Image-Guided Ablation of Renal Masses: Challenges to Produce High-Quality Evidence and Future Directions.

Image-guided ablation (IGA) is a rapidly developing field in interventional oncology. There is some evidence suggesting IGA's non-inferiority compared with partial or radical nephrectomy for the treatment of small renal masses (SRM). However, these are mostly limited to retrospective cohort studies.

Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip.

Organs-on-chips (OoCs) support an organotypic human cell culture . Precise representation of basement membranes (BMs) is critical for mimicking physiological functions of tissue interfaces. Artificial membranes in polyester (PES) and polycarbonate (PC) commonly used in models and OoCs do not replicate the characteristics of the natural BMs, such as submicrometric thickness, selective permeability, and elasticity.

Quality standards for the management of alcohol-related liver disease: consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology ARLD special interest group.

Objective: Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care.

Affimer-mediated locking of p21-activated kinase 5 in an intermediate activation state results in kinase inhibition.

Kinases are important therapeutic targets, and their inhibitors are classified according to their mechanism of action, which range from blocking ATP binding to covalent inhibition. Here, a mechanism of inhibition is highlighted by capturing p21-activated kinase 5 (PAK5) in an intermediate state of activation using an Affimer reagent that binds in the P+1 pocket. PAK5 was identified from a non-hypothesis-driven high-content imaging RNAi screen in urothelial cancer cells.

Diabetes is associated with increased burden of gastrointestinal symptoms in adults with cystic fibrosis.

Background: Individuals with diabetes mellitus (DM) are known to frequently experience gastrointestinal (GI) symptoms. In contrast, the impact of cystic fibrosis-related diabetes (CFRD) on accentuating GI symptoms in people with cystic fibrosis (pwCF) is unknown. We sought to examine this.

Prevalence of medically unexplained symptoms in adults who are high users of healthcare services and magnitude of associated costs: a systematic review.

Introduction: Medically unexplained symptoms (MUS) is a common clinical syndrome in primary and secondary healthcare service. Outcomes for patients with persistent MUS include increased disability, poorer quality of life and higher healthcare costs. The aim of this systematic review was to determine the prevalence of MUS in patients who are high users of healthcare or high-cost patients in comparison with routine users and the magnitude of associated costs.

Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses.

Objectives: To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs).

Methods: This prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen.

Conditional Knockout Mouse Models to Study the Roles of Individual NF-κB Transcription Factors in Lymphocytes.

The NF-κB signal transduction pathway has crucial functions in cell growth, survival, and the development of lymphocytes and other immune cells. Upon activation of the pathway, five distinct NF-κB transcription factor subunits that occur as homodimers or heterodimers comprise the downstream mediators that transcribe NF-κB target genes. A major quest in NF-κB research is to understand the biology of the separate subunits.

The DANTE trial protocol: a randomised phase III trial to evaluate the Duration of ANti-PD-1 monoclonal antibody Treatment in patients with metastatic mElanoma.

Background: Immunotherapy is revolutionising the treatment of patients diagnosed with melanoma and other cancers. The first immune checkpoint inhibitor, ipilimumab (targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)), showed a survival advantage over standard chemotherapy. Subsequently the anti-programmed cell death protein 1 (PD-1) antibodies, nivolumab and pembrolizumab were shown to be more effective than ipilimumab.

Neurodegenerative Disease and the NLRP3 Inflammasome.

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by a progressive neuronal loss in the brain or peripheral nervous system, and generally involve protein aggregation, as well as metabolic abnormalities and immune dysregulation. Although the vast majority of neurodegeneration is idiopathic, there are many known genetic and environmental triggers.

Microbiome Analysis of More Than 2,000 NHS Bowel Cancer Screening Programme Samples Shows the Potential to Improve Screening Accuracy.

Purpose: There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program.

Experimental Design: Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [ = 491 (22%)]; colorectal cancer [ = 430 (19%)]; adenoma [ = 665 (30%)]; colonoscopy-normal [ = 300 (13%)]; nonneoplastic [ = 366 (16%)].

The colorectal cancer-associated faecal microbiome of developing countries resembles that of developed countries.

Background: The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a 'resource-light' sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries.

Methods: We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries.

Early relapse after high-dose melphalan autologous stem cell transplant predicts inferior survival and is associated with high disease burden and genetically high-risk disease in multiple myeloma.

Predicting patient outcome in multiple myeloma remains challenging despite the availability of standard prognostic biomarkers. We investigated outcome for patients relapsing early from intensive therapy on NCRI Myeloma XI. Relapse within 12 months of autologous stem cell transplant was associated with markedly worse median progression-free survival 2 (PFS2) of 18 months and overall survival (OS) of 26 months, compared to median PFS2 of 85 months and OS of 91 months for later relapsing patients despite equal access to and use of subsequent therapies, highlighting the urgent need for improved outcome prediction and early intervention strategies for myeloma patients.

Evaluation of the "Shared Community Follow-up" after a germ cell tumour-A novel initiative for remote cancer follow-up enhanced by online patient-reported outcome measures.

Objective: Replying to germ cell tumour patients' needs, we implemented "Shared Community Follow-up"-a collaborative initiative, enabling remote delivery of specialist cancer care across large geographical areas. Blood, radiological investigations and patient-reported outcome measures (PROMs) are completed remotely and integrated within the electronic patient records for specialist review without patients requiring appointments. We describe the service evaluation estimating the feasibility, safety and acceptability of this initiative versus traditional Standard Follow-up.

Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study.

Despite intensive treatment, 50% of children with high-risk neuroblastoma (HR-NB) succumb to their disease. Progression through current trials evaluating the efficacy of new treatments for children with HR disease usually depends on an inadequate response to induction chemotherapy, assessed using imaging modalities. In this study, we sought to identify circulating biomarkers that might be detected in a simple blood sample to predict patient response to induction chemotherapy.

A T Cell-B Cell Tumor-Suppressive Axis in the Germinal Center.

TNFRSF14, encoding the receptor HVEM, is frequently mutated in germinal center (GC)-derived B cell lymphomas. In this issue, Mintz et al. demonstrate that the HVEM-BTLA axis restrains T cell help to GC B cells.

Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene.

Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.

Discussing factors associated with quality of life in cancer follow-up appointments: a preliminary test of a pragmatic model for clinical practice.

Objective:: The aim of this study is to perform a preliminary test of a practical, evidence-based model to enable discussions around quality of life-related concerns during cancer follow-up appointments.

Design:: Cross-sectional study measuring quality of life, illness perceptions, emotional distress, fatigue, and subjective cognitive complaints.

Setting:: Cancer outpatient follow-up clinics in four National Health Services in the United Kingdom.