Mass spectrometry imaging protocol for spatial mapping of lipids, N-glycans and peptides in murine lung tissue.

Rationale: The application of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to murine lungs is challenging due to the spongy nature of the tissue. Lungs consist of interconnected air sacs (alveoli) lined by a single layer of flattened epithelial cells, which requires inflation to maintain its natural structure. Therefore, a protocol that is compatible with both lung instillation and high spatial resolution is essential to enable multi-omic studies on murine lung disease models using MALDI-MSI.

CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL.

CD19-negative relapse is a leading cause of treatment failure after chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral cotransduction with vectors encoding our previously described fast-off rate CD19 CAR (AUTO1) combined with a novel CD22 CAR capable of effective signaling at low antigen density. Twelve patients with advanced B-cell acute lymphoblastic leukemia were treated (CARPALL [Immunotherapy with CD19/22 CAR Redirected T Cells for High Risk/Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia] study, NCT02443831), a third of whom had failed prior licensed CAR therapy.

Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants.

The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics - such as varying levels of immunity - can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends.

Performance comparison of homologous and heterologous Newcastle disease virus in vaccines and antibody tests.

Antigenic differences between commercial Newcastle Disease Virus (NDV) vaccine and circulating field virus reduce vaccine efficacy. Fifty-layer chickens were divided into five groups: three vaccinated chicken groups using killed LaSota (Genotype II/GII), Mega, or VD (Genotype VII/GVII) viral strains, negative, and positive control groups. On day 28, Hemagglutination Inhibition (HI) serology of vaccinated chickens was performed using whole virus antigens of RIVS, LaSota, Mega, and VD strains.

Evaluation of Nomacopan for Treatment of Bullous Pemphigoid: A Phase 2a Nonrandomized Controlled Trial.

Importance: Bullous pemphigoid is a difficult-to-treat autoimmune blistering skin disease that predominantly affects older adults and is associated with an increased mortality rate.

Objective: To examine the safety and therapeutic potential of nomacopan, an inhibitor of leukotriene B4 and complement C5, in patients with bullous pemphigoid.

Design, Setting, And Participants: This multicenter, single-group, phase 2a nonrandomized controlled trial was conducted in the dermatology departments of universities in the Netherlands and Germany.

The rs9939609 Variant Is Associated with Cardiometabolic Disease Risk and Dietary Energy Intakes in Children with Mental Health Disorders.

Background: Second-generation antipsychotics (SGAs) are used to treat children for mental health disorders but in some children they cause cardiometabolic complications including weight gain and type 2 diabetes. Genetic variants can place a child at risk of developing these metabolic complications. The fat mass and obesity-associated () rs9939609 A allele has been associated with obesity and dietary energy intakes in healthy children but its relation to metabolic complications in SGA-treated children is not known.

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial.

Purpose: Ganetespib, a highly potent, small-molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the maximum tolerated dose (MTD) of ganetespib in patients with chemotherapy-naïve MPM.

Patients And Methods: MESO-02 (ClinicalTrials.

Long-Term Results from the IDEAL-CRT Phase 1/2 Trial of Isotoxically Dose-Escalated Radiation Therapy and Concurrent Chemotherapy for Stage II/III Non-small Cell Lung Cancer.

Purpose: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule.

Methods And Materials: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine.

New Service Model for Common Mental Disorders in Hong Kong: a Retrospective Outcome Study.

Objective: To review the first 8-month outcome of the Common Mental Disorder Clinic model in Hong Kong in terms of patient exit status and improvement in depressive and anxiety symptoms.

Methods: During the first appointment, patients were interviewed by a multidisciplinary team comprising a psychiatrist, a psychiatric nurse, and an occupational therapist. A multidisciplinary case conference was conducted to discuss clinical observations, diagnosis, issues of concern, and the optimal individualised treatment plan.

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

Background: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy.

Methods: LungSEARCH was a national multicentre randomised trial.

The clinical role of VeriStrat testing in patients with advanced non-small cell lung cancer considered unfit for first-line platinum-based chemotherapy.

Purpose: We previously demonstrated that the median survival of patients with poor prognosis non-small cell lung cancer (NSCLC) considered unfit for first-line platinum chemotherapy was <4 months. We evaluated whether VeriStrat could be used as a prognostic or predictive biomarker in this population.

Experimental Design: We conducted a randomised double-blind trial among patients with untreated advanced NSCLC considered unfit for platinum chemotherapy because of poor performance status (PS) or multiple comorbidities.

Optimal liver stiffness measurement values for the diagnosis of significant fibrosis and cirrhosis in chronic liver disease in Singapore.

Introduction: Despite the widespread use of transient elastography for non-invasive assessment of liver fibrosis, the optimal cut-off liver stiffness measurement (LSM) values remain unclear. This study aimed to validate the optimal cut-off LSM values for significant fibrosis and cirrhosis in patients with chronic liver disease (CLD).

Methods: Prospective multicentre data of CLD patients who underwent paired liver biopsy and LSM was analysed to determine the optimal cut-off LSM values for predicting significant fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4).

Risperidone But Not Quetiapine Treatment Is Associated With Increased Appetite But Not Satiety Hormones in Children During An Oral Glucose Tolerance Test: A Pilot Study.

Background: Second-generation antipsychotics (SGAs) are commonly used to treat children with mental health conditions (MHCs) but are associated with adverse effects including obesity, hypertension, dyslipidemia, and type 2 diabetes. The mechanisms underlying these complications are unknown, but it has been suggested that SGAs increase appetite leading to weight gain. The present objective was to perform a pilot study to investigate appetite and satiety hormones in SGA-treated (risperidone or quetiapine) and SGA-naive children with similar mental health conditions.

Novel CT-Based Objective Imaging Biomarkers of Long-Term Radiation-Induced Lung Damage.

Purpose: Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long-term radiation-induced lung damage (RILD). However, there are still no objective criteria to quantify RILD, leading to variable reporting across centers and trials. We propose a set of objective imaging biomarkers for quantifying common radiologic findings observed 12 months after lung cancer radiation therapy.

Study protocol for the SARON trial: a multicentre, randomised controlled phase III trial comparing the addition of stereotactic ablative radiotherapy and radical radiotherapy with standard chemotherapy alone for oligometastatic non-small cell lung cancer.

Introduction: Following growing evidence to support the safety, local control (LC) and potential improvement in overall survival (OS) in patients with oligometastatic non-small cell lung cancer (NSCLC) that have been treated with local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS), we initiate the SARON trial to investigate the impact and feasibility of adding SABR/SRS and radical radiotherapy (RRT) following standard chemotherapy on OS.

Methods And Analysis: SARON is a large, randomised controlled, multicentre, phase III trial for patients with oligometastatic EGFR, ALK and ROS1 mutation negative NSCLC (1-3 sites of synchronous metastatic disease, one of which must be extracranial). 340 patients will be recruited over 3 years from approximately 30 UK sites and randomised to receive either standard platinum-doublet chemotherapy only (control arm) or standard chemotherapy followed by RRT/SABR to their primary tumour and then SABR/SRS to all other metastatic sites (investigational arm).

Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

This corrects the article DOI: 10.1038/nature22364.

The Impact of Cardiac Radiation Dosimetry on Survival After Radiation Therapy for Non-Small Cell Lung Cancer.

Purpose: The heart receives high radiation doses during radiation therapy of advanced-stage lung cancer. We have explored associations between overall survival, cardiac radiation doses, and electrocardiographic (ECG) changes in patients treated in IDEAL-CRT, a trial of isotoxically escalated concurrent chemoradiation delivering tumor doses of 63 to 73 Gy.

Methods And Materials: Dosimetric and survival data were analyzed for 78 patients.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study.

Tracking the Evolution of Non-Small-Cell Lung Cancer.

Background: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.

Methods: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy.