Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.

Background: Millions worldwide are exposed to elevated levels of arsenic that significantly increase their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations.

Objectives: This study aimed to conduct single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout () mice to elucidate transcriptomic and epigenetic changes in immune cells induced by arsenic exposure.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Factors associated with mortality in thoracic trauma patients in Cameroon.

Background: Thoracic trauma is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. The identification of a patient at risk of thoracic trauma mortality is necessary to avoid delays that may lead to morbidity and mortality. Therefore, the objective was to assess the factors associated with mortality among thoracic trauma patients in Cameroon.

Wealth is health: High economic status in Cameroon correlates with protective gear use in traffic injuries and improved clinical outcomes.

Introduction: Africa is the least motorized populated continent, yet it experiences the highest traffic fatality rate. Despite laws mandating helmet and seatbelt use, data on protective gear use among Cameroonian road traffic injury (RTI) patients remains sparse.

Methods: We extracted Cameroon Trauma Registry data prospectively collected from 10 hospitals during July 2022 to December 2023.

IPEM code of practice for proton therapy dosimetry based on the NPL primary standard proton calorimeter calibration service.

Internationally, reference dosimetry for clinical proton beams largely follows the guidelines published by the International Atomic Energy Agency (IAEA TRS-398 Rev. 1, 2024). This approach yields a relative standard uncertainty of 1.

The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study.

Purpose: The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers.

Methods: Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient).

Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

Best Practice for Patient-centred Radiotherapy in Clinical Trials and Beyond-A National Multidisciplinary Consensus.

Aims: Patient-centred radiotherapy refers to an approach where patients' needs and preferences are prioritised. Guidelines for this personalised approach are lacking. We present a multidisciplinary national consensus with the aim to provide recommendations for best practice in patient-centred radiotherapy for both clinical trials and routine practice.

Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.

Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

Decrease in Fracture Rate with Mandatory Bone-protecting Agents in the EORTC 1333/PEACE-3 Trial Comparing Radium-223 Combined with Enzalutamide Versus Enzalutamide Alone: A Safety Analysis.

Bone health is central to the management of patients with metastatic castration-resistant prostate cancer (mCRPC). International guidelines recommend giving a bone-protecting agent (BPA) to patients with mCRPC and bone metastases. However, the data supporting these recommendations were generated before androgen receptor pathway inhibitors (ARPIs) were available.

Targeted therapy for older patients with an oncogene driven non-small cell lung cancer: Recommendations from a SIOG expert group.

Lung cancer is mostly a disease of aging with approximately half of newly diagnosed patients being 70 years or older. Treatment decisions in this population pose unique challenges because of their heterogeneity with regards to daily functioning, cognition, organ function, comorbidities and polypharmacy, their underrepresentation in clinical trials and the impact of treatment on patient-centered outcomes, particularly in frail patients. The advent of targeted therapies and immunotherapy has revolutionized the management of advanced non-small cell lung cancer (NSCLC).

Multidimensional fatigue and its impact on work productivity, mood and quality of life in long-term survivors following definitive intensity-modulated radiotherapy for oropharyngeal cancer: A cross-sectional study.

Purpose: Radiotherapy (RT) for oropharyngeal cancer (OPC) can lead to late toxicity. Fatigue is a known debilitating issue for many cancer survivors, yet prevalence and severity of long-term fatigue in patients treated for OPC is unknown.

Method: As part of a mixed-methods study, fatigue in OPC patients ≥ 2 years post RT + / - chemotherapy was evaluated.

Low-risk febrile neutropenia: does combined chemotherapy/immune checkpoint inhibitor necessitate a change in approach?

Purpose: Management of patients with low-risk febrile neutropenia in an outpatient setting guided by the MASCC score is proven to be safe and effective. Most patients on ambulatory low-risk febrile neutropenia pathways are undergoing treatment for breast cancer. Recent data has shown benefit of the addition of immune checkpoint inhibitor therapy to cytotoxic chemotherapy in the neoadjuvant setting for patients with early triple-negative breast cancer.

Loss of correlated proteasomal subunit expression selectively promotes the 20S state which underlies luminal breast tumorigenicity.

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.

A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab, as first-line treatment for advanced pleural mesothelioma: results of the ETOP 13 18 BEAT-meso trial.

Background: The currently approved frontline treatments for diffuse pleural mesothelioma (DPM) are ipilimumab-nivolumab or platinum-pemetrexed. The addition of bevacizumab to chemotherapy improves overall survival (OS). While single-agent immunotherapy or chemotherapy-immunotherapy combinations are superior to chemotherapy monotherapy, there is a potential for synergistic triple combination of chemotherapy, bevacizumab, and immunotherapy.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Variations in linear energy transfer distributions within a European proton therapy planning comparison of paediatric posterior fossa tumours.

Background And Purpose: Radiotherapy for paediatric posterior fossa tumours may cause complications in the brainstem and upper spinal cord due to high doses. With proton therapy (PT) this risk may increase due to higher relative biological effectiveness (RBE) from elevated linear energy transfer (LET). This study assesses variations in LET in the brainstem and spinal cord in proton treatment plans from European centres.

First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study.

Introduction: SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.

Translation of dynamic contrast-enhanced imaging onto a magnetic resonance-guided linear accelerator in patients with head and neck cancer.

Background And Purpose: Magnetic resonance imaging - linear accelerator (MRI-linac) systems permit imaging of tumours to guide treatment. Dynamic contrast enhanced (DCE)-MRI allows investigation of tumour perfusion. We assessed the feasibility of performing DCE-MRI on a 1.

Radiotherapy Quality Assurance in the SCOPE2 Trial: What Lessons can be Learned for the Next UK Trial in Oesophageal Cancer?

Aims: The SCOPE2 trial evaluates radiotherapy (RT) dose escalation for oesophageal cancer. We report findings from the accompanying RT quality assurance (RTQA) programme and identify recommendations for PROTIEUS, the next UK trial in oesophageal RT.

Maetrials And Methods: SCOPE2's RTQA programme consisted of a pre-accrual and on-trial component.

Life after Pelvic Exenteration for Rectal Cancer: The Patient and Carer Perspective on Long Term Consequences and Survivorship.

Objective: To explore the perspectives and experiences of patients and carers living with the long-term consequences of pelvic exenteration.

Summary Background Data: Pelvic exenteration is accepted as the standard of care for selected patients with locally advanced or recurrent rectal cancer. With contemporary 5-year survival reported at 40-60%, the number of long-term survivors is expected to increase.