Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.

Cancer Nursing Frameworks to Guide Clinical Capability, Education and Careers: A Scoping Review of the International Literature.

Aim: This review aimed to provide a current global profile of all existing cancer nursing competency, capability, education and career frameworks and map capabilities and competencies to the clinical, facilitation of education, management and research pillars of practice.

Design: Scoping review.

Data Sources: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Epistemonikos, Google Scholar, Medline, and PubMed.

Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes.

The role of the microbiome in immune checkpoint inhibitor colitis and hepatitis.

Immune checkpoint inhibitors have revolutionised management for a variety of different types of malignancies. However, gastrointestinal adverse effects, in particular colitis and hepatitis, are relatively common with up to 30 % of patients being affected. The gut microbiome has emerged as a potential contributor to both the effectiveness of immune checkpoint inhibitors and their side effects.

How often are patients recording their healthcare consultations in Australia and why? An online survey.

Purpose: Recording important healthcare consultations can benefit patients. Technological developments enable recordings by patients and health professionals, as well as real-time 'listening' by AI scribes. Not enough is known about whether and why patients record their consultations.

Recent and Future Developments in the Use of Poly (ADP-ribose) Polymerase Inhibitors for Prostate Cancer.

Background And Objective: Advanced prostate cancer (PCa) is enriched for alterations in DNA damage repair genes; poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a class of drugs that have demonstrated effectiveness in PCa, particularly in tumors with alterations in BRCA1/2 and other homologous recombination repair (HRR) genes, acting through a synthetic lethal mechanism. To prevent or delay drug resistance, and to expand the patient population that can benefit from this class of drug, combination treatment strategies have been developed in preclinical and clinical studies.

Methods: This review examines the latest developments in clinical trials testing PARPi for advanced PCa and their emerging role in earlier disease settings.

Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Purpose: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited.

Methods: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion.

Lutetium-177-prostate-specific membrane antigen therapy for prostate cancer: current status and future prospects.

Purpose Of Review: Lutetium-177-prostate-specific membrane antigen (Lu 177-PSMA) radioligand therapy has emerged as a promising novel strategy for advanced prostate cancer. With its increasing importance alongside with a plethora of exciting results from latest trials, we would like to summarize current evidence and advancements in Lu 177-PSMA therapy across different stages of prostate cancer.

Recent Findings: In metastatic castration-resistant prostate cancer (mCRPC), early studies like the LuPSMA trial and TheraP trial demonstrated promising PSA response rates.

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?

Aims: To examine the associations between and polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.

Patients & Methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.

Compassionate access to virus-specific T cells for adoptive immunotherapy over 15 years.

Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with "off-the-shelf" allogeneic T cells directed to a combination of Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration's Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder.

Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study.

While HIV infection and clonal hematopoiesis (CH) have been linked with inflammatory dysregulation and an increased risk of aging-related comorbidities, their relationship with clinical geriatric syndromes has not been well defined. In the Age-related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE) study (NCT04641013), we measure associations between HIV and CH and geriatric syndromes. Of 345 participants (176 with HIV and 169 without HIV), 23% had at least one mutation associated with CH: 27% with HIV and 18% without HIV (p = 0.

Co-design of an electronic patient-reported outcome symptom monitoring system for immunotherapy toxicities.

Background: Utilising electronic patient-reported outcomes (ePRO) to monitor symptoms can improve patient outcomes. However, ePRO systems are typically not co-designed with end-users which may limit their utility and long-term sustainability. We aimed to co-design a real-time ePRO symptom monitoring system for immune checkpoint inhibitor (ICI) toxicities.

Application of Artificial Intelligence in Symptom Monitoring in Adult Cancer Survivorship: A Systematic Review.

Purpose: The adoption of artificial intelligence (AI) in health care may afford new avenues for personalized and patient-centered care. This systematic review explored the role of AI in symptom monitoring for adult cancer survivors.

Methods: A comprehensive search was performed from inception to November 2023 in seven bibliographic databases and three clinical trial registries.

Home-Based Exercise and Self-Management After Lung Cancer Resection: A Randomized Clinical Trial.

Importance: Patients with lung cancer have poor physical functioning and quality of life. Despite promising outcomes for those who undertake exercise programs, implementation into practice of previously tested hospital-based programs is rare.

Objective: To evaluate a home-based exercise and self-management program for patients after lung resection.

Emerging concepts of CMV in transplantation.

Cytomegalovirus (CMV) infections continue to be associated with significant morbidity and mortality following solid organ transplantation and haemopoietic stem cell transplantation. Advances in understanding the biology of CMV in the immunosuppressed host will translate into improved management approaches and better clinical outcomes. Updated definitions of resistant and refractory CMV infections will lead to more consistent reporting of CMV outcomes, better inform appropriate antiviral strategies and influence clinical trial design.

Operative management and outcomes of gallbladder cancer in Australia: a multi-institutional, retrospective, observational cohort analysis.

Background: Data on optimal extent of resection for various stages of gallbladder cancer are lacking. This study aims to evaluate disease-free (DFS) and overall survival (OS) after simple (SC) versus radical cholecystectomy (RC) for gallbladder cancer in the Australian context, and assesses factors associated with post-operative morbidity.

Methods: Multi-centre, retrospective cohort analysis including all gallbladder cancer patients who underwent resection across six Australian institutions between January 2010 and January 2020.

Choice of activation protocol impacts the yield and quality of CAR T cell product, particularly with older individuals.

Objectives: In clinical chimeric antigen receptor (CAR) T cell therapy, one of the strongest correlates of favorable patient responses is lower levels of differentiation in T cells from the peripheral blood mononuclear cell (PBMC) starting material or the CAR T cell product. T cells from older patients are inherently more differentiated, but we hypothesised that specific activation protocols could be used to limit CAR T cell differentiation during manufacturing, particularly in older patients.

Methods: We used PBMCs from young (20-30 years old) and older (60+ years old) healthy donors to generate CAR T cells using two activation protocols: soluble anti-(α) CD3 monoclonal antibody (mAb) immune complexes of αCD3 and αCD28 mAbs.

Daily fluctuations in adolescents' sleep predict next-day attention, sleepiness, and fatigue: an ecological momentary assessment study over 28 days.

Background: Current understanding of the associations between adolescents' daily sleep and daytime alertness and fatigue under naturalistically occurring restricted (school) and unrestricted (vacation) sleep opportunities is limited.

Methods: A convenience sample of adolescents (n = 205; 54.1% females, M ± SD = 16.

Antifungal stewardship in Australian hospitals: defining the scope and future targets.

Background: Antimicrobial stewardship (AMS) guidelines now recommend antifungal stewardship (AFS) interventions to improve the management of invasive fungal diseases (IFDs). AFS programmes have not been reported in Australia.

Aims: To determine the monitoring of antifungal use, AFS strategies and targets, and barriers to AFS implementation in Australian hospitals.