Toxic eburicol accumulation drives the antifungal activity of azoles against Aspergillus fumigatus.

Azole antifungals inhibit the sterol C14-demethylase (CYP51/Erg11) of the ergosterol biosynthesis pathway. Here we show that the azole-induced synthesis of fungicidal cell wall carbohydrate patches in the pathogenic mold Aspergillus fumigatus strictly correlates with the accumulation of the CYP51 substrate eburicol. A lack of other essential ergosterol biosynthesis enzymes, such as sterol C24-methyltransferase (Erg6A), squalene synthase (Erg9) or squalene epoxidase (Erg1) does not trigger comparable cell wall alterations.

Wearable sensor and smartphone assisted vestibular physical therapy for multiple sclerosis: usability and outcomes.

Introduction: Vertigo, dizziness, gaze instability and disequilibrium are highly prevalent in people with MS (PwMS) and head movement induced dizziness is commonly reported. Vestibular physical therapy (VPT) is a specialised, non-invasive and effective therapy for these problems but usually involves travel for the person to a specialist center with both personal and carbon costs. The use of wearable sensors to track head movement and smartphone applications to deliver and track programs has potential to improve VPT in MS.

Blood Micro-sampling: An alternative blood collection method for radioiodine therapy dosimetry.

Purpose: Collecting venous blood samples from patients post administration of high therapeutic activities results in radiation exposure to staff collecting the blood. This study investigated the use of finger-tip capillary-blood collection as an alternative to the venous-blood collection method recommended by the European Association of Nuclear Medicine (EANM) dosimetry protocol for quantifying I concentration in the critical organ after therapeutic dose of I.

Methods: The study included differentiated thyroid cancer patients referred to a thyroid cancer centre at St James's Hospital, Ireland, for therapeutic and diagnostic oral administration of I.

The Impact of the Fungal Priority Pathogens List on Medical Mycology: A Northern European Perspective.

Fungal diseases represent a considerable global health concern, affecting >1 billion people annually. In response to this growing challenge, the World Health Organization introduced the pivotal fungal priority pathogens list (FPPL) in late 2022. The FPPL highlights the challenges in estimating the global burden of fungal diseases and antifungal resistance (AFR), as well as limited surveillance capabilities and lack of routine AFR testing.

Blood Cancer Network Ireland (BCNI) and National Cancer Registry Ireland (NCRI) collaboration: challenges and utility of an Enhanced Blood Cancer Outcomes Registry (EBCOR) pilot.

Background: The Blood Cancer Network Ireland and National Cancer Registry Ireland worked to create an Enhanced Blood Cancer Outcomes Registry (EBCOR). Enhanced data in acute myeloid leukaemia (AML) included an extensive data dictionary, bespoke software and longitudinal follow-up.

Aims: To demonstrate the utility of the database, we applied the data to examine a clinically relevant question: Charlson comorbidity index (CCI) usefulness in predicting AML patients' survival.

Prioritising Key Concepts for informed health choices in cancer: An evidence-based online educational programme.

Objective: The overabundance of health misinformation has undermined people's capacity to make evidence-based, informed choices about their health. Using the Informed Health Choices (IHC) Key Concepts (KCs), we are developing a two-stage education programme, Informed Health Choices-Cancer (IHC-C), to provide those impacted by cancer with the knowledge and skills necessary to think critically about the reliability of health information and claims and make well-informed choices. Stage 1 seeks to prioritise the most relevant Key Concepts.

Computed tomography (CT) derived radiomics to predict post-operative disease recurrence in gastric cancer; a systematic review and meta-analysis.

Introduction: Radiomics offers the potential to predict oncological outcomes from pre-operative imaging in order to identify 'high risk' patients at increased risk of recurrence. The application of radiomics in predicting disease recurrence provides tailoring of therapeutic strategies. We aim to comprehensively assess the existing literature regarding the current role of radiomics as a predictor of disease recurrence in gastric cancer.

von Willebrand factor antigen, von Willebrand factor propeptide and ADAMTS13 activity in TIA or ischaemic stroke patients changing antiplatelet therapy.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays).

Reducing recurrence rates in hiatal hernia repair: Results of a quality improvement study.

Background: Patient and procedure factors are considered in the decision-making process for surgical repair of hiatal hernias. Recurrence is multi-factorial and has been shown to be related to size, type, BMI and age.

Aims: This study examined recurrence rates in a single institution, identified areas for improved surgical technique, and re-assessed recurrence following implantation of a quality improvement initiative.

Exploring the readiness of the Irish healthcare system to adopt advanced therapies: a scoping review protocol.

Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer groundbreaking new opportunities for the treatment of disease and injury. However, ATMP adoption requires adjustments to current clinical practices and frameworks.

Inequalities in access to neuro-oncology supportive care and rehabilitation: A survey of healthcare professionals' perspectives.

Background: Neuro-oncology patients and caregivers should have equitable access to rehabilitation, supportive-, and palliative care. To investigate existing issues and potential solutions, we surveyed neuro-oncology professionals to explore current barriers and facilitators to screening patients' needs and referral to services.

Methods: Members of the European Association of Neuro-Oncology and the European Organisation for Research and Treatment of Cancer Brain Tumor Group (EORTC-BTG) were invited to complete a 39-item online questionnaire covering the availability of services, screening, and referral practice.

ROS1 fusions in resected stage I-III adenocarcinoma: Results from the European Thoracic Oncology Platform Lungscape project.

Background: ROS1 fusion is a relatively low prevalence (0.6-2.0%) but targetable driver in lung adenocarcinoma (LUAD).

International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning.

Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients.

R1205H (Vicenza) causes conformational changes in the von Willebrand factor D'D3 domains and enhances von Willebrand factor binding to clearance receptors LRP1 and SR-AI.

Background: von Willebrand factor (VWF)-R1205H variant (Vicenza) results in markedly enhanced VWF clearance in humans that has been shown to be largely macrophage-mediated. However, the biological mechanisms underlying this enhanced clearance remain poorly understood.

Objectives: This study aimed to investigate the roles of (i) specific VWF domains and (ii) different macrophage receptors in regulating enhanced VWF-R1205H clearance.

A clinical practice guideline for primary care physiotherapy in patients with haemophilia.

Introduction: As a result of centralisation of haemophilia care to a limited number of intramural settings, many persons with haemophilia have to travel long distances to attend their haemophilia specialised treatment centre. However, regular physiotherapy treatment can be provided by primary care physiotherapists in the person's own region. Due to the rarity of the disease most primary care physiotherapists have limited experience with this population.

Moving towards Normalization of haemostasis and health equity: Evolving treatment goals for haemophilia A.

Background: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile.

Treatment Goals: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care.

Airway decision making in major head and neck surgery: Irish multicenter, multidisciplinary recommendations.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units.

Impact of preoperative intra-aortic balloon pump on outcomes in coronary artery bypass grafting for unprotected left-main coronary artery disease.

Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes.

Impact of COVID-19 vaccination on seminal and systemic inflammation in men.

Expedited development of SARS-CoV-2 vaccines led to public concerns regarding impacts of the novel vaccine on gametes in patients seeking assisted reproduction. In cases of an acute intermittent illness or fever in men, it is often advised to postpone ART treatments so that efforts can be made to enhance wellbeing and improve sperm parameters. However, it is unknown whether sperm parameters are altered in the acute (24-72 hour) phase following COVID-19 vaccination.