Citations

BACKGROUND A set of common cancer‐related and treatment‐related symptoms has been proposed for quality of care assessment and clinical research. Using data from a large, multicenter, prospective study, the authors assessed the effects of disease site and stage on the percentages of patients rating these proposed symptoms as moderate to severe. METHODS The severity of 13 symptoms proposed to represent “core” oncology symptoms was rated by 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung, regardless of disease stage or phase of care; 2801 patients (90%) repeated the assessment 4 to 5 weeks later. RESULTS At the time of the initial assessment, approximately 33% of the patients reported ≥ 3 symptoms in the moderate‐to‐severe range; 11 of the 13 symptoms were rated as moderate to severe by at least 10% of all patients and 6 were rated as moderate to severe by at least 20% of those receiving active treatment. Fatigue/tiredness was the most severe symptom, followed by disturbed sleep, pain, dry mouth, and numbness/tingling. More patients with lung cancer and patients receiving active treatment reported moderate to severe symptoms. Percentages of symptomatic patients increased by disease stage, less adequate response to therapy, and declining Eastern Cooperative Oncology Group performance status. The percentages of patients reporting moderate to severe symptoms were stable across both assessments. CONCLUSIONS The results of the current study support a core set of moderate to severe symptoms that are common across outpatients with solid tumors, that can guide consideration of progression‐free survival as a trial outcome, and that should be considered in clinical care and in assessments of quality of care and treatment benefit. Cancer 2013;119:4333–4340 . © 2013 American Cancer Society .

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application.

Background: Telemedical physician triage (TPT) is a potential application of telemedicine in the emergency department (ED). We report the technical success, patient satisfaction, and effect on ED throughput metrics (length of stay [LOS] and time to physician evaluation [TPE]) of TPT performed on a mobile platform. Materials and Methods: Patients underwent standard nursing triage with or without TPT. Technical success is reported as raw data. Patient satisfaction is reported as raw data±standard deviation on a 5-point (low-to-high) scale. LOS and TPE are reported as mean±SD [95% CI] values. Statistical analyses of LOS and TPE are via two-sample t test. Results: One hundred six patients were registered during intervention periods, and TPT was completed in 36 (34%). One hundred ninety-six patients were registered during control periods. The technical success rate was 95%. Average patient satisfaction was 4.7 on a 5-point scale. The primary analysis (106 patients) showed no change in LOS (266±101 [244–288] min versus 258±172 [234–282] min) but a trend toward improved TPE with TPT (35±28 [29–41] min versus 42±31 [38–46] min) ( p =0.052). A secondary analysis (36 patients) showed no change in LOS (273±125 [231–316] min versus 258±172 [234–282] min) but improved TPE with TPT (16±15 [11–21] min versus 42±31 [38–46] min) ( p <0.0001). Conclusions: TPT in the ED on a mobile platform was technically successful, well accepted by patients, and associated with a decrease in TPE but not LOS.

New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75),P<0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

OBJECTIVE Identification of patients at high risk for new-onset diabetes after kidney transplantation (NODAT) will facilitate clinical trials for its prevention. RESEARCH DESIGN AND METHODS We previously described a pretransplant predictive risk model for NODAT using seven pretransplant variables (age, planned use of maintenance corticosteroids, prescription for gout medicine, BMI, fasting glucose, fasting triglycerides, and family history of diabetes). We have now applied the initial model to a cohort of 474 transplant recipients from another center for validation. We performed two analyses in the validation cohort. The first was a standard model with variables derived from the original study. The second was a summary score model, in which the sum of dichotomized variables (all the variables dichotomized at clinically relevant cut points) was used to categorize, individuals into low (0–1), intermediate (2, 3), or high (4–7) risk groups. We also conducted a combined database analyses, merging the initial and validation cohorts (n = 792) to obtain better estimates for a prediction equation. RESULTS Although the frequency of several risk factors differed significantly between the two cohorts, the models performed similarly in each cohort. Using the summary score model, incidences of NODAT in low-risk, medium-risk, and high-risk groups in the initial cohort were 12, 29, and 56%, and in the validation cohort incidences were 11, 29, and 51%. CONCLUSIONS A pretransplant model for NODAT, including many type 2 diabetes risk factors, predicted NODAT in the validation cohort.

Abstract Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune tolerance and tumor growth. Defying these expectations, the adoptive transfer of IL-10–expressing T cells to mice with polyposis attenuates microbial-induced inflammation and suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated IL-10 in T cells in APCΔ468 mice and compared the effects of treatment with broad-spectrum antibiotics. We found that T cells and regulatory T cells (Treg) were a major cellular source of IL-10 in both the healthy and polyp-bearing colon. Notably, T cell–specific ablation of IL-10 produced pathologies that were identical to mice with a systemic deficiency in IL-10, in both cases increasing the numbers and growth of colon polyps. Eosinophils were found to densely infiltrate colon polyps, which were enriched similarly for microbiota associated previously with colon cancer. In mice receiving broad-spectrum antibiotics, we observed reductions in microbiota, inflammation, and polyposis. Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs. Cancer Res; 73(19); 5905–13. ©2013 AACR.

Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 −4 was used to determine statistical significance of the associations. Results Two correlated SNPs—rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10 −5 ), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

Hispanics bear a disproportionate burden of diabetes in the United States, yet relations of structural, socio-cultural and behavioral factors linked to diabetes are not fully understood across all of their communities. The current study examines disparities and factors associated with diabetes in adult Hispanics of Mexican-descent (N = 648) participating in a population survey of an underserved rural U.S.-Mexico border community. The overall rate of diabetes prevalence rate in the sample, based on self-report and a glucose testing, was 21%; much higher than rates reported for U.S. adults overall, for all Hispanic adults, or for Mexican American adults specifically. Acculturation markers and social determinants of health indicators were only significantly related to diabetes in models not accounting for age. Older age, greater BMI (>30), greater waist-to-hip ratio as well as lower fruit and vegetable consumption were significantly related to increased likelihood of diabetes when all structural, cultural, behavioral, and biological factors were considered. Models with sets of behavioral factors and biological factors each significantly improved explanation of diabetes relative to prior social ecological theory-guided models. The findings show a critical need for diabetes prevention efforts in this community and suggest that health promotion efforts should particularly focus on increasing fruit and vegetable consumption.

Consensus abstract Background The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Methods Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. Results The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. Conclusion The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.