Jeff Szer

There is nothing permanent except change. Attributed to Heraclitus, 6th Century BCE. As I began by writing 12 months ago, change continues in so much of our professional lives and this is definitely seen to continue in 2024 in our journal, the Internal Medicine Journal (IMJ). Most directly we were affected by additional key resignations from the Editorial Board but enthusiastically have received new members of the Board in a process guided by the relevant specialist societies. Professor Velandai Srikanth, Geriatric Medicine editor since 2019, was replaced by his successor Associate Professor Paul Yates, Austin Health and University of Melbourne. Professor Janet Hardy, Palliative Medicine editor, with an impressive 18-year stay, was replaced by Professor Jennifer Philip, St Vincent's Hospital, Melbourne. Janet was particularly proactive in soliciting editorials. Her editorial on euphemisms1 (published in 2016) and promoting the usage of the word ‘death’ while avoiding the term ‘passing away’ has become part of our style manual. The specialty of Palliative Medicine placed a major emphasis on encouraging openness in discussions around death and making decisions around end-of-life care. Professor Christian Gericke, Public Health Medicine editor since February 2024, left a departing gift of a podcast on Pomegranate Health in August on the topic of readmissions. He was replaced by Associate Professor Phillip Hider from the University of Otago, Christchurch, New Zealand, in July. Phillip is an experienced public health physician who has also served on multiple committees of the Australasian Faculty of Public Health Medicine. Most recently, Dr Elizabeth Potter, Internal Medicine editor since February 2023, announced her resignation, given her competing substantive roles as unit director and chair of the IMSANZ research network. Her successor is yet to be confirmed. We welcome our new additions and thank those leaving for other ventures. No one has been unaffected by the rise of artificial intelligence (AI) models and systems. There were increasing submissions around this theme in 2024, notable as its impact on medicine and science remains fundamentally uncertain and its place in publishing still undefined. The editorial by Paul Komesaroff in the October 2024 issue of IMJ entitled ‘How should journals respond to the emerging challenges of artificial intelligence’2 makes a start at addressing the challenges this developing entity creates for us all. On your behalf, I attended the meeting of the Asia Pacific Association of Medical Journal Editors in Newcastle this year and this subject was a major topic of discussion, with many of the potential pitfalls being aired. The topic of AI authorship was discussed seriously and I am pleased to say that there was universal acknowledgement that AI, in any form, could not be a named author on a paper. IMJ was directly responsible in 2024 for two podcasts in the IMJ On-Air Series. In January, Paul Bridgman spoke in an episode entitled 'Is the jury out on Omega-3 supplementation', while in August, Christian Gericke discussed ‘Understanding readmissions better’. These podcasts are easily accessible by searching for ‘Pomegranate Health’ in Apple Podcasts, Spotify, Castbox or any podcasting app. You should probably do that now, before you forget where you read this. With the assistance of the College's official media group, Essential, there were multiple media releases on topics published in the Journal including notable ones on cancer in the prison population, indigenous Australians' access to medical care and prophylaxis for post-operative thromboembolic disease to reduce preventable deaths. Each of these releases is approved by the College President. Our social media presence continues to grow beyond X (@The_IMJ) to Bluesky (@the-imj.bsky.social) where we acquired over 330 followers in 1 month. So IMJ has far-reaching impact beyond the impact factor and the unique educative role we have, both for the readership and the broader community, is growing. Speaking of impact factor, ours was 1.8 in 2023. This is down a little from the previous year, but our CiteScore, which takes into account a 4-year window of citations, was up from 18.9 to 22.0. Full-text article views continue to rise annually and for 2023 is rapidly approaching 1 million. Readership ofIMJ is global with Australia, the United States and China being our top three readership locations. The most viewed article in the Wiley Online Library was once again that by our former Neurology Editor Peter Gates on the rule of 4 of the brainstem.3 This is a perennial favourite and has topped views for several years now. Next in line is a set of consensus guidelines on the treatment of invasive aspergillosis from 2021.4 This paper was also cited over 26 times. Interestingly, the top paper by Altmetrics score (this tracks online attention from sources such as social media, traditional media, online reference managers and more) was an older paper on a multicentre, randomised study of metoclopramide for intractable hiccups.5 Authors, reviewers and editors will see a major change in the software platform for 2025. Our original and evolved interface, ScholarOne is to be replaced by a Wiley-developed custom platform called Research Exchange Review, or ReX. This has already launched successfully in many journals in the Wiley stable and should have the advantage of system-wide consistency in article types while hopefully providing a user-friendly, intuitive and clear dashboard. Included will be integrated screening tools for ethics and integrity issues, journal scope match (a major source of headache for the editorial office) and language checks. To assist editors, smart reviewer selection tools should be a significant help. On the theme of change, this might be the biggest one to come to IMJ since electronic manuscript handling began a couple of decades ago. Again, please subscribe to the electronic table of contents, which will automatically include alerts to newly published papers and perhaps direct you to our app. Sign up at Wiley Online Library at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1445-5994 and click on the ‘Get New Contents’ alert tab in the upper left corner, or for Fellows of the RACP, via the publications link at http://www.racp.edu.au. Please explore this function if you have not done so already. I would like to express my usual but increasingly heartfelt thanks to our editorial board and reviewers for 2024. The names of the reviewers are tabulated after this piece. Of special acknowledgement are those 7 reviewers who reviewed the most papers in 2024, namely P. Pavli, F. Macrae, G. Hebbard, D. Holt, A. Pokorny, V. Limaye and M. Parker. The editors and their roles are always included in the first few pages of each edition of IMJ. Each of these unpaid volunteers makes essential contributions to IMJ. I would reiterate that the acceptance of an invitation to review a submitted manuscript is an essential part of scientific exchange and should be a duty not shirked, particularly by those who expect to have their own work peer-reviewed and published. To Virginia Savickis, Editorial Manager extraordinaire, and Louise Young-Wilson, Editorial/Technical Assistant, I express my personal and sincere thanks and admiration for an ongoing first-class job of getting each of our issues ready on time and maintaining such good contact with our editors and authors. So, I welcome you all, readers, writers and reviewers, to a hopefully safe, enjoyable and productive 2025 where there will doubtless be more change afoot. Many have noted that the College has advertised for expressions of interest in the Editor-in-Chief roles of this and our sister publication, the Journal of Paediatrics and Child Health. I would like to reassure all that this is a tightening of process and does not mean that either Ju-Lee Oei or I have immediate plans to do anything other than ensure the continued success of our respective journals.

Preimplantation genetic testing (PGT) is practiced worldwide, allowing the prevention of the transmission and expression of various genetic conditions. Socio-ethical considerations of justified applications for PGT are part of an ongoing debate. Pathogenic variants in the glucocerebrosidase (GBA1) gene, causing Gaucher disease (GD), have emerged as a risk factor for Parkinson's disease (PD) in both patients and carriers. Genotype-phenotype correlations exist between different GBA1 pathogenic variants and the risk to develop PD: mild pathogenic variants increase the risk of developing PD by ~3-fold, while severe pathogenic variants increase this risk by ~15-fold, occurring at a younger age. A woman with GD, a compound heterozygote of N370S (now commonly described as c.1226A>G (N409S)-mild pathogenic variant) and 84insG (severe pathogenic variant), had PGT consulting before planned in vitro-fertilization. Her mother, an 84insG carrier, had early-onset PD. GBA1 sequencing of her spouse was negative. We discussed the selection for N370S carrier embryos to reduce PD risk. This case report demonstrates the expansion of PGT for late-onset conditions. These novel indications will increase the number of subjects who would be candidates for PGT. The medical and bioethical considerations of these cases should be acknowledged by the professional community and discussed with couples during genetic counseling.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired non-malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients. Objective: This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab). Methods: Respective pivotal studies provided patient-level trial data for pegcetacoplan (16-week PEGASUS [NCT03500549]) and published data for iptacopan (24-week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient-reported outcomes on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis. Results: Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change-from-baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level (-0.49 g/dL [-1.78, 0.80]); ARC (-34.41 × 109/L [-90.02, 21.21]); LDH level (-115.16 U/L [-244.40, 14.01]); FACIT-Fatigue score (3.57 [-5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient-reported fatigue, providing similar point estimates and confidence intervals. Conclusions: This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient-reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease- and patient-related factors. Background: ClinicalTrials.gov identifier: NCT03500549.

Background: Elevated serum uric acid (SUA) levels were observed in Gaucher disease type 1 (GD1) patients followed for two decades in northern Israel. There are no previous reports regarding hyperuricaemia in GD1 patients. Objective: We aimed to evaluate the frequency of hyperuricaemia in GD1 patients and its correlation to disease severity, lymphoproliferative neoplasms and other malignancies. Methods: Clinical and laboratory data of 69 GD1 patients, 25 treatment-naïve and 44 on enzyme replacement therapy (ERT), were evaluated for SUA levels, biomarkers and the presence of lymphoproliferative neoplasms and other malignancies. Results: In 36 females and 33 males, the mean age was 51.6 ± 16.2 years, and the mean severity score index was 8.94. SUA levels were significantly higher in patients with severe disease compared to patients with mild disease. ERT had no significant effect on SUA levels. A linear correlation between SUA levels and disease severity was found. A linear correlation was also detected between acid phosphatase (AP) levels and SUA. Among patients with severe disease, 11% presented with a lymphoproliferative neoplasm, compared to 4% in patients with mild disease. A statistically significant difference in malignancy frequency between the two patient groups was not found. Conclusions: SUA levels are significantly elevated in severe GD1 patients and correlate with AP levels. AP was used in GD as a clinical biomarker, especially tartrate-resistant acid phosphatase, which reflects GD macrophage activity and inflammation status, thus associated with disease severity. No correlation between SUA levels and lymphoproliferative neoplasms was found. SUA levels may be helpful in estimating Gaucher cell burden and GD1 severity.

Relapse after allogeneic stem cell transplantation (alloSCT) represents a frequent complication in patients with myelofibrosis (MF). This retrospective study analysed 38 patients with JAK2-mutated MF who underwent alloSCT. Serial sensitive molecular assessments at regular intervals of JAK2 V617F revealed that a ≥2-fold increase in JAK2 variant allele frequency (VAF) at days +100 and +180 post-alloSCT was highly predictive of eventual morphological relapse. The integration of JAK2 VAF monitoring with chimerism analysis into post-alloSCT care represents a novel strategy for early detection of MF relapse, which may enable timely interventions and improve outcomes in such high-risk patients.

Complement Activation in the Lysosomal Storage Disorders