Comprehensive Geriatric Assessment in Men Aged 70 Years or Older with Localised Prostate Cancer Undergoing Radical Radiotherapy.

Aims: Treatment decisions for men aged 70 years or over with localised prostate cancer need to take into account the risk of death from competing causes and fitness for the proposed treatment. Objective assessments such as those included in a comprehensive geriatric assessment (CGA) might help to inform the decision-making process. The aim of this study was to describe the CGA scores of a cohort of older men with prostate cancer, evaluate potential screening tools in this population and assess whether any CGA component predicts significant acute radiotherapy toxicity.

PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity.

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma.

Statistical reporting of clinical pharmacology research.

Research in clinical pharmacology covers a wide range of experiments, trials and investigations: clinical trials, systematic reviews and meta-analyses of drug usage after market approval, the investigation of pharmacokinetic-pharmacodynamic relationships, the search for mechanisms of action or for potential signals for efficacy and safety using biomarkers. Often these investigations are exploratory in nature, which has implications for the way the data should be analysed and presented. Here we summarize some of the statistical issues that are of particular importance in clinical pharmacology research.

Postural and cortical responses following visual occlusion in standing and sitting tasks.

Perturbation-evoked responses (PERs) to a physical perturbation of postural stability have been detected using electroencephalography (EEG). Components of these responses are hypothesized to demonstrate the detection (P1) and evaluation (N1) of postural instability. Despite the important contribution of the visual system to postural control, PERs to a visual perturbation of posture have yet to be reported.

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling.

Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells.

[Chemotherapy in the Elderly with Non-Small Cell Lung Cancer: A Non-Interventional, Prospective, Multicentric Observational Study].

 Elderly patients (70 years or older) with non-small cell lung cancer (NSCLC) do benefit from systemic chemotherapy as shown in many studies. We prospectively collected multicentric data on therapeutic decisions from patients 70 years or older to reflect the reality in the German health care system.  Patients 70 years or older with NSCLC Stage IIIB or IV were eligible.

Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy.

Background: Mesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural inhabitants in Central America. We have previously described the renal morphology in 8 patients from El Salvador. To confirm the renal pathology, we have studied kidney biopsies from patients with MeN in Nicaragua.

Practical Immuno-PET Radiotracer Design Considerations for Human Immune Checkpoint Imaging.

Immune checkpoint blockade has emerged as a promising cancer treatment paradigm. Unfortunately, there are still a large number of patients and malignancies that do not respond to therapy. A major barrier to validating biomarkers for the prediction and monitoring of responders to clinical checkpoint blockade has been the lack of imaging tools to accurately assess dynamic immune checkpoint expression.

Cardiopulmonary Exercise Testing in Fontan Patients With and Without Isomerism (Heterotaxy) as Compared to Patients With Primary Ciliary Dyskinesia and Subjects With Structurally Normal Hearts.

Isomerism, also known as heterotaxy, is a clinical entity that impacts multiple organ systems both anatomically and functionally. The airways and lungs are involved in a great number of these patients, leading to increased sinopulmonary symptoms, increased need for oxygenation, and increased postoperative ventilatory support. Additionally, these patients often have congenital heart disease requiring Fontan palliation.

Eradication of Canine Diffuse Large B-Cell Lymphoma in a Murine Xenograft Model with CD47 Blockade and Anti-CD20.

Cancer immunotherapies hold much promise, but their potential in veterinary settings has not yet been fully appreciated. Canine lymphomas are among the most common tumors of dogs and bear remarkable similarity to human disease. In this study, we examined the combination of CD47 blockade with anti-CD20 passive immunotherapy for canine lymphoma.

Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study.

Background: The CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI.

Methods: The Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease.

ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

Background: There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy.

Methods: Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts.

A Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio ) in cardiac surgery: the REVAKI-1 study.

Aims: Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. There is no effective prevention or treatment. Sildenafil citrate (Revatio , Pfizer Inc.

Improving outcomes for older women with gynaecological malignancies.

The incidence of most gynaecological malignancies rises significantly with increasing age. With an ageing population, the proportion of women over the age of 65 with cancer is expected to rise substantially over the next decade. Unfortunately, survival outcomes are much poorer in older patients and evidence suggests that older women with gynaecological cancers are less likely to receive current standard of care treatment options.

Structure and Dynamics of PD-L1 and an Ultra-High-Affinity PD-1 Receptor Mutant.

The immune checkpoint receptor PD-1 and its ligand, PD-L1, have emerged as key regulators of anti-tumor immunity in humans. Recently, we reported an ultra-high-affinity PD-1 mutant, termed high-affinity consensus (HAC) PD-1, which shows superior therapeutic efficacy in mice compared with antibodies. However, the molecular details underlying the action of this agent remain incompletely understood, and a molecular view of PD-1/PD-L1 interactions in general is only beginning to emerge.

Rates of major complications during neoadjuvant and adjuvant chemotherapy for early breast cancer: An off study population.

Objectives: To determine the incidence and risk factors for thromboembolic events (TE) and febrile neutropenia (FN) in patients receiving systemic chemotherapy for early breast cancer (EBC).

Methods: 325 patients received FEC, FEC-T or ECaP for EBC in 2013.

Results: TE occurred in 7.

Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy.

Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti-c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice.

CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer.

Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment.

Soft tissue sarcomas of the distal lower extremities: A single-institutional analysis of the prognostic significance of surgical margins in 120 patients.

Soft tissue sarcomas (STS) arising in the distal lower extremities pose a therapeutic challenge due to concerns of functional morbidity. The impact of surgical margins on local recurrence‑free survival (LRFS) and overall survival (OS) still remains controversial. The aim of this study was to identify prognostic indicators of survival and functional outcome in patients with STS of the distal lower extremities through a long‑term follow‑up.

Cluster randomised trial of a tailored intervention to improve the management of overweight and obesity in primary care in England.

Background: Tailoring is a frequent component of approaches for implementing clinical practice guidelines, although evidence on how to maximise the effectiveness of tailoring is limited. In England, overweight and obesity are common, and national guidelines have been produced by the National Institute for Health and Care Excellence. However, the guidelines are not routinely followed in primary care.

Reconstruction of Soft-Tissue Defects at the Foot and Ankle after Oncological Resection.

Introduction: Solid malignancies at the foot and ankle region are rare and include mainly soft-tissue sarcomas, bone sarcomas, and skin malignancies. Complete surgical resection with clear margins still remains the mainstay of therapy in these malignancies. However, attainment of negative surgical margins in patients with locally advanced tumors of the foot and ankle region may require extensive surgery and could result in loss of extremity function.

Trial protocol for a randomised controlled trial of red cell washing for the attenuation of transfusion-associated organ injury in cardiac surgery: the REDWASH trial.

Introduction: It has been suggested that removal of proinflammatory substances that accumulate in stored donor red cells by mechanical cell washing may attenuate inflammation and organ injury in transfused cardiac surgery patients. This trial will test the hypotheses that the severity of the postoperative inflammatory response will be less and postoperative recovery faster if patients undergoing cardiac surgery receive washed red cells compared with standard care (unwashed red cells).

Methods And Analysis: Adult (≥16 years) cardiac surgery patients identified at being at increased risk for receiving large volume red cell transfusions at 1 of 3 UK cardiac centres will be randomly allocated in a 1:1 ratio to either red cell washing or standard care.

A new in vivo model using a dorsal skinfold chamber to investigate microcirculation and angiogenesis in diabetic wounds.

Introduction: Diabetes mellitus describes a dysregulation of glucose metabolism due to improper insulin secretion, reduced insulin efficacy or both. It is a well-known fact that diabetic patients are likely to suffer from impaired wound healing, as diabetes strongly affects tissue angiogenesis. Until now, no satisfying in vivo murine model has been established to analyze the dynamics of angiogenesis during diabetic wound healing.