Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24).

A trafficking regulatory subnetwork governs αβ integrin-HER2 cross-talk to control breast cancer invasion and drug resistance.

HER2 and αβ integrin are independent predictors of breast cancer survival and metastasis. We identify an αβ/HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound αβ recruits HER2 and a trafficking subnetwork, comprising guanosine triphosphatases RAB5 and RAB7A and the Rab regulator guanine nucleotide dissociation inhibitor 2 (GDI2).

Risk management during times of health uncertainty in Spain: A qualitative analysis of ethical challenges.

The study examines the reflections of various experts in risk management when asked about uncertainty generated by a health threat and the response to such a threat: what criteria should guide action when potential harm is anticipated, but not known with certainty? The objective of the research is to obtain a holistic perspective of ethical conflicts in risk management, based on experts' accounts within the Spanish territory. A qualitative study was conducted through semi-structured interviews with 27 experts from various fields related to health risk management and its ethical implications, following the grounded theory method. The method includes theory generation through an inductive approach, based on the identified categories.

Selection of antibody-binding covalent aptamers.

Aptamers are oligonucleotides with antibody-like binding function, selected from large combinatorial libraries. In this study, we modified a DNA aptamer library with N-hydroxysuccinimide esters, enabling covalent conjugation with cognate proteins. We selected for the ability to bind to mouse monoclonal antibodies, resulting in the isolation of two distinct covalent binding motifs.

Enhanced liver fibrosis (ELF) score predicts hepatic decompensation and mortality.

Background & Aims: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway.

Methods: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited.

Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.

Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK.

Methods: Data was retrospectively collected from 16 tertiary UK cancer centres.

The impact of symptom clusters on endocrine therapy adherence in patients with breast cancer.

Background: When taken as prescribed, endocrine therapy is effective in reducing risk of recurrence and mortality in the treatment of patients with breast cancer. However, treatment side effects can act as a barrier to medication adherence. Existing research has not identified any specific side effects as consistent predictors of nonadherence.

Ethical challenges during critical phases of the COVID-19 pandemic: An interpretive synthesis.

Background: During the most critical phases of COVID-19 pandemic, dramatic situations were experienced in hospitals and care centers that nurses could hardly verbalize. Especially relevant were deep challenges related to terminal illness, situations of extreme sacrifice, as well as reflections on protective measures mixed with beliefs. We intend to analyze which problems had the greatest impact on professionals.

Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT.

Introduction And Objectives: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care.

Cardiovascular sequelae of trastuzumab and anthracycline in long-term survivors of breast cancer.

Objectives: Long-term follow-up of patients treated with trastuzumab largely focuses on those with reduced left ventricular ejection fraction (LVEF) on treatment completion. This study sought to evaluate the prevalence of cardiovascular risk factors, overt cardiovascular disease and cardiac imaging abnormalities using cardiac magnetic resonance (CMR), in participants with normal LVEF on completion of trastuzumab±anthracycline therapy at least 5 years previously.

Methods: Participants with human epidermal growth factor receptor 2-positive breast cancer treated with trastuzumab±anthracycline ≥5 years previously were identified from a clinical database.

Evaluation of relational factor in patient satisfaction with the treatment received by dental students.

Introduction: The study focused on the importance of the relational factor and empathy in the general satisfaction of patients for the treatment received by university dental students. To achieve this objective, a tool capable of evaluating the most humanistic dimensions (empathy, kindness, trust) in the development of dental treatment has been designed.

Materials And Methods: A review of the literature was carried out and, based on its findings, a questionnaire was designed to assess patient satisfaction with the dental student's empathy.

Olaparib and Ceralasertib (AZD6738) in Patients with Triple-Negative Advanced Breast Cancer: Results from Cohort E of the plasmaMATCH Trial (CRUK/15/010).

Purpose: Approximately 10% to 15% of triple-negative breast cancers (TNBC) have deleterious mutations in BRCA1 and BRCA2 and may benefit from PARP inhibitor treatment. PARP inhibitors may also increase exogenous replication stress and thereby increase sensitivity to inhibitors of ataxia telangiectasia and Rad3-related (ATR) protein. This phase II study examined the activity of the combination of PARP inhibitor, olaparib, and ATR inhibitor, ceralasertib (AZD6738), in patients with advanced TNBC.

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

Background: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy.

Methods: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment.

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program.

Background: The Ibrance® Patient Program was established to provide access to palbociclib for UK National Health Service (NHS) patients with metastatic breast cancer (MBC), pending a funding decision.

Methods: Non-interventional cohort study involving a retrospective medical record review of patients commenced on palbociclib between April and December 2017 at eight UK centres. Primary outcomes included clinicopathological characteristics, treatment patterns, clinical outcomes and selected adverse events.

Laying the foundations for hepatitis C elimination: evaluating the development and contribution of community care pathways to diagnostic efforts.

Background: Hepatitis C Virus (HCV) is a public health threat which contributes substantially to the global burden of liver disease. There is much debate about effective approaches to scaling up diagnosis of HCV among risk groups. Tayside, a region in the East of Scotland, developed low-threshold community pathways for HCV to lay the foundations of an elimination strategy.

Identification of liver disease: why and how.

Mortality from chronic liver disease (CLD) in the UK has increased by over 400% since 1970, driven by alcohol, non-alcoholic fatty liver disease and hepatitis C virus, the natural histories of which can all be improved by early intervention. Patients often present with advanced disease, which would be preventable if diagnosed earlier and lifestyle change opportunities offered. Liver function tests (LFTs) are very commonly measured.

A phase IB and randomised phase IIA trial of CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases: CARBON trial results.

Background: Approximately 70% of patients with metastatic breast cancer (MBC) develop bone metastases. Despite advances in systemic treatment options and the use of bone targeted agents in the management of bone metastases to reduce skeletal morbidity, there remains an unmet need for further treatment options. Radium-223 (Ra) is an alpha-emitting radiopharmaceutical that is preferentially taken up into bone at sites of increased osteoblastic activity where it emits high-energy, short-range alpha-particles that could provide a targeted anti-tumour effect on bone metastases.

A randomised controlled trial of interventions for taxane-induced nail toxicity in women with early breast cancer.

Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures.

Rationale and Design of the Cardiac CARE Trial: A Randomized Trial of Troponin-Guided Neurohormonal Blockade for the Prevention of Anthracycline Cardiotoxicity.

Background: Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients.

Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.

We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment.

Improving care for patients in the outlying wards: Lessons from patients' care experience.

Importance: Overcrowding in hospitals and lack of capacity in general medical wards can result in a medical patient being transferred to other specialty wards often referred as 'outlying' or 'boarding' wards.

Objectives: We explored the experiences of our outlying patients to identify local factors that affect their care experience and inform interventions that could improve their care deliveries and outcomes.

Design, Setting, And Participants: Qualitative interviews using semi-structured questions were conducted in 21 medical patients from a mixture of specialty wards in a large tertiary NHS hospital.