Australian Centre Research Articles

A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies.

PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.

Maternal perception of decreased fetal movements is independent of infant size.

Fetal movements are often used as a surrogate for fetal wellbeing. Previous research suggests a link between maternal perception of decreased fetal movements (DFM) and small for gestational age (SGA) infants. The aim of this study was to investigate the association between maternal presentation with DFM and birthweight centile categories at a large Australian perinatal center. This was a 5-year cohort study (January 2016 to October 2020) of non-anomalous singleton infants born at the Mater Mothers' Hospital in Brisbane, Australia at 28+0 weeks gestation or later. The primary outcome for this study was the rate of DFM by birthweight centile categories. Maternal demographics included age, body mass index, ethnicity, parity, medical conditions, and previous stillbirths. The effect of decreased fetal movements on birthweight centile was evaluated with adjusted multinomial regression models. Adjusted logistic regression models were then used to evaluate whether decreased fetal movements resulted in birthweight centiles <5 and <10. Robust standard errors were used to account for clustering at the patient level. Wald tests, Hosmer and Lemeshow's goodness of fit tests, Akaike's and Bayesian Information Criteria were used to evaluate models. Over the 5-year study period, 45042 women met the inclusion criteria. Of these, 6690 (14.9%) women presented with DFM. Of the DFM cohort, 80.9% (5411/6690) had only one presentation with DFM, whilst 19.1% (1279/6690) had >2 presentations. The overall stillbirth rate was similar in women with DFM (0.1%, 8/6690) and without DFM (0.1%, 50/38352). There was no difference in rates of DFM (either single or multiple) vs. no DFM and infant birthweight centile categories. There was no association between DFM (either single or multiple) and infant birth weight centile. The results of this study suggest that presentation with DFM is not associated with infant size. Clinicians should consider additional risk factors and the overall clinical context in deciding appropriate management. DFM is not necessarily an indication for an immediate or urgent ultrasound scan to assess fetal size. This article is protected by copyright. All rights reserved.

Vitamin D and Lipid Profiles in Infertile PCOS and Non-PCOS Females.

This research is aimed to explore the relationship between vitamin D and lipid profile in females with PCOS and non-PCOS infertile female subjects. Comparative descriptive study. Place and Duration of the Study: Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan and Jinnah Postgraduate Medical Centre, Karachi, Pakistan in collaboration with the Australian Concept Infertility Medical Centre, from February 2021 to March 2023. A total of 180 infertile women with 120 PCOS and 60 non-PCOS were enrolled. The lipid profile and BMI of the patients were acquired from desk records, and vitamin D was estimated by enzyme-linked immunosorbent assay (ELISA). Participants were classified according to their vitamin D levels as sufficient (30-100 ng/ml), insufficient (20-29 ng/ml), or deficient (below 20 ng/ml). Median, interquartile range, frequency, and percentages were described. Statistical significance was calculated by Mann-Whitney U and Chi-square tests with p-values of 0.05. Females with PCOS had significantly low vitamin D (p <0.001). Total cholesterol, low-density lipoprotein, very low-density lipoprotein, and triglyceride levels were significantly increased, and high-density lipoprotein cholesterol (HDL) was less in comparison to the non-PCOS group (p <0.001). A significant increase in total cholesterol, triglycerides, low-density lipoproteins, and very low-density lipoproteins was found in the vitamin D deficient subgroup compared with insufficient or sufficient groups (p = 0.05). The study provides a link between females with PCOS and abnormalities in lipid profile. Decreased vitamin D levels in females with PCOS were linked with an abnormal lipid profile characterised by rise in cholesterol, triglycerides, and low-density lipoproteins which may lead to metabolic abnormalities. Vitamin D, Polycystic ovary syndrome, Metabolic syndrome, Body mass index, Lipid profile.

Sleep Disturbance in Children with Fetal Alcohol Spectrum Disorder and the Relationship to the Neurodevelopmental Profile.

Sleep disturbance is an important feature of fetal alcohol spectrum disorder (FASD). We sought to describe sleep patterns in school-aged children with FASD, in comparison with a typically developing community group, and investigate the relationship between sleep and neurodevelopmental profiles. The FASD cohort (N = 36) was recruited from a tertiary Australian FASD diagnostic center, and the typically developing group (N = 36) was previously recruited as a control cohort for a separate study. Sleep disturbance was assessed with the caregiver-completed Sleep Disturbance Scale for Children (SDSC) questionnaire. Neurodevelopmental assessment results for the 10 domains impaired in FASD were used for correlations with sleep disturbance. In the FASD group, 80% of children scored above the SDSC cutoff, compared with 22% of the control group ( p < 0.001). Statistically significant group differences were seen for all 6 subscales of the SDSC ( p < 0.05). The most frequently affected domains in the FASD group related to difficulties with initiating and maintaining sleep (58%), sleep-wake transition disorders (44%), and disorders of arousal (42%). A statistically significant relationship was not found between sleep and the severity of neurodevelopmental impairment or impairment of a particular domain, acknowledging the limitations of our small sample size. Half of the FASD sample (52%) were taking a pharmaceutical agent to support sleep, which was not associated with lower SDSC scores. In this small study, sleep disturbances were frequently reported by carers of children with FASD, independent of the severity of their neurodevelopmental impairments. Persistent sleep disturbance despite the use of sleep medications highlights the need for prospective studies exploring sleep interventions in this population. Integration of behavioral sleep medicine into management is recommended for all children with FASD.

The Regenerative Vanua Journey: Rekindling the Connection and Regeneration of Vanua through Regenerative Agritourism Experiences

Summary This case study explores the journey of the not-for-profit Regenerative Vanua, which is an organisation operating in the South Pacific and is responsible for research, training and development support for regenerative agritourism and regenerative landscapes. Since its inception, Regenerative Vanua has developed the Regenerative Agritourism Pathway Recognition Program and the Regenerative Agritourism Framework, and in 2022 was awarded the Islands Innovations Award for the programs piloted in Vanuatu. Regenerative Vanua is now collaborating with the Global Agritourism Network, the Pasifika Agritourism Network, the Pacific Islands Forum Secretariat, the World Indigenous Tourism Alliance, Pacific Island Food Revolution, the European Union, the Australian Centre for International Agriculture Research, and the Australian Centre for Pacific Islands Research to apply what has been learned in Vanuatu throughout the Pacific Islands. The first Global Regenerative Agritourism Symposium – held in Vanuatu in June 2024 – spotlights the incredible work being done in the Pacific and allows the world to see that it is Pacific Islanders who are helping to lead us all into a regenerative future. Information © The Authors 2024

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience

Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

DIPG-76. PEDIATRIC PATIENTS WITH DIFFUSE MIDLINE GLIOMA DEMONSTRATE AN UNEXPECTED PREVALENCE OF GERMLINE VARIANTS IN HOMOLOGOUS RECOMBINATION GENES

Abstract BACKGROUND Pediatric patients with Diffuse Midline Gliomas (DMG), H3K27M altered have a dismal prognosis and novel therapeutic approaches are urgently needed. Factors that drive development of pediatric DMG are unknown. METHODS To determine the prevalence of germline pathogenic/likely pathogenic variants (P/LPV) in DMG, we assembled an international cohort of 252 patients with germline whole genome or whole exome sequencing data, including diffuse intrinsic pontine glioma (DIPG; n=153), from Australian, European and North American centres. RESULTS We identified germline P/LPV in cancer predisposition genes in 7.5% (19/252) of patients, mainly homologous recombination (n=9; BRCA1, BRCA2, PALB2) and Fanconi anemia genes (n=4). Germline P/LPV in mismatch repair genes (MSH2, PMS2) were found in two patients. Two patients each had two separate germline P/LPV. The prevalence of germline P/LPV was not significantly different according to age, location of DMG nor H3K27M mutational status. Furthermore, tumor profiles differed, with absence of somatic drivers in the PI3K/mTOR pathway in patients with germline P/LPV compared to those without (P = 0.023). Knockdown of BRCA1 in DMG cell cultures sensitized tumor cells to PARP inhibition. Reflecting the potential therapeutic relevance of these findings, we describe one H3.3 K27M-mutant DMG patient with a pathogenic germline BRCA2 and FANCE variant and multiple recurrences, who was treated with a PARP inhibitor (olaparib) and immune checkpoint inhibitor, leading to a near complete radiological response after 4 months. CONCLUSION Our study is the largest series to date investigating germline P/LPV in cancer predisposition genes in DMG and provides new therapeutic insights. It is expected that these germline findings will also guide cascade testing for a proband’s relatives. Our data highlight the importance of germline testing in H3K27-altered DMG patients at diagnosis.

Gastric intestinal metaplasia: Prevalence in a large Australian center and nationwide survey of endoscopic practice.

Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions. We conducted a single-center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web-based, 25-question, investigator-designed, multiple-choice survey was distributed among all registered endoscopists in Australia. The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low-grade dysplasia, 0.9% had high-grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty-seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high-risk patients. Only 1.5% (n = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG. This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping.

A phase 2 safety and efficacy study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma.

9510 Background: Darovasertib is a protein kinase C (PKC) inhibitor with meaningful activity in metastatic uveal melanoma (UM) due to its effect on PKC delta downstream of canonical GNAQ/GNA11 mutations. To date, its clinical activity in patients with localized primary disease has not been assessed in either neoadjuvant or adjuvant settings. Methods: Patients planned for enucleation with localized UM were treated in an initial safety cohort with darovasertib 300mg BID for 1 month (n=3 patients), and then following DSMB agreement in an expansion cohort for up to 6 months (n=12 patients) as neoadjuvant treatment prior to definitive management (enucleation, plaque brachytherapy or EBRT) across 3 Australian centers. All patients were eligible to receive up to 6 months of adjuvant treatment with darovasertib at investigator discretion after definitive management of their primary tumour. Tumour volume was calculated by the rotational ellipsoid method. Results: 15 patients (male n=7, female n=8; median age 62 years (range, 33-76 years)) were enrolled. At baseline, AJCC tumor stages were T3a (n=5), T3b (n=4), T4a (n=4), T4b (n=2), and the median tumor size (maximum thickness/diameter/volume) was 9.7mm/ 15.6 mm/ 2463 mm3. At datalock; 11/15 patients had completed primary treatment, 4/15 remained on neoadjuvant treatment, 6 patients received adjuvant darovasertib after primary treatment of their UM with 3 patients completing the planned 6-months . Median tumor shrinkage (maximum height/base/volume change) was 11.2%/ 7.6%/ 22.7% after 1 month of treatment and 31.7%/ 11.9% /45.3% after 6 months. At datalock, 6/9 (66%) currently completed neoadjuvant patients were converted to plaque brachytherapy (n=5) or EBRT (n=1) with 3 ongoing. One patient with high-risk cytogenetic features had relapsed with metastatic disease despite receiving 6-months of neoadjuvant darovasertib and another 6-months of adjuvant treatment. Treatment emergent adverse events included postural hypotension (Gr1/2 – 13/13%), syncope (Gr3 – 13%), rash (Gr1/2 – 33/5%), pruritis (Grr1 – 13%), dizziness (Gr1 – 27%), fatigue (Gr1/2 – 30/5%), nausea (Gr1/2 – 73/6%), vomiting (Gr1 – 40%), and diarrhea (Gr1 – 60%). Updated results, histopathological and genomic outcomes will be presented. Conclusions: NADOM provides the first evidence that a globe-salvage neoadjuvant treatment strategy in UM is feasible, safe, and efficacious. The results suggest that PKC inhibition with darovasertib can induce clinically meaningful tumor shrinkage in patients with primary UM patients who otherwise require enucleation. Larger trials are in now progress (NCT05907954) to further quantify visual and oncological outcomes. Clinical trial information: 05187884.

Mutated KRASas a promising target in pancreas cancer: PURPLE registry data to inform real-world incidence and prognostic significance and to aid trial recruitment.

11150 Background: With around 90% KRASmutation (mt) frequency, pancreatic ductal adenocarcinoma (PDAC) is considered the most RAS-addicted cancer. Despite guideline recommendations, genomic testing is not routine in all PDAC patients (pts) in Australia, due to unproven clinical impact. As more novel KRAS-direct therapeutics enter clinical trials, understanding the real-world frequency of individual mutations and prognostic significance, and facilitating trial recruitment are important goals, all of which can be supported by registry data. Methods: Data extracted from the PURPLE pancreatic cancer registry from 9 participating Australian cancer centres, between 2016-2022, was analysed to compare clinicopathological features, survival based on KRASmt status, and assess feasibility of the platform to identify and molecularly stratify patients for future clinical trials. Survival estimates were calculated using Kaplan-Meier curves and log-rank testing on SPSS (Macintosh v.29). Results: Of 721 PDAC routine care pts identified, next generation sequencing (NGS) was undertaken in 378/721 (52%). Median patient age was 68 years (range 52-83); 152 (40%) had resectable, 111 (29%) locally advanced and 115 (30%) metastatic disease. 57/378 (15%) were KRAS wildtype. Of 321 pts with a KRAS mt, codons 12,13, and 61 were the most common sites of mt, including G12D (45%), and G12V (30%), with lower frequencies of G12R (13%), Q61H (6%), G12A (3%), G12C (1%), and G13D (1%). Comparing KRAS wildtype to KRASmt pts, there was no difference in median age (68 vs 67, p=0.63), gender (male: 49% vs 60%, p=0.23), Charlson comorbidity index (p=0.30), or stage at first presentation (p=0.99). Overall KRAS wildtype pts were more likely to be ECOG PS 0 at diagnosis (p=0.01) and to receive at least 1 modality of treatment (p=0.004). For all pts, median overall survival (OS) in KRASwildtype versus KRAS mt pts was 29.0 months versus 19.7 months (p=0.007), and for the 115 metastatic pts 15.1 versus 10.4 months (p=0.28). Further analysis of the impact by disease stage and by individual RAS mt is underway. Conclusions: Registry based analysis informs understanding of KRAS mt status of PDAC in a community setting. Here, KRAS mt status was associated with worse OS outcomes, likely in part due to the association with ECOG PS and receiving less active treatment. With newer promising KRAS-targeted therapies becoming available in clinical trials, known RAS status will aid identification of trial candidates. The clinical utility of NGS and rationale for reflex testing in PDAC is increasing. Clinical Registry information (ACTRN12617001474347).

Achieving a textbook outcome in patients undergoing gastric resections in a low incidence, high-volume Australian Upper GI unit

BackgroundTextbook outcome (TBO) has been proposed as a composite measure of quality in esophagogastric surgery, and achieving a TBO has been associated with improved overall survival (OS). The Dutch Upper Gastrointestinal Cancer Audit group determined their TBO rate for gastrectomy to be 32.1%, using 10 parameters. Our study aimed to assess the TBO rate in patients who had a gastrectomy for cancer in an Australian Upper GI unit, allowing for comparisons with international specialist centers. MethodsRetrospective analysis of a prospectively maintained database of patients who had a gastrectomy for cancer performed by the surgeons in a single Australian center between 2013 and 2018. Postoperative complications were analyzed using Clavien-Dindo (CD) ≥2 and CD ≥3 definitions. Baseline factors and their association with TBO were analyzed using multivariable logistical regression. The association between TBO and survival rates was determined by Cox proportional hazards regression analysis. ResultsIn 136 patients, 84 (62%) achieved a TBO when complications were graded as CD ≥2. Greatest negative impact on TBO was the complication rate, lymph node yield, and length of stay. Patients more likely to achieve a TBO were younger, with an increased body mass index and absence of underlying respiratory disease. A nonsignificant trend toward improved OS was seen when TBO was achieved. ConclusionOur TBO rate compares favorably with published data from high-volume centers. Assessment of a unit’s TBO may provide a stronger evaluation of quality when assessing where complex surgery should be performed within Australia.

The potential role of serial circulating tumor DNA (ctDNA) testing after upfront surgery to guide adjuvant chemotherapy for early stage pancreatic cancer: The AGITG DYNAMIC-Pancreas trial.

107 Background: Recurrence rates following upfront resection of pancreatic adenocarcinoma are high, with some benefit from adjuvant chemotherapy (AC). A biomarker that improves risk stratification and/or provides real time indication of AC benefit could improve routine clinical management and accelerate trial progress. Previous studies in pancreas cancer suggest that patients with detectable ctDNA post surgery are at an elevated risk of recurrence. Detectable ctDNA at the completion of AC may also be associated with an elevated recurrence risk. Methods: Patients with early stage pancreatic adenocarcinoma were enrolled following upfront resection at 26 Australian centres. Patients were ECOG 0-1 and fit for AC. A tumour-informed ctDNA assay was used to identify somatic mutations for tracking in circulating cell-free DNA. ctDNA+ patients received 6 months of AC (FOLFIRINOX or gemcitabine/capecitabine selected at the clinician's discretion), while ctDNA- patients could de-escalate to 3 months at the clinician’s discretion. ctDNA was assessed again at the end of AC. The primary study endpoint was the feasibility of ctDNA-guided therapy. Secondary endpoints included the association of ctDNA with clinicopathologic risk factors and survival outcomes. Results: A total of 102 patients were enrolled from March 2019 to Nov 2023. Median age was 68 years (range 41 – 86), with 50% male and 95% ECOG 0-1. Tumours were located in the head of pancreas in 72%. Histology revealed T1 (18%), T2 (50%), and T3 (32%) tumors, with nodal involvement in 71%, and an R0 resection in 77%. Post-operative Ca19-9 was elevated in 29%. Forty patients (40%) were ctDNA+ve post resection, 54 (53%) were ctDNA-ve, and no result was obtained in 4 (4%) due to the absence of tumor mutation, and as a result, they were considered ineligible. The presence or absence of ctDNA was not associated with known clinicopathologic risk factors. Median time to ctDNA collection was 5 weeks (range 3 – 9) and to commencing AC was 6 weeks (range 4-12). Of 54 ctDNA-ve patients, 24 (44%) were de-escalated to receive a planned 3 months of AC. With a median follow-up of 36 months (range 2-56) the median recurrence free survival (RFS) in ctDNA+ve patients was 13 months compared to 22 months for ctDNA-ve patients (HR 0.52, p = 0.003). Conclusions: A tumor informed ctDNA approach to AC selection is feasible for patients undergoing upfront resection of pancreatic adenocarcinoma, with the first blood draw to be scheduled at week 5, allowing time for ctDNA analysis to determine AC selection. A high proportion of patients had detectable ctDNA, which appears independent of known prognostic markers. ctDNA detection was associated with earlier recurrence. Analyses of the impact of changes in ctDNA over time on survival are ongoing. Clinical trial information: ACTN12618000335291.

Short-Term Surgical Outcomes of Dialysis-Dependent Renal Failure Patients Post Isolated Coronary Artery Bypass Grafting From 2013–2023 in a Single South Australian Centre

Short-Term Surgical Outcomes of Dialysis-Dependent Renal Failure Patients Post Isolated Coronary Artery Bypass Grafting From 2013–2023 in a Single South Australian Centre

Genomic analysis of Helicobacter pylori in Australia: Antimicrobial resistance, phylogenetic patterns, and virulence factors.

Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally, but little is known about contemporary resistance patterns, virulence factors, and phylogenetic patterns of isolates within Australia. We aimed to characterize antimicrobial resistance and genetic mutations associated with adverse clinical outcomes. Whole genome sequencing, culturing, and antibiotic sensitivity data for refractory H.pylori isolates at Australian centers were collected between 2013 and 2022. Phylogenetic origins, antibiotic resistance mutations, and virulence factors were examined with phenotypic resistance profiles. One hundred thirty-five isolates underwent culture, with 109 of these undergoing whole genome sequencing. Forty-three isolates were isolated from patients in South Australia and 66 from Western Australia. Isolates originated primarily from hpEurope (59.6%), hpEastAsia (25.7%), and hpNEAfrica (6.4%). Antimicrobial resistance to clarithromycin was seen in 85% of isolates, metronidazole in 52%, levofloxacin in 18%, rifampicin in 14%, and amoxicillin in 9%. Most isolates (59%) were multi-drug resistant. Resistance concordance between genetically determined resistance and phenotypic resistance was 92% for clarithromycin and 94% for levofloxacin. Analysis of virulence factors demonstrated cag pathogenicity island (cagPAI) in 67% of isolates and cagA in 61%, correlating with isolate genetic origin. The most virulent s1m1 vacuolating cytotoxin A genotype was present in 26% of isolates. Refractory H.pylori isolates in Australia emanate from multiple global origins. Strong concordance between genetic and phenotypic antibiotic resistance profiles raises the possibility of utilizing genetic profiling in clinical practice. The dynamic landscape of H.pylori in Australia warrants the establishment of a national database to monitor H.pylori resistance and evolving virulence.

A 10-year review of presentation, management and outcomes of STEMI in a high-volume regional tertiary Australian centre

ObjectiveTo assess the trends and impact of changes in management of ST Elevation Myocardial Infarction (STEMI) from 2010 to 2019. DesignRetrospective analysis of data from STEMI hospitalisations including demographic, comorbidity, angiographic and outcome data. Setting/participantsHigh-volume non-surgical regional Australian tertiary referral centre. Main outcome measurementsIndex & 12-month mortality (all-cause & cardiovascular), door-to-balloon time, target-vessel failure, target-vessel revascularisation & procedure-related bleeding. ResultsFrom 2010 to 2019, 1299 patients presented with STEMI. The cardiovascular risk factor profile did not significantly change over the 10-year study period, p = 0.23. There was a significant trend toward culprit vessel percutaneous coronary intervention with stenting, rather than balloon angioplasty followed by surgical revascularisation, p = 0.029. The mean door-to-balloon time was 88 +/− 5.7 min and demonstrated a statistically significant improvement across the decade, p = 0.035. Radial access became the preferred angiographic approach (2010 92% femoral, 2019 91% radial). Drug-eluting stents (DES) replaced bare metal stent use. There was a statistically significant reduction in 12-month cardiovascular mortality across the decade (p = 0.042). However index hospitalisation (cardiovascular and all-cause) and 12-month all-cause mortality did not reduce. Young patients and women are important sub-groups of STEMI presentations with different risk factor profile. ConclusionsAdvances in management of STEMI such as radial access, use of DES and a significant reduction in door-to-balloon time across the decade resulted in a reduction of 12-month cardiovascular mortality over the decade however there was no significant reduction in 12-month all-cause mortality, or index hospitalisation cardiovascular or index hospitalisation all-cause mortality. Further research is needed to ensure non-mortality outcomes, such as heart failure hospitalisation and quality of life, also demonstrate temporal improvement with STEMI management advances. Earlier cardiovascular risk assessment should be considered in smokers than is currently recommended in Australian guidelines (≥45yo for most individuals).

Redesigning antenatal care: Prospective use of an implementation framework to establish a population-based multidisciplinary first-trimester screening, assessment and prevention service.

Australian rates of adverse obstetric outcomes have improved little despite guidelines recommending history-based screening and intervention. The first trimester provides a unique opportunity to predict and prevent complications, yet population-based screening has failed to be translated into broad clinical practice. This study aimed to redesign antenatal care within an Australian public healthcare centre to align with evidence-based maternity care, including population-based first-trimester screening with early initiation of preventative strategies in high-risk pregnancies. A five-phase action-process model, sharing key elements with implementation science theory, was used to explore barriers to change in antenatal care, co-design a novel service with consumers and establish a population-based antenatal pathway commencing with a multidisciplinary first-trimester screening, assessment and planning visit. The case for change and associated barriers were defined from the perspective of antenatal care stakeholders. Key needs of each group were established, and solutions were created using co-design methodology, allowing the team to create a novel approach to antenatal care which directly addressed identified barriers. Implementation of the service was associated with a fall in the median gestation at first specialist maternity care provider visit from 20 to 13 weeks. This study confirms the feasibility of establishing a comprehensive first-trimester screening program within a public Australian healthcare setting and highlights a co-design process which places individualised assessment at the forefront of antenatal care. This framework may be applicable to most public maternity settings in Australia, with expansion aimed at providing equity of care, including in rural and remote settings.

Examining the impact of a group treatment using cognitive and social cognition remediation for young offenders: The justice health NSW school-link advantage pilot study.

Young offenders experience higher rates of neurodevelopmental and mental health disorders than the general population, and significant access barriers to health treatment. Treatment combining Cognitive Remediation Therapy (CRT) and Social Cognition Remediation Therapy (SCRT) has demonstrated benefits for functional improvements and social development. However, there is limited information regarding group treatment programs in custodial settings for young offenders. This pilot study explores the effectiveness and feasibility of a group treatment program for youth offenders with cognitive deficits and mental health concerns in youth detention. The School-Link Advantage pilot study designed and tested a 10-week group treatment program combining CRT and SCRT for young offenders in custody. The closed groups incorporated interactive activities focussed on emotional recognition and regulation skills, optimizing executive functioning, understanding values, exploring belief systems, improving relationships, and safety planning. Of the 22 male participants recruited in an Australian Youth Justice Centre, 12 completed all aspects of the treatment program, reflecting a 54.5% completion rate in a typically challenging to engage population cohort. Results demonstrated significant improvements in the ability to store and retrieve information, recognize information, and control emotions. Planning and organizing skills also showed considerable development. This pilot study suggests that a combined CRT and SCRT group treatment program has the potential to effectively target cognitive challenges associated with mental health disorders in young offenders in custody. These promising outcomes suggest exploring randomized controlled trials with increased cultural sensitivity for diverse populations.

The Clinical and Radiological Outcomes of the Multimodal Use of the Woven EndoBridge Device: A Large Multicenter Study

The Woven EndoBridge (WEB) is a device used for intrasaccular flow diversion, designed for the elimination of wide-necked bifurcation aneurysms from the circulation. In this study, we aim to assess the safety and efficacy of the WEB and its uses in treating aneurysms of different morphologies and locations. In a retrospective analysis, we compiled a comprehensive dataset from patients treated with the WEB device across three major Australian neurovascular centers from May 2017 to September 2023. The case series encompassed a spectrum of aneurysm types, including wide-necked bifurcation, sidewall, and irregularly shaped aneurysms, as well as cases previously managed with alternative therapeutic strategies. This study additionally encompasses cases where aneurysms were managed using the WEB device in combination with supplementary endovascular devices. The study included 169 aneurysms in 161 patients. The rate of satisfactory aneurysm occlusion was 85.6%, with 86.7% of patients maintaining good functional status at their most recent follow-up. The procedure exhibited a low mortality rate of 0.6% and a thromboembolic complication rate of 7.1% (n= 12/161). There were no instances of postoperative re-rupture and the procedure-related hemorrhage rate was low (1.2%, n= 2/169), aligning with the literature regarding the safety and efficacy of the WEB device. Our multicenter trial reinforces the WEB device's role as an effective and safe modality for intracranial aneurysm management, supporting its expanded application beyond wide-necked bifurcation aneurysms. Further prospective studies are required to delineate its evolving role fully.

Percutaneous triamcinolone injection for upper eyelid retraction in thyroid eye disease.

To evaluate percutaneous triamcinolone (TA) injection efficacy in treating upper eyelid retraction (UER) for Australian thyroid eye disease (TED) patients. We conducted a retrospective analysis across 8 years and multiple diverse Australian centres identified UER patients who received TA injections. A single operator administered 40mg/1ml TA through upper eyelid skin. Assessments at 4-6 weeks and subsequent eyelid measurements gauged treatment response and complications. 24 patients and 25 eyelids were included in the study. 91.6% were female, mean age 40.8 ± 10.3 years with mean follow-up of 17.5 months (± 18.5). Pre-treatment MRD1 was 6.2mm ± 1.4, and we observed a mean improvement of 2.2mm from pre-treatment to post-treatment (p<0.001). The mean UER measurement before treatment (defined as MRD1 - 4.0mm) was 3.0mm ± 1.3 (range, 0-6mm). After treatment, the mean UER measurement was -0.1mm. Quality of life (QOL) assessment improved significantly, from pre-treatment score of 4.13 ± 2.4 to post-treatment 8.0 ±1.7 (p<0.001). Percutaneous injection of TA is an effective and safe treatment option for UER in patients with TED. This technique can be performed without upper eyelid eversion, which makes it more tolerable for patients and less complex for the operator compared to the transconjunctival injection approach. Our results show a significant improvement in MRD1 and UER, as well as patient QOL. Moreover, we found a low rate of complications (4.2% induced ptosis) and no cases of raised intraocular pressure. Percutaneous TA injection can greatly reduce the need for eyelid lowering surgery in this patient population.

The Australian Hydrogen Centre – feasibility studies for achieving 10 and 100% renewable hydrogen in South Australia and Victoria

The Australian Hydrogen Centre (AHC) was established to deliver Australian-first feasibility studies into how existing natural gas distribution networks could be used in a system to produce, store, and transport renewable hydrogen, decarbonising gas supply while still meeting the needs of customers. The AHC Reports show that it is technically and economically feasible to use existing gas infrastructure for scaled hydrogen distribution, delivering: (1) net-zero carbon emissions gas; (2) minimised customer disruption while retaining security and diversity of supply; (3) services to the electricity grid through flexible electricity demand and frequency control; (4) 15 gigawatts (GW) of electrolysis supported by over 30 GW of new renewable electricity generation; (5) 30 petajoules (PJ) of hydrogen storage to harness the ability of gas to store vast amounts of energy, balancing renewable electricity supply and demand swings between colder and warmer months; and (6) over AU$1.5 billion in additional economic value a year including more than 12,500 jobs during construction and 6200 jobs during operation. Supported by a range of independent technical studies, the Reports provide a better understanding of the opportunity to access Australia’s world-class gas distribution infrastructure to unlock hydrogen opportunities while retaining energy security and affordability; identifying a range of low-regret enablers that could trigger coordinated action by government and industry. They also share learnings from Hydrogen Park South Australia (HyP SA), an Australian-first demonstration of hydrogen blending in a gas distribution network.