Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.     

How physiotherapists perceive,interpret, and respond to the ethical dimensions of practice: A qualitative study

The profile and reach of physiotherapy has expanded in areas of extended scope of practice, and broader engagement with population needs beyond the individual treatment encounter. These changes raise increasingly complex ethical challenges evidenced by growth in physiotherapy-based ethics studies and discussions. This paper examines how a broad cross section of Australian physiotherapists perceive, interpret, and respond to ethical challenges in their work contexts and how professional codes of conduct are used in their practice. Using an interpretive qualitative methodology, purposive sampling of 88 members of national clinical special interest groups were recruited for focus group discussions. Narrative-based and thematic data analysis identified ethical challenges as emerging from specific clinical contexts, and influenced by health organizations, funding policies, workplace relationships, and individually held perspectives. Five themes were developed to represent these findings: (1) the working environment, (2) balancing diverse needs and expectation, (3) defining ethics, (4) striving to act ethically, and (5) talking about ethics. The results portray a diverse and complex ethical landscape where therapists encounter and grapple with ethical questions emerging from the impact of funding models and policies affecting clinical work, expanding boundaries and scope of practice and changing professional roles and relationships. Codes of conduct were described as foundational ethical knowledge but not always helpful for “in the moment” ethical decision-making. Based on this research, we suggest how codes of conduct, educators, and professional associations could cultivate and nurture ethics capability in physiotherapy practitioners for these contemporary challenges.     

Leptin, lipid and lipid metabolism-related hormones in chronic renal failure in Arabia

SUMMARY: In patients with chronic renal failure (CRF), hyperleptinaemia has been widely reported, but the exact mechanisms leading to elevated leptin levels are unclear. Impaired renal clearance of leptin and the influence of other hormones may be important. In this study, we measured serum leptin levels in 150 patients on haemodialysis, peritoneal dialysis or in the predialysis phase of CRF. Furthermore, we measured plasma levels of insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as plasma levels of triacylglycerols and total low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol. We observed significantly elevated levels of leptin, particularly in female patients, and leptin was shown to correlate significantly with insulin, total and LDL-cholesterol and log triacylglycerols. Leptin was inversely correlated with GH concentrations, but was not correlated with IGF-1 levels. Despite the multiple correlations established between leptin levels and other variables, only hyperinsulinaemia in CRF seems to be important as a determinator of leptin levels.     

Multi-detector CT angiography for lower gastrointestinal bleeding: Can it select patients for endovascular intervention?

This is a retrospective review of the results at our institution of using multi-detector CT angiography (CTA) to localise lower gastrointestinal (GI) bleeding. We hypothesised that in our patient population: (i) CTA was unlikely to demonstrate bleeding in patients who were haemodynamically stable; (ii) in haemodynamically unstable patients in whom CTA was undertaken, the results could be used to select patients who would benefit from catheter angiography; and (iii) in haemodynamically unstable patients in whom CTA was undertaken, a subgroup of patients could be identified who would benefit from primary surgical treatment, avoiding invasive angiography completely. A retrospective review was conducted of the clinical records of all patients undergoing CTA for lower GI haemorrhage at our institution between 1 January 2005 and 30 June 2007. Out of the 20 patients examined, 10 had positive CTAs demonstrating the bleeding site. Nine were haemodynamically unstable at the time of the study. Four patients with positive CT angiograms were able to be treated directly with surgery and avoided invasive angiography. Ten patients had negative CTAs. Four of these were haemodynamically unstable, six haemodynamically stable. Only one required intervention to secure haemostasis, the rest stopped spontaneously. No haemodynamically stable patient who had a negative CTA required intervention. CTA is a useful non-invasive technique for localising the site of lower GI bleeding. In our patient population, in the absence of haemodynamic instability, the diagnostic yield of CTA was low and bleeding was likely to stop spontaneously. In haemodynamically unstable patients, a positive CTA allowed patients to be triaged to surgery or angiography, whereas there was a strong association between a negative CTA and spontaneous cessation of bleeding.     

Physical Therapy and Complementary and Alternative Medicine: An Educational Tool for Enhancing Integration

In an outpatient rehabilitation setting, both patients’ use and therapists’ knowledge of complementary and alternative medicine (CAM) varies widely. Based on this observation and a recognition of CAM as an emerging practice area for rehabilitation professionals, it was felt that a thorough and consistent approach to the education and orientation of physical therapists to the world of CAM and integrative care was needed. This special interest paper will describe one center’s approach, development, and use of a unique and comprehensive training manual designed to provide both a structured and standardized approach for educating physical therapists about CAM and related therapeutic modalities. This innovative teaching tool allows for multiple methods of content delivery within a multidisciplinary format and can be used for those who practice currently or desire to practice in an integrative care environment.     

Evaluation of clinical outcomes in anterior cruciate ligament surgery

Clinical outcomes data can be used to facilitate patient management decisions, assess clinician and organizational performance, and to provide evidence for the effectiveness of surgery and rehabilitation. The validity of the inferences made from outcomes data are dependent on the validity of the outcomes measures themselves and the circumstances under which the data were collected, analyzed, and interpreted. Clinical outcomes may include measures of impairment of body structure and function, activity limitation, and participation restriction. However, because the relationship between impairment and the resulting activity limitation and participation restriction is not direct, and because activity limitations and participation restrictions are of the utmost concern to the athlete, the primary clinical outcome should be measures of activity limitation and participation restriction. Activity limitation and participation restriction may be measured either through direct observation of performance or by general or specific measures of health related quality of life. Clinical outcomes data must be collected systematically to ensure valid inferences from the data.     

Cell biology of smooth muscle in culture: implications for atherogenesis

Smooth muscle cells are one of the most important, if not the most important component of atheromatous plaque. Smooth muscle cells from developing and regenerating arteries, as well as atheromatous plaques, show similar morphological and biochemical characteristics which differ from adult tissue. During primary culture, adult smooth muscle cells alter their morphology to resemble those of the developing, regenerating and atheromatous material. We propose that primary cell culture of smooth muscle cells provides a model for the study of smooth muscle cell changes during atheroma formation.