A melt-electrowritten filter for capture and culture of circulating colon cancer cells.

Metastasis is the major cause of death in cancer patients accounting for about 90% of the mortality. The detection and analysis of the hallmark of metastasis, circulating tumor cells (CTCs), have significant impact in cancer biology and clinical practice. However, the scarcity of CTCs in blood, particularly in that of colorectal cancer patients, is a serious bottleneck in the development of CTC-based precision medicine. Herein, the melt electrowriting (MEW) technology was used for reproductive fabrication of a biocompatible antibody-presenting polycaprolactone filter with tailored porous structure. It is demonstrated, for the first time, that such filter can be used not only to catch cancer cells spiked in whole blood but also to culture the cancer cells directly on site. Specifically, HT29 colon cancer cells can be captured with an efficiency of 85%, and when spiked into 4 mL of whole blood, 47% were captured on one Ø12mm filter. Furthermore, repeated capture and culture experiments have shown that as few as 20 HT29 colon cancer cells spiked into 4 mL of whole blood can be captured on the filter and within 2 weeks be expanded on site to become tumor bodies that are visible to the untrained eye. This filter allows for downstream analysis, such as flow cytometry, immunocytochemistry, Western blotting, and rt-qPCR. This technology represents a simple and cost-effective platform that potentially enables fast and efficient culture of rare CTCs from patients' blood. This provides non-invasive alternatives for solid biopsy tumor materials for treatment screening, with great potential to realize precision medicine for cancer treatment.

Is diet associated with physical capacity and fatigue in persons with multiple sclerosis? -Results from a pilot study.

BACKGROUND: Diet may have immunomodulatory effects in persons with multiple sclerosis (PwMS) and studies suggest that diet may be considered a complementary treatment to control the progression of the disease. The role of nutrition in MS and related symptoms have been reported by several studies but remains controversial. OBJECTIVE: To explore the association between dietary intake and physical capacity and fatigue in PwMS. METHODS: An explorative cross-sectional pilot study was conducted, in which 23 ambulatory PwMS were enrolled. Dietary intake was assessed using a 4-day food record. Outcome variables included a 6-Minute Walk Test (6MWT), a VO2max test, and self-reported questionnaires assessing fatigue severity (Fatigue Severity Scale, FSS) and impact (Modified Fatigue Impact Scale, MFIS). Associations between variables were determined using simple and multiple regression analyses. RESULTS: In the simple but not the multiple (adjusted for sex and age) regression analyses the carbohydrate intake (% of total energy intake) was positively associated with physical capacity (i.e. the 6MWT and VO2max test), whereas fat intake (% of total energy intake) was inversely associated with physical capacity. In the multiple regression analyses the absolute intake of ω-3 and vitamin D showed trends towards a positive association with the MFIS physical subscale and VO2max, respectively. CONCLUSION: Although not consistent across analyses, these findings suggest that better physical capacity most often is associated with a diet rich in carbohydrates and reduced fat content. Further research and randomized controlled trials are required to fully assess the role and the efficacy of diet quality and content on physical capacity in PwMS.

Plasma brain-derived neurotrophic factor (BDNF) and sphingosine-1-phosphat (S1P) are NOT the main mediators of neuroprotection induced by resistance training in persons with multiple sclerosis-A randomized controlled trial.

Resistance training (RT) has been shown to elicit neuroprotective effects in persons with multiple sclerosis (pwMS). Brain-derived neurotrophic factor (BDNF) and Sphingosine-1-phosphat (S1P) have been put forward as potent mediators of the neuroprotective effects induced by RT. However, while increases have been shown in acute and chronic circulating BDNF levels in pwMS following aerobic exercise alone or in combination with other exercise regimes, no studies have examined this in response to RT. As a novel 'proof-of-concept' approach, we therefore examined the effects of 24 weeks of RT on acute and chronic circulating BDNF and S1P levels in the same pwMS whom our group had previously observed RT-induced neuroprotective effects in (i.e. increased cortical thickness and preservation of whole brain volume). A total of n = 30 relapsing-remitting pwMS were randomized into a training group (TG: 24 weeks of progressive high intensity resistance training, 2 sessions per week; n = 16, age 44[40:51] years, EDSS score 3.0[2.0:3.5] (median[IQR]) or a control group (CG: 24 weeks of habitual lifestyle; n = 14, age 45[37:47] years, EDSS score 3.0[2.5:3.5]). Plasma levels of BDNF and S1P were assessed by ELISA kits before and after the 24-week intervention period. No within- or between group changes were observed in acute or chronic circulating levels of BDNF. A substantial proportion of the participants had S1P levels below the detection limit, yet no within- or between changes were observed in chronic S1P plasma levels in the remaining samples. Thus, the present findings do not support that circulating plasma BDNF or S1P levels are the main mediators of the neuroprotective effects previously reported in the same group of pwMS.

A mortality risk prediction model for older adults with lymph node-positive colon cancer.

Clinicians are less likely to recommend adjuvant chemotherapy for older adults based on their age alone. This study aimed to develop a mortality risk model to assist treatment decision making by identifying patients who are unlikely to live to benefit from chemotherapy. All lymph node-positive colon cancer patients ≥65 years who received surgery in New South Wales, Australia in 2007/2008 were identified using a linked population-based dataset (n = 1550). A model predicting 1-year all-cause mortality was built using multilevel logistic regression. Risk scores derived from model factors were summed for each patient. One-year mortality was 11.5%. The risk model consisted of 14 factors, including comorbidities, hospital admission factors and other markers of frailty or health status. People with a total score of 0, 1 or 2 were considered at low risk (predicted 1-year mortality of 2.9%), those scoring 3 to 8 at medium risk (7.4% mortality) and those scoring 9 or above at high risk (24.7% mortality). The model had good discrimination (area under the receiver operating characteristic curve = 0.788, 95% confidence interval: 0.752-0.825) and calibration (P = 0.46). The risk model accurately predicts mortality for this cohort and could be useful in shifting the emphasis in chemotherapy decision making from chronological age to the identification of those of any age who will benefit.

Assessment of abdominoperineal resection rate as a surrogate marker of hospital quality in rectal cancer surgery.

BACKGROUND: Rates of abdominoperineal resection (APR) have been suggested as a solitary surrogate marker for comparing overall hospital quality in rectal cancer surgery. This study investigated the value of this marker by examining the associations between hospital APR rates and other quality indicators. METHODS: Hospital-level correlations between risk-adjusted APR rates for low rectal cancer and six risk-adjusted outcomes and six care processes were performed (such as 30-day mortality, complications, timely treatment). The ability of APR rates to discriminate between hospitals' performance was examined by means of hospital variance results in multilevel regression models and funnel plots. RESULTS: A linked population-based data set identified 1703 patients diagnosed in 2007 and 2008 who underwent surgery for rectal cancer. Some 15.9 (95 per cent confidence interval (c.i.) 14.2 to 17.6) per cent of these patients had an APR. Among 707 people with low rectal cancer, 38.2 (34.6 to 41.8) per cent underwent APR. Although risk-adjusted hospital rates of APR for low rectal cancer varied by up to 100 per cent, only one hospital (1 per cent) fell outside funnel plot limits and hospital variance in multilevel models was not very large. Lower hospital rates of APR for low rectal cancer did not correlate significantly with better hospital-level outcomes or process measures, except for recording of pathological stage (r = -0.55, P = 0.019). Patients were significantly more likely to undergo APR for low rectal cancer if they attended a non-tertiary metropolitan hospital (adjusted odds ratio 2.14, 95 per cent c.i. 1.11 to 4.15). CONCLUSION: APR rates do not appear to be a useful surrogate marker of overall hospital performance in rectal cancer surgery.