The fibrotic and immune microenvironments as targetable drivers of metastasis

Although substantial progress has been made over the past 40 years in treating patients with cancer, effective therapies for those who are diagnosed with advanced metastatic disease are still few and far between. Cancer cells do not exist in isolation: rather, they exist within a complex microenvironment composed of stromal cells and extracellular matrix. Within this tumour microenvironment exists an interplay between the two main stromal cell subtypes, cancer-associated fibroblasts (CAFs) and immune cells, that are important in controlling metastasis. A complex network of paracrine signalling pathways between CAFs, immune cells and tumour cells are involved at multiple stages of the metastatic process, from invasion and intravasation at the primary tumour site to extravasation and colonisation in the metastatic site. Heterogeneity and plasticity within stromal cell populations also contribute to the complexity. Although many of these processes are likely to be common to a number of metastatic sites, we will describe in detail the interplay within the liver, a preferred site of metastasis for many tumours. A greater understanding of these networks provides opportunities for the design of new therapeutic approaches for targeting the metastatic disease.Subject terms: Cancer microenvironment, Mechanisms of disease     

Patellofemoral joint arthroplasty: patient selection,surgical technique and outcomes

Isolated patellofemoral arthritis is an increasingly recognized entity, and is usually associated with previous patellofemoral dysplasia or instability. Patellofemoral arthroplasty (PFA) has evolved significantly in recent years, both in terms of implant design and importantly in the understanding of appropriate patient selection. This review outlines the indications and investigations for PFA, provides a brief history of the development of contemporary implants, and presents the clinical outcomes for the prostheses most commonly used in the UK. In addition, it provides a detailed surgical technique for implantation of an onlay implant, with tips on how to optimize patellofemoral biomechanics and thus achieve a consistently good outcome.     

Planning for Chaos: Developing the Concept of Emergency Preparedness through the Experience of the Paramedic

ObjectiveEmergency preparedness is a developing specialty with a limited evidence base. Published literature primarily offers a retrospective view of experience, with few studies examining and understanding the individual lived experience of practitioners prospectively. This study explores paramedics’ lived experience of emergency preparedness and applies that learning.MethodsThirteen paramedics were recruited through purposive sampling. Face-to-face semi-structured interviews explored their individual experiences of emergency preparedness, in line with the idiographic focus of Interpretative Phenomenological Analysis.ResultsThrough data analysis, the following superordinate themes were identified for further discussion: self-determination, control, and experience-based practice. Participants appeared to value their role and the unpredictable environment in which they worked. Personal resilience, an area that they suggested is not covered effectively within individual preparation, was viewed as important. The participants articulated that risk, threat, uncertainty, safety, trust, and control were important concepts within individual preparedness. These paramedics valued practice-based knowledge and education as credible and transferrable to their clinical work.ConclusionEvidence from this study suggests that standard emergency preparedness, with the focus at organizational level, is not sufficient for the individual workers or for an overall effective response. Dimensions of individual preparedness are presented, with the paramedic central to the experience within a conceptual model (the DiEP model), creating a new form of emergency preparedness that reflects the individual paramedic’s experience.     

Informed Consent for Medical Research: Common Discrepancies and Readability

Objective: To identify common discrepancies and average reading grade levels for informed consent forms (ICFs) us submitted to institutional review boards (IRBs) by medical researchers.
Methods: A retrospective evaluation of ICFs as submitted to IRBs of 3 university-affiliated hospitals during a I-year period. ICF content was evaluated using a checklist of 23 requirements specified in the federal regulations governing human research. Documents then were computer-analyzed to determine the readability scores using 2 common indexes of comprehension. A discrepancy was defined as any instance in which an ICF did not address an applicable requirement in the Code of Federal Regulations.
Results: Eighty-two ICFs representing 16 medical specialties were evaluated; 8 (10%) were from emergency medicine. Eighteen ICFs (22%) were conspicuously incomplete, lacking 29 federal requirements. The mean number of discrepancies was 4.7 (95% CI, 3.9–5.5) Common omissions included: a statement about who is doing the research, number of subjects in the study, circumstances when a subject's participation may be terminated, disclosure of alternative procedures, and notice to subjects regarding new findings. The mean Flesch grade level required to read all ICFs was 13.8 (95% CI, 13.5–14.2), implying that the majority of the U.S. adult population would be unable to comprehend these forms.
Conclusion: Designing a consent form to meet all of the federal requirements while maintaining a level of reading comprehension suitable for the general population is a difficult task for investigators.