Relationship between emergency presentation, systemic inflammatory response, and cancer-specific survival in patients undergoing potentially curative surgery for colon cancer

Background Emergency presentation is recognized to be associated with poorer cancer-specific survival following curative resection for colorectal cancer. The present study examined the hypothesis that an enhanced systemic inflammatory response, prior to surgery, might explain the impact of emergency presentation on survival. Methods In all, 188 patients undergoing potentially curative resection for colorectal cancer were studied. Of these, 55 (29%) presented as emergencies. The systemic inflammatory response was assessed using the Glasgow Prognostic Score (mGPS), which is the combination of an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L). Results In the emergency group, tumor stage was greater (P < 0.01), more patients received adjuvant therapy (P < 0.01) more patients had an elevated mGPS (P < 0.01), and more patients died of their disease (P < 0.05). The minimum follow-up was 12 months; the median follow-up of the survivors was 48 months. Emergency presentation was associated with poorer 3-year cancer-specific survival in those patients aged 65 to 74 years (P < 0.01), in both males and females (P < 0.05), in the deprived (P < 0.01), in patients with tumor-node-metastasis (TNM) stage II disease (P < 0.01), in those who received no adjuvant therapy (P < 0.01), and in the mGPS 0 and 1 groups (P < 0.05) groups. On multivariate survival analysis of patients undergoing potentially curative surgery for TNM stage II colon cancer, emergency presentation (P < 0.05) and mGPS (P < 0.05) were independently associated with cancer-specific survival. Conclusions These results suggest that emergency presentation and the presence of systemic inflammatory response prior to surgery are linked and account for poorer cancer-specific survival in patients undergoing potentially curative surgery for colon cancer. Both emergency presentation and an elevated mGPS should be taken into account when assessing the likely outcome of these patients

Guessing probability distributions from small samples

We propose a new method for the calculation of the statistical properties, as e.g. the entropy, of unknown generators of symbolic sequences. The probability distribution $p(k)$ of the elements $k$ of a population can be approximated by the frequencies $f(k)$ of a sample provided the sample is long enough so that each element $k$ occurs many times. Our method yields an approximation if this precondition does not hold. For a given $f(k)$ we recalculate the Zipf--ordered probability distribution by optimization of the parameters of a guessed distribution. We demonstrate that our method yields reliable results.Comment: 10 pages, uuencoded compressed PostScrip

Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines

Nanoparticulate delivery systems represent an area of particular promise for nanoneuromedicines. They possess significant potential for desperately needed therapies designed to combat a range of disorders associated with aging. As such, the field was selected as the focus for the 2014 meeting of the American Society for Nanomedicine. Regenerative, protective, immune modulatory, anti-microbial and anti-inflammatory products, or imaging agents are readily encapsulated in or conjugated to nanoparticles and as such facilitate the delivery of drug payloads to specific action sites across the blood-brain barrier. Diagnostic imaging serves to precisely monitor disease onset and progression while neural stem cell replacement can regenerate damaged tissue through control of stem cell fates. These, taken together, can improve disease burden and limit systemic toxicities. Such enabling technologies serve to protect the nervous system against a broad range of degenerative, traumatic, metabolic, infectious and immune disorders

Sloan Digital Sky Survey Multicolor Observations of GRB010222

The discovery of an optical counterpart to GRB010222 (detected by BeppoSAX; Piro 2001) was announced 4.4 hrs after the burst by Henden (2001a). The Sloan Digital Sky Survey's 0.5m photometric telescope (PT) and 2.5m survey telescope were used to observe the afterglow of GRB010222 starting 4.8 hours after the GRB. The 0.5m PT observed the afterglow in five, 300 sec g' band exposures over the course of half an hour, measuring a temporal decay rate in this short period of F_nu \propto t^{-1.0+/-0.5}. The 2.5m camera imaged the counterpart nearly simultaneously in five filters (u' g' r' i' z'), with r' = 18.74+/-0.02 at 12:10 UT. These multicolor observations, corrected for reddening and the afterglow's temporal decay, are well fit by the power-law F_nu \propto nu^{-0.90+/-0.03} with the exception of the u' band UV flux which is 20% below this slope. We examine possible interpretations of this spectral shape, including source extinction in a star forming region.Comment: 8 pages, 4 figures, accepted for publication in ApJ. Two figures added, minor changes to text in this draft. Related material can be found at: http://sdss.fnal.gov:8000/grb

The Emerging Role of Interleukin 1β (IL-1β) in Cancer Cachexia

Treatment of cancer cachexia remains an unmet need. The host-tumour interface and the resulting sequestration of the pro-inflammatory cytokine Il-1β is critical in cachexia development. Neuroinflammation mediated via IL-1β through the hypothalamic pituitary axis results in increased muscle proteolysis and adipose lipolysis, thus creating a prolonged stress-like environment with loss of appetite and increased resting energy expenditure. Recent trials using a monoclonal antibody targeting IL-1β, canakinumab, have shown a potential role in lung cancer; however, a potential role of targeting IL-1β to treat cachexia in patients with lung cancer is unclear, yet the underlying pathophysiology provides a sound rationale that this may be a viable therapeutic approach

REVOLUTION (Routine EValuatiOn of people LivIng with caNcer)—protocol for a prospective characterisation study of patients with incurable cancer

Introduction: There is a pressing need for a holistic characterisation of people with incurable cancer. In this group, where quality of life and improvement of symptoms are therapeutic priorities, the physical and biochemical manifestations of cancer are often studied separately, giving an incomplete picture. In order to improve care, spur therapeutic innovation, provide meaningful endpoints for trials and set priorities for future research, work must be done to explore how the tumour influences the clinical phenotype. Characterisation of the host-tumour interaction may also provide information regarding prognosis, allowing appropriate planning of investigations, treatment and referral to palliative medicine services. Methods: Routine EValuatiOn of people LivIng with caNcer (REVOLUTION) is a prospective observational study that aims to characterise people with incurable cancer around five key areas, namely body composition, physical activity, systemic inflammatory response, symptoms, and quality of life by developing a bio-repository. Participants will initially be recruited from a single centre in the UK and will have assessments of body composition (bio-impedance analysis [BIA] and computed tomography [CT]), assessment of physical activity using a physical activity monitor, measurement of simple markers of inflammation and plasma cytokine proteins and three symptom and quality of life questionnaires. Discussion: This study aims to create a comprehensive biochemical and clinical characterisation of people with incurable cancer. Data in this study can be used to give a better understanding of the ‘symptom phenotype’ and quality of life determinants, development of a profile of the systemic inflammatory response and a detailed characterisation of body composition

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

Determinants of quality of life in patients with incurable cancer

Optimizing quality of life (QoL) remains the central tenet of care in patients with incurable cancer; however, determinants of QoL are not clear. The objective of the current study was to examine which factors influence QoL in patients with incurable cancer. A multicenter study of adult patients with advanced cancer was conducted in Ireland and the United Kingdom between 2011 and 2016. Data were collected from patients at study entry and included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG-PS), nutritional parameters (the percentage weight loss [%WL]), muscle parameters assessed using computed tomography images (skeletal muscle index and skeletal muscle attenuation), inflammatory markers (modified Glasgow Prognostic score [mGPS]), and QoL data (the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30). The relation between clinical, nutritional, and inflammatory parameters with QoL was assessed using the Spearman rank correlation coefficient and multivariate binary logistic regression. Components of the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30 (physical function, fatigue, and appetite loss) and summary QoL scores were mean-dichotomized for the logistic regression analyses. Data were available for 1027 patients (51% men; median age, 66 years). Gastrointestinal cancer was most prevalent (40%), followed by lung cancer (26%) and breast cancer (9%). Distant metastatic disease was present in 87% of patients. The %WL, ECOG-PS, and mGPS were significantly correlated with deteriorating QoL functional and symptom scales (all P < .001). On multivariate regression analysis, >10% WL (odds ratio [OR], 2.69; 95% CI, 1.63-4.42), an ECOG-PS of 3 or 4 (OR, 14.33; 95% CI, 6.76-30.37), and an mGPS of 2 (OR, 1.58; 95% CI, 1.09-2.29) were independently associated with poorer summary QoL scores. These parameters were also independently associated with poorer physical function, fatigue, and appetite loss (all P < .05). Low skeletal muscle attenuation was independently associated with poorer physical functioning (OR, 1.67; 95% CI, 1.09-2.56), but muscle parameters were not independently associated with fatigue, appetite loss, or QoL summary scores. The current findings indicate that QoL is determined (at least in part) by WL, ECOG-PS, and the systemic inflammatory response in patients with advanced cancer. Identifying early predictors of poor QoL may allow the identification of patients who may benefit from early referral to palliative and supportive care, which has been shown to improve QoL