BackgroundBetaine is a major osmolyte, also important in methyl group metabolism. Concentrations of betaine, its metabolite dimethylglycine and analog trimethylamine-N-oxide (TMAO) in blood are cardiovascular risk markers. Diabetes disturbs betaine: does diabetes alter associations between betaine-related measures and cardiovascular risk?MethodsPlasma samples were collected from 475 subjects four months after discharge following an acute coronary admission. Death (n = 81), secondary acute MI (n = 87), admission for heart failure (n = 85), unstable angina (n = 72) and all cardiovascular events (n = 283) were recorded (median follow-up: 1804 days).ResultsHigh and low metabolite concentrations were defined as top or bottom quintile of the total cohort. In subjects with diabetes (n = 79), high plasma betaine was associated with increased frequencies of events; significantly for heart failure, hazard ratio 3.1 (1.2–8.2) and all cardiovascular events, HR 2.8 (1.4–5.5). In subjects without diabetes (n = 396), low plasma betaine was associated with events; significantly for secondary myocardial infarction, HR 2.1 (1.2–3.6), unstable angina, HR 2.3 (1.3–4.0), and all cardiovascular events, HR 1.4 (1.0–1.9). In diabetes, high TMAO was a marker of all outcomes, HR 2.7 (1.1–7.1) for death, 4.0 (1.6–9.8) for myocardial infarction, 4.6 (2.0–10.7) for heart failure, 9.1 (2.8–29.7) for unstable angina and 2.0 (1.1–3.6) for all cardiovascular events. In subjects without diabetes TMAO was only significant for death, HR 2.7 (1.6–4.8) and heart failure, HR 1.9 (1.1–3.4). Adding the estimated glomerular filtration rate to Cox regression models tended to increase the apparent risks associated with low betaine.ConclusionsElevated plasma betaine concentration is a marker of cardiovascular risk in diabetes; conversely low plasma betaine concentrations indicate increased risk in the absence of diabetes. We speculate that the difference reflects control of osmolyte retention in tissues. Elevated plasma TMAO is a strong risk marker in diabetes.

Tumors are complex ecosystems composed of networks of interacting 'normal' and malignant cells. It is well recognized that cytokine-mediated cross-talk between normal stromal cells, including cancer-associated fibroblasts (CAFs), vascular endothelial cells, immune cells, and cancer cells, influences all aspects of tumor biology. Here we demonstrate that the cross-talk between CAFs and cancer cells leads to enhanced growth of oncolytic virus (OV)-based therapeutics. Transforming growth factor-β (TGF-β) produced by tumor cells reprogrammed CAFs, dampened their steady-state level of antiviral transcripts and rendered them sensitive to virus infection. In turn, CAFs produced high levels of fibroblast growth factor 2 (FGF2), initiating a signaling cascade in cancer cells that reduced retinoic acid-inducible gene I (RIG-I) expression and impeded the ability of malignant cells to detect and respond to virus. In xenografts derived from individuals with pancreatic cancer, the expression of FGF2 correlated with the susceptibility of the cancer cells to OV infection, and local application of FGF2 to resistant tumor samples sensitized them to virotherapy both in vitro and in vivo. An OV engineered to express FGF2 was safe in tumor-bearing mice, showed improved therapeutic efficacy compared to parental virus and merits consideration for clinical testing.

Summary COPD is a common and under-diagnosed disease which is increasing in prevalence worldwide. A more aggressive and optimistic approach must be adopted towards its management in primary care. This IPCRG Guideline on the management of COPD in primary care is fully consistent with GOLD guidelines. It highlights the goals of COPD treatment and the need for spirometric testing to make the diagnosis. It covers the classification of the disease according to disease severity, non-pharmacologic therapy including smoking cessation, avoidance of risk factors, patient education, pharmacologic therapy including the use of oxygen treatment, the management of exacerbations, the role of pulmonary rehabilitation, and the need for monitoring and ongoing care for COPD patients.

SummaryAims: To assess current levels of asthma control and to identify barriers to optimal asthma management. Methods: A survey was conducted of 802 asthma patients (via computer-aided telephone interviewing) and 809 general practitioners (GPs; via the internet) from the UK, Italy, France, Germany, Spain, Canada and Australia. Results: Over three-quarters (82%) of patients surveyed reported an absence of asthma control, with the vast majority (80%) experiencing subsequent lifestyle restrictions. Although most (58%) GPs questioned believed that total asthma control was possible, half (52%) agreed that their patients were not achieving best possible asthma control. Conclusions: Action is required to encourage patients to view their asthma more seriously and to be more proactive in reporting symptoms to their GP. These actions, coupled with greater prompting of patients by GPs about their asthma, should help to optimize asthma management.

The aim of this review is to discuss the role of the primary care team in the early diagnosis and effective management of COPD, and to outline education initiatives and management strategies that can be implemented in primary care.