An optimised patient-derived explant platform for breast cancer reflects clinical responses to chemotherapy and antibody-directed therapy.

Breast Cancer is the most common cancer among women globally. Despite significant improvements in overall survival, many tumours are refractory to therapy and so novel approaches are required to improve patient outcomes. We have evaluated patient-derived explants (PDEs) as a novel preclinical platform for breast cancer (BC) and implemented cutting-edge digital pathology and multi-immunofluorescent approaches for investigating biomarker changes in both tumour and stromal areas at endpoint.

Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.

Background: There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery.

Methods: Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models.

Results: A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included.

Efficacy of a personalised activity plan for BREAKing UP sitting time in patients with intermittent claudication (the BREAK UP study).

Introduction: The aim of this study was to investigate the concept of an 8-week personalised activity plan, using short periods of physical activity to break up sitting time in people with Intermittent Claudication (IC), to improve walking ability, and reduce time spent sitting.

Methods: The study was designed as a single centre, single arm, before and after study and is registered with clinicaltrials.gov (NCT04572737).

Are major lower extremity amputations well recorded in primary care electronic health records?: Insights from primary care electronic health records in England.

Aims: Major lower extremity amputations (MLEAs) are understood to be well recorded in secondary care in England in the Hospital Episode Statistics (HES) database. It is unclear how well MLEAs are recorded in primary care databases.

Background: This study compared MLEA event case ascertainment in Clinical Practice Research Datalink (CPRD) to that in HES.

Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements.

Selective protein kinase C inhibition switches time-dependent glucose cardiotoxicity to cardioprotection.

Hyperglycaemia at the time of myocardial infarction has an adverse effect on prognosis irrespective of a prior diagnosis of diabetes, suggesting glucose is the damaging factor. In models of ischaemia, we demonstrated that deleterious effects of acutely elevated glucose are PKCα/β-dependent, and providing PKCα/β are inhibited, elevated glucose confers cardioprotection. Short pre-treatments with high glucose were used to investigate time-dependent glucose cardiotoxicity, with PKCα/β inhibition investigated as a potential mechanism to reverse the toxicity.

Urinary extracellular vesicles and micro-RNA as markers of acute kidney injury after cardiac surgery.

We hypothesised that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. The study was performed in the cohort of the REVAKI-2 trial. Urine samples were collected before and 24 h after the procedure from 94 cardiac surgery patients.

Effect of high-pain versus low-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis.

Background: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC).

Methods: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched.

Gene and metabolite expression dependence on body mass index in human myocardium.

We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence.

Change in Insulin Sensitivity and Lipid Profile After Dopamine Agonist Therapy in Patients With Prolactinoma.

Background Prolactinomas are prolactin(PRL)-secreting neoplastic lesions that can lead to metabolic disturbances and insulin resistance. We aimed to find the change in insulin sensitivity and lipid profile in prolactinoma patients after dopamine therapy.  Methodology A prospective observational study was conducted at the Hayatabad Medical Complex, Peshawar between June 2019 to July 2020.

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.

Methods: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.

Experience with the Crescent cannula for adult respiratory VV ECMO: a case series.

Introduction: The Crescent is a recently introduced dual lumen cannula by which veno-venous extracorporeal membrane oxygenation (VV ECMO) is delivered. It has a number of features that enhance its ease of placement, pressure-flow dynamics and may reduce catheter-related complication rates.

Methods: We present the first case series of its kind analysing this device by means of a retrospective observational study of prospectively collected data from the first year of its use in a high volume severe acute respiratory failure centre (Glenfield, UK).

Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer.

Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective.

Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

Background: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice.

Bridging the age gap in breast cancer: impact of omission of breast cancer surgery in older women with oestrogen receptor-positive early breast cancer on quality-of-life outcomes.

Background: Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy.

Methods: This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer.

Evaluating the use of a mobile device for detection of atrial fibrillation in primary care.

A trial fibrillation (AF) increases cardio-embolic stroke risk, yet AF diagnosis and subsequent prophylactic anticoagulant prescription rates are suboptimal globally. This project aimed to increase AF diagnosis and subsequent anticoagulation prescription rates in East Midlands Clinical Commissioning Groups (CCGs). This service improvement evaluation of the East Midlands AF Advance programme investigated the implementation of mobile AF detection devices (Kardia, AliveCor) into primary-care practices within East Midlands CCGs, along with audit tools and clinician upskilling workshops designed to increase AF diagnosis and anticoagulation prescription rates.

Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life.

Background: Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET.

Methods: Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer.

Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies Evaluating Point-of-Care Tests of Coagulopathy in Cardiac Surgery.

Treatment guidelines recommend the routine use of point-of-care diagnostic tests for coagulopathy in the management of cardiac surgery patients at risk of severe bleeding despite uncertainty as to their diagnostic accuracy. We performed a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of viscoelastometry, platelet function tests, and modified thromboelastography (TEG) tests, for coagulopathy in cardiac surgery patients. The reference standard included resternotomy for bleeding, transfusion of non-red cell components, or massive transfusion.