The Metastatic Spine Disease Multidisciplinary Working Group Algorithms

The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.

Implications for Practice:

The Metastatic Spine Disease Multidisciplinary Working Group algorithms can facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation.     

Risk-Taking in Disorders of Natural and Drug Rewards: Neural Correlates and Effects of Probability,Valence, and Magnitude

Pathological behaviors toward drugs and food rewards have underlying commonalities. Risk-taking has a fourfold pattern varying as a function of probability and valence leading to the nonlinearity of probability weighting with overweighting of small probabilities and underweighting of large probabilities. Here we assess these influences on risk-taking in patients with pathological behaviors toward drug and food rewards and examine structural neural correlates of nonlinearity of probability weighting in healthy volunteers. In the anticipation of rewards, subjects with binge eating disorder show greater risk-taking, similar to substance-use disorders. Methamphetamine-dependent subjects had greater nonlinearity of probability weighting along with impaired subjective discrimination of probability and reward magnitude. Ex-smokers also had lower risk-taking to rewards compared with non-smokers. In the anticipation of losses, obesity without binge eating had a similar pattern to other substance-use disorders. Obese subjects with binge eating also have impaired discrimination of subjective value similar to that of the methamphetamine-dependent subjects. Nonlinearity of probability weighting was associated with lower gray matter volume in dorsolateral and ventromedial prefrontal cortex and orbitofrontal cortex in healthy volunteers. Our findings support a distinct subtype of binge eating disorder in obesity with similarities in risk-taking in the reward domain to substance use disorders. The results dovetail with the current approach of defining mechanistically based dimensional approaches rather than categorical approaches to psychiatric disorders. The relationship to risk probability and valence may underlie the propensity toward pathological behaviors toward different types of rewards.     

When health means suffering: mammograms,pain and compassionate care

The X‐ray mammogram remains the cornerstone of most public health programmes aimed at the early diagnosis of breast cancer. Its virtues of safety, reliability and cheapness maintain its established position, and Western social and cultural traditions of ambivalence to pain push any questions concerning the painfulness of the procedure into the background. As part of a larger UK/USA‐based empirical study, we undertook a qualitative analysis of women's accounts of pain experienced in mammograms and their reaction to it, comparing their accounts with professional views and advice to patients as reflected in interviews, patient leaflets and practice guidelines. We found considerable variability of experience and reaction to pain among patients, and indications of similar variability in professionals' views and practice, contrasting with a uniformly reassuring message in formal institutional advice. We suggest that in practice professional work‐arounds and patients' felt obligation to tolerate pain bridge this gap, but that action to tackle the problems of dropout and the emotional and operational costs of the current system is nonetheless needed. The need is for concerned groups to combine to establish a serious and sustained programme of amelioration and innovative technological development to assure more compassionate patient care and operational efficiency.     

A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro,in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway

Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum.     

Aneurysms of the ascending aorta and arch: the role of imaging in diagnosis and surgical management

Thoracic aortic aneurysms tend to be asymptomatic and were previously often diagnosed only after a complication such as dissection or rupture occurred. Better imaging techniques and an increase in the use of cross-sectional imaging has led to an increase in the diagnosis of aortic aneurysms, which has allowed for elective treatment prior to the development of a complication. The location, size and etiology of an aneurysm all impact the clinical outcomes and these factors are used to determine the appropriate timing of surgical replacement. Surgeons often rely on the information obtained from preoperative imaging to determine when to intervene and what type of procedure will be necessary, making it important for the radiologist to understand these issues in order to provide the necessary information. Postoperative imaging after surgical replacement of the aorta is also important, as there are some common findings that occur in this patient population that can impact how they are treated. The purpose of this article is to review the etiology and associated findings of aneurysms of the ascending aorta and arch, with a focus on how computed tomography angiography and magnetic resonance angiography findings are used to determine the appropriate timing for elective replacement and the type of surgical procedure, as well as the role of follow-up imaging. This will include a review of the most commonly performed types of surgical procedures, to provide an understanding of how the findings of preoperative imaging studies impact what the surgeon does in the operating room, as well as the expected findings of postoperative imaging studies.     

A strategy for development of computerized critical care decision support systems

It is not enough to merely manage medical information. It is difficult to justify the cost of hospital information systems (HIS) or intensive care unit (ICU) patient data management systems (PDMS) on this basis alone. The real benefit of an integrated HIS or PDMS is in decision support. Although there are a variety of HIS and ICU PDMS systems available there are few that provide ICU decision support. The HELP system at the LDS Hospital is an example of a HIS which provides decision support on many different levels. In the ICU there are decision support tools for antibiotic therapy, nutritional management, and management of mechanical ventilation. Computer protocols for the management of mechanical ventilation (respiratory evaluation, ventilation, oxygenation, weaning and extubation) in patients with adult respiratory distress syndrome ((ARDS) have already been developed and clinically validated at the LDS Hospital. These protocols utilize the bedside intensive care unit (ICU) computer terminal to prompt the clinical care team with therapeutic and diagnostic suggestions. The protocols (in paper flow diagram and computerized form) have been used for over 40,000 hours in more than 125 adult respiratory distress syndrome (ARDS) patients. The protocols controlled care for 94% of the time. The remainder of the time patient care was not protocol controlled was a result of the patient being in states not covered by current protocollogic (e.g. hemodynamic instability, or transport for X-Ray studies). 52 of these ARDS patients met extra corporal membrane oxygenation (ECMO) criteria. The survival of the ECMO criteria ARDS patients was 41%, four times that expected (9%) from historical data (p<0.0002). The success of these computer protocols and their acceptance by the clinical staff clearly establishes the feasibility of controlling the therapy of severely ill patients.Over the last four years we have refined the process which we use for generating computerized protocols. The purpose of this paper is to present the six step development strategy which we are successfully using to produce computerized critical care protocols.