Visualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta.

Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution. See related article by Bressan et al.

3D-printed drill guide versus fluoroscopic-guided free-hand technique for pedicle screw insertion in the upper cervical spine: a systematic review and meta-analysis.

3D-printed (3DP) drill guides have demonstrated significant potential to accurately guide pedicle screw insertion in spinal surgery. However, their role in the upper cervical spine is not well established. This review aimed to compare the efficacy and safety of 3DP drill guides to the conventional fluoroscopic-guided free-hand technique for pedicle screw insertion in the upper cervical spine.

Integration of a specialist pharmacist-led multidisciplinary team in primary care: preventing strokes in people with atrial fibrillation across North East London.

Public Health England outlines a national ambition of anticoagulating 90% of eligible patients with atrial fibrillation (AF) by 2029. In 2019/2020, two out of three boroughs reviewed in this study were in the bottom 10% of boroughs compared with others within England. Stroke National Audit data for these three boroughs from 2019 to 2020 identified that in patients with known AF admitted to hospital with strokes, 37% were not anticoagulated.

Depression and dementia: interrogating the causality of the relationship.

Background: Depression is often cited as a major modifiable risk factor for dementia, though the relative contributions of a true causal relationship, reverse causality and confounding factors remain unclear. This study applied a subset of the Bradford Hill criteria for causation to depression and dementia including strength of effect, specificity, temporality, biological gradient and coherence.

Methods: A total of 491 557 participants in UK Biobank aged between 40 and 69 at enrolment and followed up for a mean duration of 12.

Prevalence of Chronic Hand Eczema in adults: A cross-sectional survey of over 60,000 respondents in the general population in Canada, France, Germany, Italy, Spain, and the United Kingdom.

Background: The lack of attention to Chronic Hand Eczema (CHE) and the lack of a specific International Classification of Diseases code for CHE may have limited the assessment of CHE prevalence. To date, prevalence estimates have primarily been derived from (partly small) single-country studies.

Objectives: To estimate the annual prevalence of self-reported physician-diagnosed CHE across socio-demographic characteristics among adults in Canada, France, Germany, Italy, Spain, and the United Kingdom (UK).

Subclavian Ansae Stimulation on Cardiac Hemodynamics and Electrophysiology in Atrial Fibrillation: A Target for Sympathetic Neuromodulation.

Background: The sympathetic autonomic nervous system plays a major role in arrhythmia development and maintenance. Historical preclinical studies describe preferential increases in cardiac sympathetic tone upon selective stimulation of the subclavian ansae (SA), a nerve cord encircling the subclavian artery.

Objectives: This study sought to define, for the first time, the functional anatomy and physiology of the SA in humans using a percutaneous approach.

Exploring the Link Between Obligate Anaerobe-Related Dysbiosis and Prostate Cancer Development: A Pilot Study.

Background/objectives: Several independent studies have associated prostate cancer (PCa) with specific groups of bacteria, most of them reporting the presence of anaerobic or microaerophilic species such as (). Such findings suggest a prostate cancer-related bacterial dysbiosis, in a manner similar to the association between infection and gastric cancer. In an earlier exploratory study looking for such dysbiosis events, using a culturomics approach, we discovered that the presence of obligate anaerobes (OAs) along with was associated with increased prostate-specific antigen (PSA) levels in 39 participants.

Use of a Non-Endoscopic Capsule-Sponge Triage Test for Reflux Symptoms: Results From the NHS England Prospective Real-World Evaluation.

Background: Acid reflux is a common presentation in primary care leading to a high volume of referrals to endoscopy that are often normal.

Aims: To determine whether a non-endoscopic capsule sponge biomarker test could triage patients with low-risk reflux symptoms, reduce endoscopy waiting lists and identify Barrett's oesophagus in a real-world setting.

Methods: Patients with reflux symptoms on NHS endoscopy waiting lists who were offered a capsule sponge (test group) between February 2021 and August 2022 were included in this national multicentre prospective cohort study and compared with eligible patients on the standard endoscopy pathway (counterfactual group).

Augmentation with the inferior extensor retinaculum may facilitate earlier recovery in all-inside arthroscopic management of chronic lateral ankle instability.

Background: To compare the clinical outcomes of inferior extensor retinaculum (IER) augmentation following repair of the anterior talofibular ligament (ATFL) with isolated ATFL repair in patients with an arthroscopically confirmed grade 3 lesion of the ATFL.

Methods: We conducted a retrospective study of consecutive chronic lateral ankle instability (CLAI) patients who underwent arthroscopic ATFL repair between March 2018 and August 2022. The average age of the patients was 31.

Transient apical breakdown associated with clear aligner therapy: a case report.

Transient apical breakdown (TAB) is widely reported in response to trauma, yet its occurrence due to orthodontic forces, particularly in aligner therapy, is less documented within current literature. TAB can easily be misdiagnosed as pulp necrosis, potentially leading to unnecessary and irreversible endodontic procedures. This case report describes an instance of TAB following the initiation of aligner treatment, where the affected tooth initially presented with signs suggesting pulp necrosis but regained normal coloration and pulpal response after six months of active monitoring.

SNOMED-CT and learning health systems for NHS dentistry - a dream needing to become reality.

There has been discussion and confusion about SNOMED-CT (systematised nomenclature of medicine clinical terminology), learning health systems (LHSs) and their relevance in dentistry. This article aims to provide an overview of SNOMED-CT, LHSs and the all-too-often omitted patient and service benefits from their use. LHSs are delivering impactful benefits to patients and services globally in medicine.

Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.

Beyond dyslipidemia, inflammation contributes to the development of atherosclerosis. However, intrinsic factors that counteract vascular inflammation and atherosclerosis remain scarce. Here we identify insulin-like growth factor binding protein 6 (IGFBP6) as a homeostasis-associated molecule that restrains endothelial inflammation and atherosclerosis.

Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats.

The COVID-19 pandemic exposed a global deficiency of systematic, data-driven guidance to identify high-risk individuals. Here, we illustrate the utility of routinely recorded medical history to predict the risk for 1741 diseases across clinical specialties and support the rapid response to emerging health threats such as COVID-19. We developed a neural network to learn from health records of 502,489 UK Biobank participants.

Retinal Sensitivity in KCNV2-Associated Retinopathy.

Purpose: The purpose of this study was to analyze the retinal sensitivity under photopic, mesopic, and scotopic conditions in a cohort of patients affected with KCNV2-associated retinopathy.

Methods: Cross-sectional evaluation of molecularly confirmed individuals was conducted. Data were obtained prospectively.

Formulas to estimate dietary sodium intake from spot urine lead to misleading associations with cardiovascular disease risk and mortality.

Objectives: To test the hypothesis that the association of formula-estimated sodium intake from spot urine with cardiovascular disease is independent of spot urinary sodium concentration.

Methods: We included 435 336 participants in the UK Biobank whose sodium intake was estimated from spot urine using INTERSALT, Kawasaki, and Tanaka formulas. Hazard ratios for cardiovascular disease (CVD) events and deaths were estimated using Cox proportional-hazard model adjusted for multiple covariates.

Causes of death in patients with atrial fibrillation in the UK: a nationwide electronic health record study.

Aims: Causes of death remain largely unexplored in the atrial fibrillation (AF) population. We aimed to (i) thoroughly assess causes of death in patients with AF, especially those associated with sudden cardiac death (SCD) and (ii) evaluate the potential association between AF and SCD.

Methods And Results: Linked primary and secondary care United Kingdom Clinical Practice Research Datalink dataset comprising 6 529 382 individuals aged ≥18.

Computational pathology applied to clinical colorectal cancer cohorts identifies immune and endothelial cell spatial patterns predictive of outcome.

Colorectal cancer (CRC) is a histologically heterogeneous disease with variable clinical outcome. The role the tumour microenvironment (TME) plays in determining tumour progression is complex and not fully understood. To improve our understanding, it is critical that the TME is studied systematically within clinically annotated patient cohorts with long-term follow-up.

Spatial transcriptomic analysis reveals significant differences in tumor microenvironment in HPV-dependent and HPV-independent vulvar squamous cell carcinoma.

Objective: Vulvar squamous cell carcinoma (VSCC) can be either HPV-dependent (HPVd) or HPV-independent (HPVi). HPVd VSCC typically occurs in younger women, has a more favorable prognosis, and develops from high-grade squamous intraepithelial lesions (HSIL). HPVi VSCC predominantly affects older women and arises within areas of chronic inflammation, particularly lichen sclerosis (LS).

Lymphatic leaks - success of intranodal lymphangiogram first strategy.

Background: Lymphatic leaks are associated with significant mortality and morbidity. Intranodal lymphangiography (ILAG) involves the direct injection of ethiodised lipid into the hilum of lymph nodes. It is diagnostic procedure that can have therapeutic effects secondary to a local sclerosant effect.