A lesion in two: Buruli ulcer and squamous cell carcinoma coexistence.

The concurrent diagnoses of Buruli ulcer (BU) and cutaneous squamous cell carcinoma (SCC) is a phenomenon not previously described, despite the fact that both conditions are highly prevalent in Australia. This report presents an intriguing case of concurrent diagnoses, with clues alluding to more than one skin condition being present. The case involves a 73-year-old man with BU diagnosed on the scalp, an atypical location, which led to the consideration of malignancy, ultimately revealing concurrent SCC. This case highlights the importance of considering both conditions in patients with epidemiological risk factors, necessitating multiple lines of investigation for accurate diagnosis. Medical practitioners must remain vigilant and incorporate this possibility into their diagnostic algorithms for suspicious skin lesions to optimize treatment and outcomes. This is the first recorded instance of simultaneous diagnosis, underlining the need for enhanced awareness and attention to these unique cases.

Use of targeted SMS messaging to encourage COVID-19 oral antiviral uptake in South West Victoria.

OBJECTIVES: During winter 2022, as part of a multifaceted approach to optimise oral antiviral uptake in the Barwon South West region in Victoria, Australia, the Barwon South West Public Health Unit (BSWPHU) implemented an innovative, targeted SMS messaging program that encouraged people with coronavirus disease 2019 (COVID-19) to be assessed for antiviral treatment. In this study, we investigated patterns of antiviral uptake, identified barriers and facilitators to accessing antivirals, and examined the potential impact of targeted SMS messaging on oral antiviral uptake. METHODS: We conducted a cross-sectional study of notified COVID-19 cases aged 50 years and older, and Aboriginal and Torres Strait Islander people aged 30-49 years, in the BSWPHU catchment area over a 6-week period commencing 21 July 2022. We analysed survey data using descriptive statistics and generalised linear models. RESULTS: Of the 3829 survey respondents, 36.7% (95% confidence interval (CI) 35.2, 38.2) reported being prescribed oral antivirals, with 75.4% (95% CI 72.8, 77.9) of these aged ≥70. Antiviral prescriptions increased significantly over the 6-week survey period. Most prescriptions (87.5%; 95% CI 85.7, 89.2) were provided by the respondents' usual general practitioners (GPs). Barriers to receiving antivirals included respondents being unable to get a medical appointment in time (3.7%; 95% CI 3.1, 4.2), testing too late in their illness (2.3%; 95% CI 1.8, 2.8) and being unable to access medications in time after receiving a prescription (0.2%; 95% CI 0.1, 0.6). Facilitators to receiving antivirals included respondents first hearing about antivirals from a trusted source such as a family member, friend or usual doctor. Nearly one in eight people who were prescribed antivirals reported first hearing about them from the SMS message sent by BSWPHU. CONCLUSIONS: Oral antiviral treatment uptake in south-west Victoria in July-August 2022 was high among survey respondents and increased over time. GPs were the key prescribers in the community. Targeted SMS messaging to COVID-19 cases is a simple, low-cost intervention that potentially increases antiviral uptake.

Approach to diagnostic evaluation and prevention of invasive fungal disease in patients prior to allogeneic hematopoietic stem cell transplant.

In recent years, advancements in the treatment landscape for hematological malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia, have significantly improved disease prognosis and overall survival. However, the treatment landscape is changing and the emergence of targeted oral therapies and immune-based treatments has brought forth new challenges in evaluating and preventing invasive fungal diseases (IFDs). IFD disproportionately affects immunocompromised hosts, particularly those undergoing therapy for acute leukemia and allogeneic hematopoietic stem cell transplant. This review aims to provide a comprehensive overview of the pretransplant workup, identification, and prevention of IFD in patients with hematological malignancy. The pretransplant period offers a critical window to assess each patient's risk factors and implement appropriate prophylactic measures. Risk assessment includes evaluation of disease, host, prior treatments, and environmental factors, allowing a dynamic evaluation that considers disease progression and treatment course. Diagnostic screening, involving various biomarkers and radiological modalities, plays a crucial role in early detection of IFD. Antifungal prophylaxis choice is based on available evidence as well as individual risk assessment, potential for drug-drug interactions, toxicity, and patient adherence. Therapeutic drug monitoring ensures effective antifungal stewardship and optimal treatment. Patient education and counselling are vital in minimizing environmental exposures to fungal pathogens and promoting medication adherence. A well-structured and individualized approach, encompassing risk assessment, prophylaxis, surveillance, and patient education, is essential for effectively preventing IFD in hematological malignancies, ultimately leading to improved patient outcomes and overall survival.

First-in-human phase I/Ib study of NIZ985, a recombinant heterodimer of IL-15 and IL-15Rα, as a single agent and in combination with spartalizumab in patients with advanced and metastatic solid tumors.

BACKGROUND: Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody, in patients with advanced solid tumors. METHODS: This phase I/Ib study had two dose-escalation arms: single-agent NIZ985 administered subcutaneously thrice weekly (TIW, 2 weeks on/2 weeks off) or once weekly (QW, 3 weeks on/1 week off), and NIZ985 TIW or QW administered subcutaneously plus spartalizumab (400 mg intravenously every 4 weeks (Q4W)). The dose-expansion phase investigated NIZ985 1 µg/kg TIW/spartalizumab 400 mg Q4W in patients with anti-PD-1-sensitive or anti-PD-1-resistant tumor types stratified according to approved indications. The primary objectives were the safety, tolerability, and the maximum tolerated doses (MTDs) and/or recommended dose for expansion (RDE) of NIZ985 for the dose-expansion phase. RESULTS: As of February 17, 2020, 83 patients (median age: 63 years; range: 28-85) were treated in dose escalation (N=47; single-agent NIZ985: n=27; NIZ985/spartalizumab n=20) and dose expansion (N=36). No dose-limiting toxicities occurred nor was the MTD identified. The most common treatment-related adverse event (TRAE) was injection site reaction (primarily grades 1-2; single-agent NIZ985: 85% (23/27)); NIZ985/spartalizumab: 89% [50/56]). The most common grade 3-4 TRAE was decreased lymphocyte count (single-agent NIZ985: 7% [2/27]; NIZ985/spartalizumab: 5% [3/56]). The best overall response was stable disease in the single-agent arm (30% (8/27)) and partial response in the NIZ985/spartalizumab arm (5% [3/56]; melanoma, pancreatic cancer, gastric cancer). In dose expansion, the disease control rate was 45% (5/11) in the anti-PD-1-sensitive and 20% (5/25) in the anti-PD-1-resistant tumor type cohorts. Pharmacokinetic parameters were similar across arms. The transient increase in CD8+ T cell and natural killer cell proliferation and induction of several cytokines occurred in response to the single-agent and combination treatments. CONCLUSIONS: NIZ985 was well tolerated in the single-agent and NIZ985/spartalizumab regimens. The RDE was established at 1 µg/kg TIW. Antitumor activity of the combination was observed against tumor types known to have a poor response to ICIs. TRIAL REGISTRATION NUMBER: NCT02452268.

Insights into the Evolution of P. aeruginosa Antimicrobial Resistance in a Patient Undergoing Intensive Therapy.

Whole genome sequencing (WGS) provides insights into the evolution of antimicrobial resistance, an urgent global health threat. Using WGS, we observe evolutionary adaptation of a Pseudomonas aeruginosa strain within an immunocompromised patient undergoing antibiotic therapy. Two blood isolates (EA-86 and EA-87) from the patient evolved separate adaptations for antibiotic resistance, while sharing common adaptive mutations for host immune evasion. In EA-86, a silencing mutation in the antibiotic efflux pump repressor, NfxB, increased antibiotic resistance, while in EA-87, a similar mutation was seen in the antibiotic efflux pump repressor mexR. The number of genomic variants between the two isolates give a divergence time estimate of the order of 1000 generations. This time is sufficient for a bacterial lineage to have evolved an SNP in every position in the genome and been fixed if advantageous. This demonstrates the evolutionary adaptive power accessible to bacteria and the timescale for a brute-force functional survey of the SNP fitness landscape.

Healthcare worker access to molnupiravir: A case series.

Molnupiravir, an oral antiviral shown to reduce COVID-19 severity, is available in Australia via the Pharmaceutical Benefits Scheme (PBS) for treatment of mild-moderate COVID-19. For people less than 70 years of age it is only available with risk factors for severe disease, hence the majority of healthcare workers do not qualify. Currently, Australian health services are under considerable strain due to COVID-related staff shortages. Thirty staff members of a tertiary hospital, not eligible under the PBS, were offered molnupiravir within the first five days of COVID-19 illness. Their median age was 43 years, and 73% were female. All completed treatment with rates of adverse events that were low and comparable with clinical trial data. The reported duration of illness ranged from 1-16 days with a median of four days. A negative rapid antigen test on the final day of treatment was reported in 81% of people, and 73% reported being well enough to return to work at the completion of mandatory isolation. Only 22% of people reported transmission in their household after they commenced treatment. The implementation of a policy allowing access to molnupiravir outside of PBS recommendations for healthcare workers with mild-moderate COVID-19 may have important individual benefits to workers health and wellbeing and help alleviate the acute staff shortages experienced currently by the Australian healthcare workforce.