Circulating Fibronectin Controls Tumor Growth

Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF) retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.     

Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management

Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as “diabetic cardiomyopathy.” Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition.     

Risk resistance: constructing home birth as morally responsible on an online discussion group

In hegemonic risk discourses, hospital obstetric units are represented as the safest and best birth settings; however, a minority of women in England and Wales (2.3% in 2014) still opt for home birth. In this article, I analyse pro-home birth discourses on a UK-based online discussion group for pregnant women covering the period 2010–2015 and collected in March 2016, to identify how individuals making pro-home birth posts on the site represented home birth as a morally responsible choice. Using Foucauldian discourse analysis, I identify three main themes: home births as a normal process, representing an intimate, existential life moment which meets women’s needs for care and personal autonomy, and is convenient and relatively safe, in contrast to hospital births which are characterised as risky; home births as morally legitimate and justified by discourses of evidence-based risk assessment, woman centredness and empowerment; and home birth as not risky and the mothers who opt for it were not taking unnecessary risks but were acting responsibly. In this article, I examine the ways in which the online setting can be used to resist dominant risk discourses. I show how the participants in the online discussion group in my study used available discursive resources to challenge hegemonic risk discourses regarding birth setting, making resistance to dominant risk discourses possible, as pro-home birth discourses legitimised ‘nonconformist’ decisions regarding birth setting. The focus on the ‘risk-takers’ in this article is valuable for healthcare practitioners seeking to improve their communication about birth setting choices with pregnant women.     

The reliability of clinical judgments and criteria associated with mechanisms-based classifications of pain in patients with low back pain disorders: a preliminary reliability study

Mechanisms-based classifications of pain have been advocated for their potential to aid understanding of clinical presentations of pain and improve clinical outcomes. However, the reliability of mechanisms-based classifications of pain and the clinical criteria upon which such classifications are based are not known. The purpose of this investigation was to assess the inter- and intra-examiner reliability of clinical judgments associated with: (i) mechanisms-based classifications of pain; and (ii) the identification and interpretation of individual symptoms and signs from a Delphi-derived expert consensus list of clinical criteria associated with mechanisms-based classifications of pain in patients with low back (±leg) pain disorders. The inter- and intra-examiner reliability of an examination protocol performed by two physiotherapists on two separate cohorts of 40 patients was assessed. Data were analysed using kappa and percentage of agreement values. Inter- and intra-examiner agreement associated with clinicians’ mechanisms-based classifications of low back (±leg) pain was ‘substantial’ (kappa  = 0.77; 95% confidence interval (CI): 0.57–0.96; % agreement  = 87.5) and ‘almost perfect’ (kappa  = 0.96; 95% CI: 0.92–1.00; % agreement = 92.5), respectively. Sixty-eight and 95% of items on the clinical criteria checklist demonstrated clinically acceptable (kappa ⩾ 0.61 or % agreement ⩾ 80%) inter- and intra-examiner reliability, respectively. The results of this study provide preliminary evidence supporting the reliability of clinical judgments associated with mechanisms-based classifications of pain in patients with low back (±leg) pain disorders. The reliability of mechanisms-based classifications of pain should be investigated using larger samples of patients and multiple independent examiners.     

Percutaneous endovascular occlusion of symptomatic coronary arteriovenous fistulas with cyanoacrylate

We describe four cases with symptomatic coronary artery fistulas that were treated primarily with endovascular cyanoacrylate embolization. Coils were also used as adjunctive embolic agents in two of these cases. All four cases showed symptomatic improvement after closure of the fistulas. Complications occurred in three cases including transient ST-segment elevation in one, symptomatic pulmonary embolization in a second, and transient pleuritic chest pain, pericarditis and acute renal failure in a third. The technical aspects of all four cases are given together with a review of the use of cyanoacrylate as an embolic material. We conclude that cyanoacrylate embolization could be considered as an alternative technique for the endovascular closure of coronary artery fistulas but must also caution that the use of this embolic agent is hazardous and should be restricted to practitioners experienced in its usage.     

Development and Validation of the Primary Care Team Dynamics Survey

ObjectiveTo develop and validate a survey instrument designed to measure team dynamics in primary care.ConclusionsIt is possible to measure primary care team dynamics reliably using a 29-item survey. This survey may be used in ambulatory settings to study teamwork and explore the effect of efforts to improve team-based care. Future studies should demonstrate the importance of team dynamics for markers of team effectiveness (e.g., work satisfaction, care quality, clinical outcomes).     

A Randomized Controlled Trial of Intensive Care Management for Disabled Medicaid Beneficiaries with High Health Care Costs

ObjectiveTo evaluate outcomes of a registered nurse–led care management intervention for disabled Medicaid beneficiaries with high health care costs.ConclusionsWe found no health care cost savings for disabled Medicaid beneficiaries randomized to intensive care management. Among participants, care management may have the potential to increase access to needed care, slow growth in the number and therefore cost of unplanned hospitalizations, and prevent homelessness. These findings apply to start-up care management programs targeted at high-cost, high-risk Medicaid populations.     

Angled views in the evaluation of the right coronary artery

The use of cranial and caudal angulated views in the angiographic evaluation of the right coronary artery (RCA) was assessed in 61 patients. Each patient had a standard LAO and RAO view, followed by one or more angled views. The standard LAO view showed the area about the origin of the posterior descending artery (PD₀) adequately in 33 of 46 patients (72% ), and the mid and distal portions of the posterior descending artery (PD_m&d) adequately in 26/46 (56% ). The standard RAO view showed the PD₀ adequately in only 17/46 (37% ) and the PD_m&d adequately in 41/46 (89% ). With the LAO cranial view, however, the PD₀ was seen well in 45/46 (98% ), and PD_m&d was seen well in 44/46 (96% ). The RAO angled views, although of more limited utility, also afforded improved visualization of the distal segments of the RCA. We recommend the use of angled views in the evaluation of the right coronary artery, as these views, particularly the LAO cranial view, afford improved visualization of the distal segments of the RCA.     

Vasculopathy of the large arteries in children infected by the human immune deficiency virus

We report on two children with advanced acquired immune deficiency syndrome presenting with vasculopathy involving the large vessels. Both patients had extensive involvement of the aorta and its branches. One patient presented with heart failure, and mild systemic hypertension secondary to renal arterial stenosis, while the other patient manifested with gangrene of both arms.