory bodies to support UFE through guidelines and remuneration models, and encourage more public Australian interventional radiology departments to offer this service.
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http://dx.doi.org/10.1111/1754-9485.12982DOI Listing
February 2020

Stratification of Pre-procedure Risk Factors Associated with Difficult-to-remove Inferior Vena Cava (IVC) Filters: A 6-year Retrospective Analysis at a Tertiary Center.

Cardiovasc Intervent Radiol 2020 Feb 12;43(2):238-245. Epub 2019 Nov 12.

Department of Radiology, Alfred Health, Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

Purpose: Currently, data surrounding predicting difficulty of IVC filter retrievals are heterogenous and conflicting. We aimed to identify which of many variables associated with IVC filters is a risk for procedural difficulty.

Materials And Methods: This study retrospectively reviewed 6 years of IVC filter retrievals at a tertiary center identifying 356 consecutive retrievals. A difficult retrieval was defined as any case where the fluoroscopy time exceeded 7 min, an advanced technique was required, the retrieval attempt failed and required an additional attempt or was left permanent, or there was major complication such as IVC filter fracture/migration/vessel injury.

Results: There were 105 filter retrievals defined as difficult (29.5%). Univariate analysis showed significantly increased risk for retrievals with an embedded top. Multivariate analysis assessed the association between dwell time, tilt, age, non-hooked filters, leg penetration and difficult retrieval. This showed a significant increase in the difficulty of retrieval for filters tilted between 5° and 15° (odds ratio 2.38, p < 0.001), for filters tilted more than 15° (odds ratio 7.91, p < 0.001), and dwell time greater than 6 months (odds ratio 2.06, p = 0.033). No significant increase in difficulty was seen with filters with a dwell time of less than 6 months, leg penetration, non-hooked filters, or with increasing patient age.

Conclusions: Identifying these risks in patients in advance of the procedure allows appropriate planning and improved workflow efficiency.
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http://dx.doi.org/10.1007/s00270-019-02373-9DOI Listing
February 2020

Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity.

Biomolecules 2019 11 6;9(11). Epub 2019 Nov 6.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.

(ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015-2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV ( = 0.9) and DENV-2 (DENV-2 + ZIKV, = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses ( = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.
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http://dx.doi.org/10.3390/biom9110710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920988PMC
November 2019

After-hours emergency radiology CT reporting by radiology registrars at an Australian level 1 trauma centre: A review of discrepancies between preliminary and final reports.

J Med Imaging Radiat Oncol 2019 Oct 28;63(5):567-572. Epub 2019 Jun 28.

Radiology Department, Alfred Hospital, Melbourne, Victoria, Australia.

Introduction: There is reliance on radiology registrar reporting of after-hours CT scans in many public hospitals across Australia and New Zealand. This study evaluates the extent and nature of CT reporting discrepancies after-hours by comparing trainee preliminary reports with consultant finalised reports.

Methods: A retrospective review of all after-hours CT scans between January and December 2014 by radiology trainees at a level 1 trauma centre was performed. Discrepancies were classified as major or minor, by year level of trainee, time of report and scan type (Trauma vs. Non-Trauma). Major discrepancies were investigated to assess if they led to increased morbidity, mortality or a change in treatment.

Results: 17,948 after-hours CT scans were performed. A total of 1235 preliminary reports required addendums (discrepancy rate of 6.9%). There were 630 Trauma and 605 Non-Trauma studies. There were 56 major (0.3%) and 1179 minor (6.6%) discrepancies. Of the 56 major discrepancies there were 12 (0.3%) in the Trauma and 44 (6.6%) in the Non-Trauma groups. There were no adverse patient outcomes due to any major discrepancy. There were more minor discrepancies in reports of Trauma CTs compared to Non-Trauma (P ≤ 0.0001). No relationship between the time of report issued and discrepancy rate (P = 0.811) was observed. There was a lower discrepancy rate the more experienced the registrar from year 2 to advanced fellowship (P = 0.003).

Conclusion: The discrepancy rates of after-hours CT trainee reports were lower at this institution compared to international literature (6.9% vs. 7.7%). The majority of preliminary trainee reports were accurate with no increased morbidity or mortality resulting from major discrepancies.
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http://dx.doi.org/10.1111/1754-9485.12921DOI Listing
October 2019

The interaction between irreversible electroporation therapy (IRE) and embolization material using a validated vegetal model: an experimental study.

Diagn Interv Radiol 2019 Jul;25(4):304-309

Department of Radiology, The Alfred Hospital, Victoria, Australia; Department of Surgery, Monash University, Melbourne, Australia.

Purpose: Irreversible electroporation (IRE) is a nonthermal tumor ablation technique that induces cell apoptosis while preserving extracellular architecture. Surgical clips and embolic agents may lie adjacent to, or within, the target lesion. It is unknown to date if IRE causes degradation to the embolic agents or surgical clips that may have adverse effects to patients. We aimed to examine the effects of the IRE on the morphology of various embolic agents and the effects of these agents to the ablation field using a previously validated vegetal model.

Methods: Metallic surgical clips and various metallic and nonmetallic embolic agents were inserted within the center of the tuber ablation field. Additionally, clips were inserted on the edge and outside the ablation field. One tuber was ablated as a control. Ablation settings were based on previous published experiments. Tubers were imaged with magnetic resonance imaging (MRI) 18-24 hours after ablation and the ablated field dimensions were measured. Nonmetallic embolic agents were examined microscopically by the pathologist.

Results: Nonmetallic agents did not affect the ablation pattern. Metallic implants, however, caused arcing of the ablation margins. There was no macroscopic or microscopic degradation to the agents after IRE.

Conclusion: The ablation zone arced in the presence of surgical clips at the edge or outside the ablation margins; therefore, nearby critical structures may be susceptible to the effects of IRE. Furthermore, there was no physical degradation of the embolic agents or surgical clips, and this may have importance when considering IRE ablation of previously embolized lesions in vivo.
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http://dx.doi.org/10.5152/dir.2019.18361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622437PMC
July 2019

The Safety of Continuing Therapeutic Anticoagulation During Inferior Vena Cava Filter Retrieval: A 6-Year Retrospective Review from a Tertiary Centre.

Cardiovasc Intervent Radiol 2019 Aug 28;42(8):1110-1116. Epub 2019 May 28.

Department of Radiology, Alfred Health, Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

Purpose: Assess the safety of inferior vena cava (IVC) filter retrieval in patients taking anticoagulation, compared to a non-anticoagulated cohort.

Materials And Methods: Single-centre retrospective analysis of patients who underwent IVC filter retrieval between January 2012 and February 2018. Information about patient demographics, anticoagulation, tilt, major and minor complications was collected. Major complications were defined as: IVC injury from the filter retrieval, retained fragment of filter, filter fracture and filter embolisation. Minor complications were defined as: neck haematoma and puncture site infection.

Results: Total of 357 patients (age 18-95, Male: 231) underwent IVC filter retrieval, comprising of Cook Celect Platinum, Cook Celect, and ALN-branded filters. Of these 182 patients were on anticoagulation and 175 patients were not on anticoagulation, based on the indication for the filter (thrombosis or prophylaxis) and at the discretion of the referring unit who were managing the anticoagulation. IVC filter retrieval was technically successful in 349 patients. Five major complications (1.4% of retrievals) were recorded and no minor complications (0% of retrievals). In the anticoagulation cohort, there were two major complications (1.1% of retrievals) both related to IVC injury. In the non-anticoagulated cohort, there were three major complications (1.7% of retrievals) relating to filter embolisation, IVC injury, and filter fracture.

Conclusions: IVC filter retrieval is a safe procedure with a low complication rate. Being on anticoagulation does not increase the risk of a major complication or change the management of major complication compared with a non-anticoagulated cohort. IVC filter retrieval is safe to perform in patients currently taking prophylactic or therapeutic anticoagulation based on our cohort.

Level Of Evidence: Level 3, retrospective cohort study.
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http://dx.doi.org/10.1007/s00270-019-02254-1DOI Listing
August 2019

HIV Vaccine Mystery and Viral Shell Disorder.

Biomolecules 2019 05 8;9(5). Epub 2019 May 8.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.

Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.
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http://dx.doi.org/10.3390/biom9050178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572542PMC
May 2019

Randomized and controlled study comparing patient controlled and radiologist controlled intra-procedural conscious sedation, using midazolam and fentanyl, for patients undergoing insertion of a central venous line.

J Med Imaging Radiat Oncol 2018 Dec 8;62(6):781-788. Epub 2018 Oct 8.

Queensland Diagnostic Imaging, Holy Spirit Northside Hospital, Brisbane, Queensland, Australia.

Introduction: Interventional Radiology procedures can provoke anxiety and may be painful. Current practice, Radiologist Controlled Sedation (RCS), involves titrating aliquots of midazolam and fentanyl to patient response but underdosing and overdosing may occur. This study tests a new method of titrating sedation/analgesia during the procedure, Patient Controlled Sedation (PCS), in which a combination of fentanyl and midazolam are administered using a patient-controlled analgesia pump. This allows the patient to self-control their sedation/analgesia during the procedure.

Methods: We performed a randomised control trial comparing the effects of pain, sedation, amnesia and overall patient satisfaction between PCS and RCS, by enrolling forty patients undergoing insertion of a tunnelled central line.

Results: Our results showed that PCS was safe, with no adverse events. PCS was effective in providing sedation, amnesia and overall pain relief comparable to RCS. There was no significant difference in dose given to patients using PCS or RCS. There was a tendency for patients in the PCS group to begin sedation later than those in the RCS group, but both were equally sedated during the procedure. We show that patients in the PCS group were very satisfied with the procedure.

Conclusions: We show that PCS is non-inferior to RCS in terms of dosage given and degree of sedation. To the authors' knowledge, this is the first study to show intra-procedural PCS in an Interventional Radiology setting using midazolam and fentanyl as a randomised comparative trial. It has wide applicability in a procedural setting for very low cost and with minimal additional training required.
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http://dx.doi.org/10.1111/1754-9485.12817DOI Listing
December 2018

Establishing a Platform for Interest and Education in Interventional Radiology Amongst Radiology Trainees.

Cardiovasc Intervent Radiol 2019 Jan 20;42(1):95-100. Epub 2018 Sep 20.

Department of Radiology, Alfred Health, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

Purpose: Over recent times, procedural Radiologists have begun to establish themselves as the distinct subspecialty of Interventional Radiology (IR). The Interventional Radiology Society of Australasia (IRSA) was established in 1982 to share collaborative ideas, encourage research, and promote education. IRSA developed a weekend registrar workshop attended by Radiology Registrars from Australia and New Zealand. In the 2018 event, we surveyed the Registrars to identify their interest in IR training before and after the workshop.

Materials And Methods: The event was held over a weekend and consisted of both lectures and hands-on workshops. A survey was handed to all 67 registrants of the workshop and there was a 55% response rate including 78% of females in attendance.

Results: Before the workshop, trainees rated their interest in IR training at a mean of 3.7 out of 5. After the workshop, trainees rated their interest in IR training as an average of 4.4 out of 5 (p < 0.001). The difference in interest between males and females before the workshop (4.0 vs. 3.1) was significant (p = 0.003), however after the workshop (4.5 vs. 4.1) was not significant (p = 0.07). The change in interest from attending the workshop was significant between genders, p = 0.03 (male interest increased mean 0.5, female increased mean 1.0).

Conclusion: We show that a program of lectures and workshops designed to generate interest in IR leads to a significant increase in training interest, particularly amongst females. Other subspecialty groups should consider this type of intervention and promote ongoing education and inspiration.

Level Of Evidence: Cross-sectional study, Level IV.
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http://dx.doi.org/10.1007/s00270-018-2080-3DOI Listing
January 2019

Prolonged balloon tamponade in the initial management of inferior vena cava injury following complicated filter retrieval, without the need for surgery.

J Med Imaging Radiat Oncol 2018 Dec 5;62(6):810-813. Epub 2018 Jul 5.

Department of Radiology, Alfred Health, Melbourne, Victoria, Australia.

Advanced techniques have been described to remove embedded inferior vena cava (IVC) filters including the loop snare and modified loop snare (Hangman) techniques. Retrieval of embedded filters have been associated with higher rates of complications including IVC injury and stenosis. We report two challenging embedded retrievals complicated by IVC injury and haemorrhage. Haemostasis was successfully achieved with prolonged balloon tamponade, suggesting that injury to the IVC during filter retrieval may not need urgent surgery. However, both patients received short-term complications related to caval thrombosis and patients in this cohort should be closely observed after retrieval. These cases support rigorous attention to filter indication and follow-up.
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http://dx.doi.org/10.1111/1754-9485.12758DOI Listing
December 2018