Biomarkers for immunotherapy resistance in non-small cell lung cancer.

Immunotherapy has revolutionised the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving survival outcomes and offering renewed hope to patients with advanced disease. However, the majority of patients experience limited long-term benefits from immune checkpoint inhibition (ICI) due to the development of primary or acquired immunotherapy resistance. Accurate predictive biomarkers for immunotherapy resistance are essential for individualising treatment strategies, improving survival outcomes, and minimising potential treatment-related harm.

Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia.

Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube.

The role of C-reactive protein and ferritin in the diagnosis of HLH, adult-onset still's disease, and COVID-19 cytokine storm.

Cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), Adult-onset Still's disease (AOSD), and COVID-19 cytokine storm (CCS) are characterized by markedly elevated inflammatory cytokines. However clinical measurement of serum cytokines is not widely available. This study examined the clinical utility of C-reactive protein (CRP) and ferritin, two inexpensive and widely available inflammatory markers, for distinguishing HLH from AOSD and CCS.

Larger reductions in blood pressure during post-exercise standing, but not middle cerebral artery blood velocity, in resistance-trained versus untrained individuals.

Dynamic resistance exercise (RE) produces sinusoidal fluctuations in blood pressure, with hypotension and cerebral hypoperfusion commonly observed immediately following RE. Whether the cerebral vasculature adapts to these regular blood pressure challenges is unclear. This study examined the cerebrovascular response to post-dynamic RE orthostasis.

Case report: A novel third-generation anti-CD19/CD22 CAR T-cells combined with auto-HSCT for relapsed Burkitt lymphoma.

This study explores a novel therapeutic strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL) by integrating autologous hematopoietic stem cell transplantation (ASCT) with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T cell therapy. A 20-year-old Asian male with refractory BL, whose lymphoma had not responded to multiple chemoimmunotherapy regimens, received myeloablative ASCT followed three days later by infusion of a novel third-generation CAR T cells engineered with CD28 and CD3ζ signaling domains, along with a TLR2 costimulatory domain. This resulted in sustained complete remission at the 306-day follow-up, without experiencing any severe complications.

Posterior Reversible Encephalopathy Syndrome Associated With a Pontine Lacunar Infarct in a Severely Hypertensive Patient: A Case Report.

Posterior reversible encephalopathy syndrome (PRES) is a neurologic condition defined by symptoms and imaging findings secondary to vasogenic edema in the brain. Even though not all hypertensive individuals will progress to PRES, high blood pressure is the most frequent risk factor associated with the condition. The pathophysiology of PRES is not clearly understood, but the most accepted proposed mechanism focuses on the brain's inability to regulate cerebral blood flow through constriction or dilation of vessels during extreme blood pressure.

Challenges and consensus: A survey of the management of neonatal hypoglycaemia within the Pacific Islands.

Aim: To describe the management of neonatal hypoglycaemia within Pacific Island countries and territories by surveying practising clinicians.

Methods: Survey questions were adapted from a similar survey conducted across Australian and New Zealand neonatal nurseries. An anonymous, electronic survey link and QR code were disseminated to clinicians via our partner organisations, Facebook and direct email.

Hypercoagulation after Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study.

Background & Aims: Venous thromboembolism is a serious complication during and following hospitalization with acute severe ulcerative colitis (ASUC). We evaluated serial thrombotic profiles of patients with ASUC from the point of hospitalization up to 12 weeks post-discharge and compared these with control patients with quiescent UC.

Methods: Twenty-seven patients with ASUC and 25 control patients with quiescent ulcerative colitis (UC) were recruited.

A novel three-dimensional model of Infantile Haemangioma.

Infantile Haemangioma (IH) is vascular tumour in infants exhibiting rapid proliferation and angiogenesis followed by gradual involution.10% of cases are associated with disfiguring complications and requires medical interventions with β-blockers such as propranolol, surgery, or laser therapy. An in vitro IH three-dimensional (3D) model will improve our understanding of the disease mechanism(s).

Immune stress and diet influence reproductive fitness in male tuatara ().

The theoretical trade-off between immune and endocrine investment in mating animals has received mixed empirical support, particularly in reptiles. We investigated the relationship between male sexual characteristics, diet, and immune response to stress in an island population of tuatara () across two mating seasons. Tuatara are promiscuous, with a highly skewed mating system where males face significant competition for access to mates and postcopulatory competition for fertilization success.

Decline of antibodies to major viral and bacterial respiratory pathogens during the COVID-19 pandemic.

Surges in infections caused by respiratory pathogens have been documented in multiple settings after relaxation of pandemic restrictions. Antibodies to major antigens from respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal adult cohort throughout the pandemic. This waning may have contributed to the pathogen-surges that followed.

Process of development of decentralised clinical trial methodology for cancer clinical trials in Aotearoa New Zealand.

Aim: To develop processes for the development of decentralised clinical trial methodology for Aotearoa New Zealand, focussing on equity of access to cancer clinical trials for Māori, Pacific people, vulnerable communities and those in rural settings.

Methods: A national steering committee supported by Te Aho o Te Kahu - Cancer Control Agency was formed to: guide the adaptation and implementation of overseas decentralised clinical trial models to suit the needs of Aotearoa New Zealand with an equity focus; provide high-level oversight and expertise for direction and development of policies, procedures and infrastructure compliant with ICH GCP R2; and implement a national strategy.

Results: Twelve standard operating procedures were developed, as well as a supervision plan and a glossary.

An In Vitro-In Vivo Comparative Study Using Highly Sensitive Radioisotopic Assays to Assess the Predictive Power of Emerging Blood-Brain Barrier Models.

Microfluidic BBB-on-a-chip models (μBBB) aim to recapitulate the organotypic features of the human BBB with great potential to model CNS diseases and advance CNS therapeutics. Nevertheless, their predictive capacity for drug uptake into the brain remains uncertain due to limited evaluation with only a small number of model drugs. Here, the in vivo brain uptake of a panel of nine radiolabeled compounds is evaluated in Swiss-outbred mice following a single intravenously administered dose and compared against results from the microfluidic μBBB platform and the conventional Transwell BBB model.

Use of Freestyle Libre 2.0 in children with type 1 diabetes mellitus and elevated HbA: Extension phase results after a 12-week randomized controlled trial.

Aim: To investigate extension phase outcomes with intermittently scanned continuous glucose monitoring (isCGM 2.0) in children with type 1 diabetes mellitus (T1DM) and elevated HbA (7.5-12.

The Impact of Clinical Features on Survival and Relapse of Patients Diagnosed With T-cell Acute Lymphoblastic Leukemia - a Multicenter Cohort Study.

Background: T-cell acute lymphoblastic leukemia (T-ALL) remains understudied compared to B-cell ALL, especially in Latin America. Different biology and response to chemotherapy have been described.

Methods: This retrospective multi-site cohort study analyzed data from 152 newly diagnosed T-ALL patients aged 15 years and above, between January 2010 and June 2022.

Characteristics and outcomes of adults with acute brain injuries admitted to intensive care units in Australia and New Zealand from 2013 to 2022.

Background: The characteristics and outcomes of patients with acute brain injuries admitted to the intensive care unit (ICU) in Australia and New Zealand (ANZ) are insufficiently described.

Objective: This study aimed to describe the epidemiology of acute brain injury in ICU patients in ANZ.

Methods: A binational retrospective cohort study was conducted using the ANZ Intensive Care Society Adult Patient Database.

The use of prescription medication and other drugs by New Zealand drivers with illegal blood alcohol levels.

Objective: This study examined the prevalence of the use of prescription medicines and other drugs by a selected subgroup of New Zealand drivers. The use of potentially impairing prescription drugs by the driving population is largely unknown. The population studied was drivers who were stopped by police, failed a breath alcohol test, elected to provide a blood sample for laboratory analysis, and had blood alcohol levels exceeding the legal limit.

A Small Intestinal Helminth Infection Alters Colonic Mucus and Shapes the Colonic Mucus Microbiome.

Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. In this study, we compare C57BL/6 mice infected with the small intestinal helminth and uninfected controls to investigate changes in colonic mucus.

Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections.

Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days.

Exploiting blood-based biomarkers to align preclinical models with human traumatic brain injury.

Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%. While there are several potential explanations for this, previous clinical trials have relied on extrapolation from preclinical studies for critical design considerations, including drug dose optimization, post-injury drug treatment initiation and duration.

Equity of access to pathological diagnosis and bronchoscopy for lung cancer in Aotearoa New Zealand.

Background: Māori are less likely to survive their lung cancer once diagnosed, but it remains unclear whether this is partially driven by poorer access to best-practice diagnostic services.

Methods: We examined all lung cancer registrations in Aotearoa New Zealand between 2007-2019 (n=27,869) linked to national administrative health datasets and further stratified by ethnicity, tumour type and stage of disease. Using descriptive and regression analyses, we compared ethnic groups in terms of the basis of diagnosis (e.

The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.

ASPRONET: A facilitated online education project for radiation therapists in the Asia-Pacific region.

In 2019, the International Atomic Energy Agency approved a technical co-operation project, aimed at supporting clinical decision making and continuing professional education of radiation oncologists, medical physicists and radiation therapists (RTs) in Low-and-Middle Income Countries (LMICs) in the Asia Pacific region. From this, the Asia-Pacific Radiation Oncology Network (ASPRONET) was formed in 2020. An RT co-ordination group administered 16 online, one-hour seminars between December 2021 and November 2023 for an RT audience.