50 results match your criteria: "Institute of Genetic and Molecular Medicine[Affiliation]"

Comparative characterization of two monoclonal antibodies targeting canine PD-1.

Front Immunol

May 2024

The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, United Kingdom.

Article Synopsis
  • Monoclonal antibodies that target immune checkpoints are changing cancer treatment, but their effectiveness varies and can lead to unexpected issues like hyperprogression.
  • Current animal research models, especially mice, don’t accurately reflect the human immune system and patient differences, creating a need for better models.
  • This study introduces two new antibodies that effectively target canine PD-1, offering valuable tools for canine cancer research and potential new treatments for dogs with cancer.
View Article and Find Full Text PDF

Omission of radiation therapy after breast conserving surgery for older women at low-risk of local recurrence: One option among many.

Eur J Surg Oncol

April 2024

Edinburgh Cancer Research Centre, Institute of Genetic and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.

This editorial discusses the evolving landscape of early-stage breast cancer treatment, emphasizing the need to tailor therapies based on disease biology and genomic approaches. The focus is on the reconsideration of postoperative radiation therapy (RT) for older patients with low-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Recent trials show modest long-term local recurrence rates with the omission of RT after BCS in certain cases, challenging the traditional approach.

View Article and Find Full Text PDF
Article Synopsis
  • - The study aimed to determine if adding a tumour bed boost after whole breast irradiation (WBI) improves outcomes for women with non-low-risk ductal carcinoma in situ (DCIS) post-surgery, focusing on local recurrence rates.
  • - Conducted as a phase 3 trial across 11 countries, 1,608 women participated, receiving either no boost or a boost after either conventional or hypofractionated WBI, with 6.6 years of median follow-up.
  • - Results showed the boost group had a significantly lower local recurrence rate (97.1%) compared to the no-boost group (92.7%), although the boost also led to higher reports of breast pain.
View Article and Find Full Text PDF

Objective: Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD.

Design: Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study.

View Article and Find Full Text PDF

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.

View Article and Find Full Text PDF

Systemic Influences of Mammary Cancer on Monocytes in Mice.

Cancers (Basel)

February 2022

MRC-Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.

There is a growing body of evidence that cancer causes systemic changes. These influences are most evident in the bone marrow and the blood, particularly in the myeloid compartment. Here, we show that there is an increase in the number of bone marrow, circulating and splenic monocytes by using mouse models of breast cancer caused by the mammary epithelial expression of the polyoma middle T antigen.

View Article and Find Full Text PDF

Aims/hypothesis: We assessed the real-world effect of flash monitor (FM) usage on HbA levels and diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH) rates among people with type 1 diabetes in Scotland and across sociodemographic strata within this population.

Methods: This study was retrospective, observational and registry based. Using the national diabetes registry, 14,682 individuals using an FM at any point between 2014 and mid-2020 were identified.

View Article and Find Full Text PDF
Article Synopsis
  • * Data from over 11,000 patients showed that those on infliximab and adalimumab had lower seroprevalence rates for SARS-CoV-2 compared to those on vedolizumab, indicating potential differences in immune response.
  • * Higher rates of seropositivity were found in patients with undetectable anti-TNF drug levels, suggesting that the presence of these drugs may hinder the body’s ability to produce antibodies after infection.
View Article and Find Full Text PDF

SARS-CoV-2 vaccination for patients with inflammatory bowel disease - Authors' reply.

Lancet Gastroenterol Hepatol

July 2021

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

View Article and Find Full Text PDF

Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.

Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections.

View Article and Find Full Text PDF

Aims/hypothesis: Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA.

Methods: We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure.

View Article and Find Full Text PDF

Aims/hypothesis: The aim of this work was to map the number of prescribed drugs over age, sex and area-based socioeconomic deprivation, and to examine the association between the number of drugs and particular high-risk drug classes with adverse health outcomes among a national cohort of individuals with type 1 diabetes.

Methods: Utilising linked healthcare records from the population-based diabetes register of Scotland, we identified 28,245 individuals with a diagnosis of type 1 diabetes on 1 January 2017. For this population, we obtained information on health status, predominantly reflecting diabetes-related complications, and information on the total number of drugs and particular high-risk drug classes prescribed.

View Article and Find Full Text PDF

SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement.

Lancet Gastroenterol Hepatol

March 2021

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD.

View Article and Find Full Text PDF

The proportion of samples with one or more close relatives in a genetic dataset increases rapidly with sample size, necessitating relatedness modeling and enabling pedigree-based analyses. Despite this, relatives are generally unreported and current inference methods typically detect only the degree of relatedness of sample pairs and not pedigree relationships. We developed CREST, an accurate and fast method that identifies the pedigree relationships of close relatives.

View Article and Find Full Text PDF

Disparities in the analysis of morphological disparity.

Biol Lett

July 2020

School of Earth Sciences, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, UK.

Analyses of morphological disparity have been used to characterize and investigate the evolution of variation in the anatomy, function and ecology of organisms since the 1980s. While a diversity of methods have been employed, it is unclear whether they provide equivalent insights. Here, we review the most commonly used approaches for characterizing and analysing morphological disparity, all of which have associated limitations that, if ignored, can lead to misinterpretation.

View Article and Find Full Text PDF

Objective: In 2019, the European Society of Cardiology led and released new guidelines for diabetes cardiovascular risk management, reflecting recent evidence of cardiovascular disease (CVD) reduction with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and some glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes (T2D). A key recommendation is that all those with T2D who are (antihyperglycemic) drug naïve or on metformin monotherapy should be CVD risk stratified and an SGLT-2i or a GLP-1RA initiated in all those at high or very high risk, irrespective of glycated hemoglobin. We assessed the impact of these guidelines in Scotland were they introduced as is.

View Article and Find Full Text PDF

Background: BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years.

View Article and Find Full Text PDF

Aims: To describe the association between socio-economic status and mortality in a nation-wide cohort of people with type 1 diabetes in Scotland and to compare patterns over time and with the general population.

Methods: A retrospective cohort study was performed using data for people with type 1 diabetes from a population-based register linked to mortality records. Socio-economic status was derived from quintiles of an area-based measure: the Scottish Index of Multiple Deprivation.

View Article and Find Full Text PDF

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

Am J Kidney Dis

May 2020

Primary Care & Population Sciences Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Rationale & Objective: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function.

View Article and Find Full Text PDF

Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus.

Diabetologia

March 2020

MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK.

Aims/hypothesis: The aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes.

Methods: We used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records.

View Article and Find Full Text PDF

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes.

View Article and Find Full Text PDF

Glycaemic control trends in people with type 1 diabetes in Scotland 2004-2016.

Diabetologia

August 2019

MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.

Article Synopsis
  • The study assessed changes in glycaemic control for type 1 diabetes patients in Scotland from 2004 to 2016, finding a notable improvement only in the last four years.
  • Most of the decrease in HbA levels was observed in children and adolescents, but socioeconomic status and sex differences in control did not change significantly over time.
  • Overall, while progress was made, disparities still existed based on socioeconomic status and between genders.
View Article and Find Full Text PDF

Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study.

Lancet Gastroenterol Hepatol

May 2019

Department of Gastroenterology, Royal Devon and Exeter Hospital National Health Service (NHS) Foundation Trust, Exeter, UK; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK. Electronic address:

Background: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal.

Methods: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study.

View Article and Find Full Text PDF

Aims: This study aimed to explore breast cancer patients' understanding and acceptability of implanted biosensors (BS) within the primary tumour to personalise adjuvant radiotherapy, and to determine optimal design and number of BS, and evaluate potential clinical benefits as well as concerns about tolerance, toxicity, dwell time, and confidentiality of data.

Patients And Methods: A total of 32 patients treated by surgery (29 breast conserving, 3 mastectomy), postoperative radiotherapy and systemic therapy for early breast cancer, were recruited from a posttreatment radiotherapy clinic at a cancer centre. Patients participated in semistructured interviews.

View Article and Find Full Text PDF