Search

Background: Brain metastases (BMs) occur in 20% to 40% of patients with METex14 skipping NSCLC.1--4 As part of the multidisciplinary teams that manage cancer patients, oncology nurse navigators play a key role in optimal patient management strategy. In the phase 2 VISION study, tepotinib, a once-daily and highly selective MET tyrosine kinase inhibitor, demonstrated an objective response rate (ORR) of 50.8% and a median duration of response (mDOR) of 18.0 months in patients with METex14 skipping NSCLC (NCT02864992; Cohorts A+C, N = 313).5 Objective: To provide analysis of the intracranial activity of tepotinib in patients with METex14 skipping NSCLC with BM from the VISION study to aid oncology nurse navigators who manage this population of patients. Methods: Patients with METex14 skipping NSCLC received oral tepotinib 500 mg once daily (450 mg active moiety). Patients with BM (asymptomatic and symptomatic/stable) were eligible. The primary end point was systemic ORR by an independent review committee (RECIST v1.1, accounting for both intra- and extracranial lesions); a subgroup analysis in patients with BM was predefined (data cutoff: February 20, 2022). An exploratory analysis of brain lesions was conducted by an independent review using RANO-BM criteria. Responses were determined in patients with ≥1 evaluable postbaseline tumor assessment. For those with only nontarget lesions (NTLs) per RANO-BM (enhancing and nonenhancing NTLs), disease control was defined as at least noncomplete response/nonprogressive disease. Results: Fifty-seven patients had baseline BM (Cohorts A+C, n = 313). Systemic ORR was 56.1% (95% CI, 42.4- 69.3), and mDOR was 9.0 months (95% CI, 5.6-not estimable [ne]). Forty-three patients were evaluable by RANO-BM, 30 (69.8%) of whom received prior brain radiotherapy or surgery. Twenty-three patients were treatment-naive, and 20 patients had received prior therapy lines. Overall intracranial disease control rate was 88.4% (95% CI, 74.9-96.1) with an intracranial progression-free survival of 20.9 months (95% CI, 5.7-ne). Fifteen patients had target BM lesions. Intracranial best objective responses were complete responses in 3 patients and partial responses in 7 patients; 3 patients had stable disease and 2 had progressive disease. Overall, intracranial ORR in patients with target lesions was 66.7% (95% CI, 38.4-88.2) with an intracranial DOR of ne (95% CI, 0.9-ne). Conclusions: In summary, the MET tyrosine kinase inhibitor tepotinib showed robust systemic activity in patients with METex14 skipping NSCLC with BM. In addition, tepotinib demonstrated promising intracranial activity in an exploratory analysis conducted using RANO-BM criteria. These results will not only inform practitioners in clinical decision-making but also oncology nurse navigators responsible for optimizing the treatment experience of patients with METex14 skipping NSCLC with BM. Industry sponsor: The healthcare business of Merck KGaA, Darmstadt, Germany. [ABSTRACT FROM AUTHOR]

Background: Cardiac screening of elite athletes is widely recommended by Australasian sporting federations, but data are not structured to be shared. Data are lacking from underrepresented groups to inform ECG interpretation guidelines. The ARENA (Australasian Registry of Screening ECGs in National Athletes) project is a retrospective and prospective, multicenter, longitudinal, observational registry of athlete cardiac screening results and outcomes. The aim is to create a repository to improve our understanding of the diagnoses and outcomes of screening., Methods: Participating sports that conduct cardiac screening of athletes will contribute data. This includes an initial collection (retrospective data, waiver of consent) and future prospective data (opt-out consent). Data include sex, age, sport/event, screening date, ECG findings, cardiac test results, follow-up details, sport participation status, cardiac diagnoses, and major cardiovascular outcomes defined as sudden cardiac arrest/death, cardiac syncope or implanted cardioverter defibrillator shock, cardiac hospitalization, and arrhythmias requiring intervention. Comparisons will be made between diagnoses, outcomes, and ECG features and analyzed by sport and sex. The ARENA project was developed in collaboration with sporting bodies, team physicians, and players association representatives and endorsed by the Australasian College of Sport & Exercise Physicians and Sports Medicine Australia., Conclusions: The ARENA project will provide a long-term international data repository to improve our understanding of ECG interpretation, cardiac screening and diagnoses, and the prevalence of cardiovascular outcomes in screened athletes. A unique aim is to address evidence gaps in underrepresented athlete groups, specifically female athletes and Indigenous populations. Results will inform screening policies and guidelines.

Pandemic-related business interruption (BI) losses are generally considered 'uninsurable' because, in order to pool sufficient premium revenue to meet valid claims, premiums would be unaffordable for the majority of policyholders. This paper explores whether and how such losses might be made insurable in the U.K. The authors consider post-pandemic governmental responses, including the role of the Financial Conduct Authority (FCA) and the meaning and implications of FCA v Arch Insurance (U.K.) Ltd ([2021] UKSC 1). The central premise of the paper is to highlight the importance of reinsurance in increasing an underwriter's insuring capacity and to illustrate how, with the support of government in the form of a public-private partnership (PPP), 'uninsurable' risks of this type may be made insurable. The authors propose a PPP, 'Pandemic Business Interruption Re', which provides, in their view, a feasible and defensible solution that would confer the benefit of increasing policyholders' faith in the industry's ability to underwrite pandemic-related BI claims and reduce reliance on ex post government aid., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Geneva Association 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The East Timor Hearts Fund has provided cardiac services in Timor-Leste since 2010, conducting three clinics yearly., Aim: To develop collaborative telehealth services between Australia and Timor-Leste in the context of international border closures due to the COVID-19 pandemic., Methods: Scoping discussions identified major challenges (structural, patient related and medical system related). At two pilot clinics, patient history, investigation and management were collated. Clinic metrics were compared with an index face-to-face clinic in February 2019. Post-clinic discussions identified areas of success and shortfall in the conduct of the telehealth clinics., Results: Twenty-three patients were reviewed at the online telehealth clinics held onsite at Timorese medical facilities. Compared with an index 2019 clinic, there were markedly lower numbers of new referrals (2 vs 190 patients; 8.7% vs 59.4%). Patients seen at the online clinic were predominantly female (17/23; 73.9%) and Dili based (18/23; 78.3%), with a mean age of 25.9 ± 7.2 years. The majority (12/23; 52.2%) had isolated rheumatic mitral valve disease. Investigations including electrocardiography, pathology, echocardiography and 6-min walk tests were conducted in select patients. Medication advice was provided for 10 (43.5%) patients. Eleven (47.8%) patients were deemed to require urgent intervention. Post-clinic discussions indicated general satisfaction with telehealth clinics, although frustration at the current inability to provide interventional services was highlighted., Conclusion: Our pilot telehealth clinics indicate that capacity-building telemedicine can be rapidly implemented in an emergency setting internationally. Clinic design benefits from careful identification and resolution of challenges to optimise flow. Cardiac patients in Timor-Leste have a significant burden of disease amenable to intervention., (© 2022 Royal Australasian College of Physicians.)

Background: The East Timor Hearts Fund (ETHF) is a charitable organisation of Australian cardiologists providing outreach screening in Timor-Leste. For patients requiring intervention, ETHF arranges logistics, procedures, and postoperative care. The aim of this project is to evaluate outcomes of patients requiring intervention., Methods: The ETHF database of all patients was utilised to identify patients with disease warranting surgical or percutaneous intervention. Both patients who underwent intervention and those who did not proceed to intervention were included in this study. Patients who had intervention arranged by other organisations but have then had follow-up with ETHF were also included. Overall demographics and pre and postoperative factors were assessed, with sub-group analysis of adult and paediatric patients to identify any differences in care., Results: Of 221 patients requiring intervention, 101 patients underwent intervention, receiving 22 different operations or procedures. Patients were predominantly young (median age 17.5 years) and female (64.7%), with rheumatic heart disease (63.8%). Twenty-four (24) (33.3%) women aged 15-45 years old with cardiac disease warranting intervention were documented as pregnant or breastfeeding at time of clinic assessment. Of patients who did not proceed to intervention, adults were more likely to be lost to follow-up (42.4% vs 18.5%) while paediatric patients were more likely to experience progression of disease (18.5% vs 7.5%, p=0.005). Median waitlist time was 5 months, with no significant difference between adults and children, correlating with a preoperative mortality rate of 5.4%. For patients who underwent intervention, post-procedure mortality was extremely low (0.9%) and attendance of at least one post-procedure review was excellent (99.0%). Eleven (11) (10.9%) patients have required repeat intervention, with no difference in rates between adult and paediatric patients. Length of follow-up extends up to 20 years for some patients., Conclusion: The Timor-Leste interventional cohort was predominantly a young female population with rheumatic and congenital cardiac disease. There were also high rates of pregnancy amongst female patients with severe cardiac disease. Delayed access to intervention may result in preoperative adverse events and mortality, and is a key target for improvement. Patients who undergo intervention have very low post-procedural mortality, good adherence to early medical follow-up and good long-term outcomes., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Background: Timor-Leste is one of the poorest countries in the world. The East Timor Hearts Fund is a charitable organisation involving Australian cardiologists providing outreach screening and access to cardiac interventions., Aims: To assess ten years of clinical volume, demographics and patient outcomes. Our intention was to identify existing limitations to facilitate planning for further capacity building over the next decade., Methods: The East Timor Hearts Fund database was sectioned into 2-year intervals (2009/2010, 2011/2012, 2013/2014, 2015/2016 and 2017/2018). Demographics and clinical outcomes of patients were compared, with subgroup analysis of adult (>18 years old), paediatric and interventional patients., Results: Over 10 years, 2050 patient encounters have occurred; 1119 (54.6%) encounters occurred in 2017/2018; 73.6% of patients were assessed in the capital Dili. Rheumatic and congenital cardiac diseases remain very common (39.1% of adult new patients and 74.2% of paediatric new patients), with 1.4% of new patients exhibiting both pathologies. The number of new patients with rheumatic or congenital heart disease tripled in 2017/2018 compared to 2009/2010 (99 vs 34 patients, P < 0.0001). Paediatric case volume increased over 10-fold over 10 years (288 new patients in 2017/2018 vs 24 in 2009/2010, P < 0.0001), with corresponding increase in proportion of paediatric interventions (59.4% in 2017/2018 vs 25.0% in 2009/2010, P = 0.027). For patients undergoing intervention (n = 87), post-procedural complications and mortality are extremely low (3.4% and 1.1%, respectively), with all eligible patients attending at least one post-procedure appointment., Conclusion: Demand for cardiac services in Timor-Leste is rising exponentially, with inequitable geographic coverage. Rheumatic and congenital cardiac diseases remain priorities for assessment, and paediatric case volume is increasing. Patients undergoing intervention experience good medical outcomes., (© 2019 Royal Australasian College of Physicians.)

Coronary CT angiography (CCTA) is a rapidly evolving technology which can characterise and image sub clinical atherosclerotic plaque and visualise anatomy and quantitate stenosis. Concern about radiation exposure has limited the uptake of this technology. The aim of this study was to review the radiation dose data in 2298 consecutive patients referred to a single centre in an Australian outpatient setting over 27 months using all available radiation dose reduction strategies. Prospective ECG gating ("step and shoot") was used preferentially in 2025 patients with a mean effective dose of 3.39 ± 1.84 mSv (range 0.86-12.6 mSv). For clinical reasons only 273 patients required retrospective ECG gating, mean dose 19.21 ± 5.58 mSv (range 2.4-34.9 mSv) resulting in an 85.7% reduction in dose for the majority of patients with the low dose technique. In conclusion, most patients referred for routine CCTA can be studied with a radiation dose comparable to invasive X-ray angiography and less than radionuclide myocardial perfusion imaging., (Copyright © 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.)

Background: Field cancerization is a feature of head and neck squamous cell carcinoma. No biological marker in the index tumour has been correlated to the development of second primary tumours (SPT). Cyclin A1 is a cell cycle regulator and a downstream target of p53. This study assessed predictive correlation of cyclin A1 and mut-p53 with clinicopathological parameters and occurrence of (SPT) in the head and neck., Methods: Using immunohistochemistry 106 patients treated for primary laryngeal squamous cell carcinoma were investigated for expression of cyclin A1 and mut-p53., Results: Expression of cyclin A1 and mut-p53 were noted in 83 of 106 (78.3%) and 25 of 106 (23.6%) patients. There was a weak but significant correlation between mut-p53 and cyclin A1 (r = 0.301, P = 0.002) expression. During the follow-up period (median 41.0 months (range 1-205 months)), 21 of 106 (19.8%) patients developed an SPT. There was no statistically significant correlation between the markers investigated and disease recurrence, SPT diagnosis or clinicopathological parameters., Conclusion: Second primary tumours are an intriguing problem in treatment of HNSCC and a predictive marker identifying those greatest at risk would be a leap forward.

A 76-year-old woman presents with acute pulmonary oedema and cardiogenic shock 10h after elective electrical cardioversion for atrial fibrillation. Her echocardiogram shows new wall motion abnormalities with akinesis of the apical and mid segments of the left ventricle and her resting ECG contains deep T wave inversion and QTc prolongation. Angiography reveals non-occlusive coronary artery disease. The echocardiogram on day 6 shows resolution of left ventricular wall motion abnormalities and a return to normal systolic function. The diagnosis of tako-tsubo cardiomyopathy was made. This is the first report of this condition precipitated by electrical cardioversion.

The extracellular matrix (ECM) is a reservoir of cellular binding proteins and growth factors that are critical for normal cell behavior, and aberrations in the ECM invariably accompany malignancies such as prostate cancer. Carcinomas commonly overexpress macrophage inhibitory cytokine 1 (MIC-1), a proapoptotic and antitumorigenic transforming growth factor-beta superfamily cytokine. Here we show that MIC-1 is often secreted in an unprocessed propeptide containing form. It is variably processed intracellularly, with unprocessed forms being secreted from several tumor lines, including prostate carcinoma lines, PC-3 and LNCaP. Once secreted, only unprocessed proMIC-1 binds ECM, demonstrating for the first time the occurrence of extracellular stores of MIC-1. The propeptide mediates this association via its COOH-terminal 89 amino acids. Xenograft models bearing tumors secreting various engineered forms of MIC-1 show that the propeptide regulates the balance between ECM stores and circulating serum levels of mature MIC-1 in vivo. The absence of propeptide results in approximately 20-fold increase in serum MIC-1 levels. The significance of stromal MIC-1 stores was evaluated in prostate cancer tissue cores, which show major variation in stromal levels of MIC-1. Stromal MIC-1 levels are linked to prostate cancer outcome following radical prostatectomy, with decreasing stromal levels providing an important independent predictor of disease relapse. In low-grade localized prostate cancer (Gleason sum score < or = 6), the level of MIC-1 stromal stores was the best predictor of future relapse when compared with all other clinicopathologic variables. The secretion and ECM association of unprocessed proMIC-1 is likely to play a central role in modulating local bioavailability of MIC-1 which can affect patient outcome in prostate cancer and other epithelial tumors.