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Accelerated functional decline is a concern among older cancer survivors that threatens independence and quality of life. Pilot studies suggest that vegetable gardening interventions ameliorate functional decline through improved diet and physical activity.The aim of this article was to describe the rationale, recruitment challenges, and enrollment for the Harvest for Health randomized controlled trial (RCT), which will test the impact of a home-based, vegetable gardening intervention on vegetable and fruit consumption, physical activity, and physical functioning among older cancer survivors. Modifications made to the intervention and assessments to assure safety and continuity of the RCT throughout the COVID-19 pandemic also are reported.Harvest for Health is a 2-year, 2-arm, single-blinded, wait-list controlled RCT with cross-over.Medicare-eligible survivors of cancers with ≥60% 5-year survival were recruited across Alabama from October 1, 2016 to February 8, 2021.Participants were randomly assigned to a wait-list control or a 1-year home-based gardening intervention and individually mentored by extension-certified master gardeners to cultivate spring, summer, and fall vegetable gardens.Although the RCT's primary end point was a composite measure of vegetable and fruit consumption, physical activity, and physical functioning, this article focuses on recruitment and modifications made to the intervention and assessments during COVID-19.χOlder cancer survivors (n = 9,708) were contacted via mail and telephone; 1,460 indicated interest (15% response rate), 473 were screened eligible and consented, and 381 completed baseline assessments and were randomized. Enrollees did not differ from nonrespondents/refusals by race and ethnicity, or rural-urban status, but comprised significantly higher numbers of comparatively younger survivors, those who were female, and survivors of breast cancer (P.001). Although COVID-19 delayed trial completion, protocol modifications overcame this barrier and study completion is anticipated by June 2022.This RCT will provide evidence on the effects of a mentored vegetable gardening program among older cancer survivors. If efficacious, Harvest for Health represents a novel, multifaceted approach to improve lifestyle behaviors and health outcomes among cancer survivors-one with capacity for sustainability and widespread dissemination.

Background The number of exercise trials examining cardiometabolic outcomes in spinal cord injury (SCI) is low, and prescribed exercise is often inconvenient for individuals with SCI to perform within their community. Individuals with SCI experience a myriad of barriers to exercise participation, which can include a lack of time, accessible or usable equipment and facilities, and transportation. Thus, it is imperative to identify effective modes of exercise that provide the greatest overall health benefits but do not require a significant time commitment. Low-volume high intensity interval training (HIIT) has demonstrated the same improvements in cardiometabolic health as moderate intensity exercise training (MIT), despite only requiring 20% of the total time commitment in adults without disabilities and more recently in individuals with SCI. Objectives The primary purpose of this study is to integrate a 16 week home-based telehealth HIIT arm crank exercise training program in individuals with SCI and assess changes in cardiometabolic health. Methods Men and women between the ages of 19 and 60 with a confirmed diagnosis of SCI between C7 and T12 will be recruited for this study. Participants will be randomized to 16 weeks of telehealth HIIT exercise two days per week or a no-exercise control group. Aerobic capacity, muscular strength, blood lipids, glucose tolerance, resting energy expenditure, blood pressure, and body composition will be assessed at baseline and 16 weeks post-training. Discussion Inactivity associated with SCI leads to chronic cardiometabolic health conditions. The majority of exercise interventions to date show that exercise is capable of increasing physical function, aerobic capacity, and muscle mass, and strength. Additionally, we have recently shown the ability of HIIT to improve blood lipid and glucose concentrations. Advances in telehealth exercise approaches have improved the capability to prescribe home-based exercise programs. Therefore, we hypothesize that the utilization of a home-based telehealth HIIT program will improve cardiometabolic health markers, yield high adherence (> 75%), and will be more enjoyable in individuals with SCI. Trial registration Telehealth High-Intensity Interval Exercise and Cardiometabolic Health in Spinal Cord Injury NCT04940598

PURPOSE: To qualitatively explore exercise barriers and facilitators experienced by rural female cancer survivors from the program interventionist and recipient perspective for the purpose of enhancing exercise program implementation and uptake in rural settings. METHODS: A descriptive qualitative study design was utilized. Focus groups were conducted prior to implementation of an evidence-based exercise program by a rural non-research cancer clinical site. Nineteen rural female cancer survivors (mean age = 61.7 ± 10.9 years) and 11 potential interventionists (mean age = 42.3 ± 15.3 years) completed focus groups (stratified by participant role). Focus groups were audio recorded, transcribed, coded, and analyzed using inductive thematic analysis with NVivo 11. RESULTS: Cancer survivors identified twelve barrier themes (cancer specific adverse effects, lack of support, lack of knowledge, perceived negative aspects of exercise, cost, lack of resources, motivation, inconvenience, lack of program flexibility, time, weather, safety) and eight facilitator themes (knowledge, ease of access, resources, awareness, cost, options, organized, fun) related to exercise. Interventionists identified seven barrier themes (cost, transportation, lack of cancer survivor and interventionist knowledge, fear, motivation, lack of support, lack of resources) and four facilitator themes (resources, support, knowledge, motivation). Narratives revealed differing role-specific perspectives on shared themes between survivors and interventionists as well as potential implementation strategies for enhancing exercise participation and exercise program uptake among rural female cancer survivors. CONCLUSION: Exploring multi-level stakeholder perspectives on cancer survivors’ exercise needs and related strategies yields important information for organizations to consider when implementing exercise programs in rural contexts.

Obesity adversely impacts overall and cancer‐specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, feasibility and effects in patients are unknown. A two‐arm, single‐blinded, randomized controlled weight‐loss trial was undertaken presurgery among 32 overweight/obese, Stage 0–II breast cancer patients. The attention control arm (AC) received basic nutritional counseling and upper‐body progressive resistance training whereas the weight loss intervention (WLI) arm received identical guidance, plus counseling on caloric restriction and aerobic exercise to promote 0.68–0.92 kg/week weight loss. Anthropometrics, body composition, blood and survey data were collected at baseline and presurgery ∼30 days later. Tumor markers (e.g., Ki67) and gene expression were assessed on biopsy and surgical specimens; sera were analyzed for cytokines, growth and metabolic factors. Significant WLI vs. AC differences were seen in baseline‐to‐follow‐up changes in weight (−3.62 vs. −0.52 kg), %body fat (−1.3 vs. 0%), moderate‐to‐vigorous physical activity (+224 vs. +115 min/week), caloric density (−0.3 vs. 0 kcal/g), serum leptin (−12.3 vs. −4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle‐apoptosis related genes (CC‐ARG; all p‐values, What's new? Obesity adversely impacts survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, effects in patients are unknown. This is the first randomized controlled trial to assess the impact of a pre‐surgical weight loss intervention among early‐stage breast cancer patients. Results show the effects of acute negative energy balance on tumor biology, circulating biomarkers, and quality‐of‐life. Short‐term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to pre‐surgical caloric restriction. Such interventions may be better timed after surgical resection, though cell cycle‐apoptosis and DNA damage‐repair scores support increasing physical activity.

To evaluate the adherence and effectiveness of a home-based exergame program for patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF were randomly assigned to a relatively unsupervised Wii Fit exergame intervention group or Wii video game control group (with no active whole-body movement involved). Participants in both groups were instructed to play their respective games 30 min/d, 3 d/wk for 12 wk. In addition, they were asked to perform their usual exercise/physical activities. Outcome measures were 6-min walk distance (6MWD), exercise-related dyspnea, and St George's Respiratory Questionnaire (SGRQ).The 20 participants differed significantly between intervention and control groups in baseline characteristics (forced vital capacity = 2.0 ± 0.5 vs 3.1 ± 0.7 L; forced expiratory volume in 1 sec = 1.7 ± 0.4 vs 2.5 ± 0.6 L, respectively). Participant adherence rate to the exergame program was very low (20%). There was no significant improvement in the outcome measures in either group. In fact, both the intervention and control groups had a deterioration in 6MWD (-22 ± 56 m vs -60 ± 111 m), respectively and SGRQ scores (3 ± 9 vs 1 ± 11), respectively.The home-based exergame intervention for patients with IPF did not show improvement in functional performance, dyspnea, or health-related quality of life at the completion of the 12-wk program in our 2 heterogeneous groups. In addition to the low adherence rate, insufficient frequencies and durations of exergaming may contribute to the lack of improvement. A lack of effectiveness of home-based pulmonary rehabilitation using exergaming for patients with IPF appears consistent with prior observational studies that used more traditional modes of home-based exercise.

Background: Metabolic disorders (e.g., impaired glucose tolerance, insulin resistance, and type 2 diabetes) are more prevalent in people with spinal cord injury (SCI) vs. able-bodied individuals. Dietary modification is a more cost-effective treatment option than pharmacological therapies for reducing the risk of metabolic dysfunction. Lowering carbohydrate, increasing protein, and maintaining a proper dietary fat intake are expected to induce favorable adaptations in glucose control, body fat distribution, and the composition of gut microbiome. However, dietary modification has not been rigorously investigated in people with SCI. The purpose of this study is to determine if an 8-week low-carbohydrate/high-protein (LC/HP) dietary intervention will show improvements in clinically important metrics of metabolic function, body composition, the composition of gut bacteria, and quality of life. Methods: We intend to recruit 100 participants with chronic traumatic SCI (3 years post-injury, C5-L2, AIS A-D, and 18-65 yr) and insulin resistance, impaired glucose tolerance or untreated type 2 diabetes and randomly assign them into an 8-week LC/HP dietary intervention group or a control group. The daily LC/HP dietary intervention includes ~30% total energy as protein (1.6 g/kg per day) with a carbohydrate-to-protein ratio Discussion: New and impactful information to be derived from this project will result in the development of a low-cost, simple, self-administered LC/HP dietary intervention for improving metabolic function in individuals with chronic SCI, improved understanding of the composition of gut bacteria in SCI, and how an LC/HP dietary intervention alters gut bacteria composition. In addition, this project will improve our understanding of the relationship between metabolic function and quality of life in individuals with long-standing SCI. Trial Registration: ClinicalTrials.gov, NCT03207841. Registered 5 June 2017, https://clinicaltrials.gov/ct2/show/NCT03207841. Keywords: Spinal cord injury, high-protein diet, low-carbohydrate diet, metabolic disease, insulin sensitivity, diabetes, gut microbiome.

To identify constructs relevant to implementation of evidence-based physical activity (PA) behavior change interventions for rural women cancer survivors from an organizational perspective. During the development of a PA intervention implementation toolkit, 11 potential interventionists and 19 community and organizational stakeholders completed focus groups stratified by role. Narratives were audio recorded, transcribed, and coded for Consolidated Framework for Implementation Research (CFIR) constructs. Multiple CFIR constructs were identified: Implementation Process (i.e., Engaging, Reflecting and Evaluating), Intervention Characteristics (i.e., Design Quality and Packaging, Cost, Evidence Strength and Quality, Adaptability, Complexity), Inner Setting (i.e., Implementation Readiness, Implementation Climate, Structural Characteristics), Outer Setting (i.e., Patient Needs and Resources, Cosmopolitanism), and Characteristics of Individuals (i.e., Knowledge and Beliefs, Stage of Change). Narratives identified rural implementation barriers (e.g., transportation) and facilitators (e.g., community-oriented). Unique needs of the cancer survivor (e.g., coping during cancer treatment and long-term effects on physical abilities) were emphasized as important barriers potentially addressed through Adaptability and Readiness implementation strategies. Narratives identified multi-level (i.e., individual-, organizational-, and community-level) strategies for targeting the identified constructs. Fourteen CFIR constructs emerged as potentially important for organizations to consider when implementing PA interventions. Constructs were integrated into our implementation toolkit and research testing their potential mechanisms of action when implementing PA interventions in rural settings is warranted. Strategies that target the identified constructs may enhance the implementation of PA programs for rural cancer survivors. Cancer survivors can facilitate these efforts by partnering with their health care providers and community organizations. Organizations promoting physical activity programs for cancer survivors must overcome implementation barriers including but not limited to cost, necessary expertise, and lack of awareness. Cancer survivors can facilitate these efforts by partnering with their health care providers, cancer center, and local community organizations to raise awareness and champion these efforts. It will “take a village”, with cancer survivors being their own best advocate, to bring physical activity promotion to a broad range of cancer survivors.

This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.8 ± 6.3 yr postinjury; 6 Comb-Ex and 5 HP diet) completed the study. Comb-Ex training occurred 3 days/wk and consisted of upper body resistance training (RT) in addition to neuromuscular electrical stimulation (NMES)-induced-RT for paralytic VL muscle. Strength training was combined with high-intensity arm-cranking exercises (1-min intervals at 85–90%, V̇o2peak) for improving cardiovascular endurance. For the HP diet intervention, protein and fat each comprised 30%, and carbohydrate comprised 40% of total energy. Clinical tests and muscle biopsies were performed 24 h before and after the last exercise or diet session. The Comb-Ex intervention increased Type IIa myofiber distribution and CSA in VL muscle and Type I and IIa myofiber CSA in deltoid muscle. In addition, Comb-Ex increased lean thigh mass, V̇o2peak, and upper body strength ( P < 0.05). These results suggest that exercise training is required to promote favorable changes in paralytic and nonparalytic muscles in individuals with long-standing SCI, and adequate dietary protein consumption alone may not be sufficient to ameliorate debilitating effects of paralysis. NEW & NOTEWORTHY This study is the first to directly compare the effects of an isocaloric high-protein diet and combination exercise training on clinical and molecular changes in paralytic and nonparalytic muscles of individuals with long-standing spinal cord injury. Our results demonstrated that muscle growth and fiber-type alterations can best be achieved when the paralyzed muscle is sufficiently loaded via neuromuscular electrical stimulation-induced resistance training.

Summary Introduction The incidence of pediatric urolithiasis has been increasing over the years; however, the etiology of this increase is not well understood. Age, body mass index, and gender have been examined as possible risk factors for stone disease, but with inconsistent and variable associations. Objective We aim to investigate the urine chemistry factors, as assessed by 24-h urinary parameters, in pediatric stone formers at a large volume tertiary referral center in the highest areas in the United States, the Southeast, based on age, body mass index, and gender. Study design We retrospectively reviewed all pediatric stone formers who completed a 24-h study between 2005 and 2016. Patients were stratified by age (3–10 versus 11–18 years of age), overweight status (above versus below the 85th percentile for body mass index), and gender (male versus female) (Summary Figure). Statistical analysis included analysis of variance and logistic regression. Results 243 patients were included in our analysis. Patients in the first decade of life were found to have greater numbers of urinary risk factors than those in the second decade. Non-overweight patients were more likely to have hyperoxaluria and hyperuricosuria, while overweight patients were more likely to have hypocitraturia. Female patients were more likely to have higher hyperoxaluria, while male patients were more likely to have hypercalciuria. Discussion In contrast to prior publications, obesity is not linked to increased risk of urolithiasis with non-overweight individuals having a greater number of risk factors than the overweight cohort. Despite stone disease being more prevalent in adolescents, the greatest number of risk factors were present in the first decade of life. Lastly, female children had more urinary risk factors than males. Further understanding of the underlying causes of stone disease in various pediatric populations is warranted. Conclusion While more urinary risk factors were identified in younger, non-overweight, and female patients, there remains no consensus on the urinary risk factors for pediatric urolithiasis. Further study is needed to elucidate the risk factors and pathophysiology of pediatric stone disease.

We evaluated the role of lymph node (LN) retrieval in pancreatic adenocarcinoma (PA) patients undergoing pancreaticoduodenectomy (PD).We utilized the National Cancer Data Base; Cox regression models and logistic regression models were used for statistical evaluation.We evaluated 26,792 patients with PA who underwent PD. The mean LN retrieved in LN(-) patients was 10.8 vs 14.4 for LN(+) patients (P 0.0001). Greater LN retrieval is an independent predictor of a negative microscopic margin and decreased length of stay. The median survival of LN(-) patients exceeded that of LN(+) patients (24.5 vs 15.1 months, P 0.0001). Increasing LN retrieval is a significant predictor of survival in all patients, and in LN(-) patients. The relationship of increased LN retrieval and enhanced survival is a nearly linear trend.Rather than demonstrating an inflection point that defines the extent of adequate lymphadenectomy, this dataset demonstrates an incremental relationship between LN retrieval and survival.

To examine the association of age when adult height was attained with glioma risk. We analyzed data from a US-based case–control study of glioma risk factors. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated between age at attainment of adult height and glioma risk. Multivariate models were adjusted for age, race, sex, education, and state of residence. We examined associations overall, and according to glioma grade, sex, and final adult height. The study set included n = 951 controls and n = 776 cases, with a median age of 56 (18–92); the majority was male (53.8%) and identified as Caucasian. Older age at height completion was associated with an increased risk of glioma. A significant positive trend was observed both for glioblastoma (OR 1.10; 95% CI 1.04–1.17 per 1-year increase in age) and lower grade non-glioblastoma subtypes combined (OR 1.18; 95% CI 1.10–1.28 per year increase in age). The association was observed in men and women, and in all categories of final adult height. We observed for the first time a positive association between glioma risk and a prolonged adolescent growth phase. Our results suggest a role for factors governing the timing and intensity of growth in adolescence as risk-determining exposures in adult glioma.

BACKGROUND. Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset of individuals with COPD with an inflammatory phenotype who are at increased risk for acute exacerbation (AECOPD). METHODS. We analyzed Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene) cohorts for which baseline and prospective data were available. Elevated MMP-9 was defined based on >95th percentile plasma values from control (non-COPD) sample in SPIROMICS. COPD subjects were classified as having elevated or nonelevated MMP-9. Logistic, Poisson, and Kaplan-Meier analyses were used to identify associations with prospective AECOPD in both cohorts. RESULTS. Elevated MMP-9 was present in 95/1,053 (9%) of SPIROMICS and 41/140 (29%) of COPDGene participants with COPD. COPD subjects with elevated MMP-9 had a 13%–16% increased absolute risk for AECOPD and a higher median (interquartile range; IQR) annual AECOPD rate (0.33 [0–0.74] versus 0 [0–0.80] events/year and 0.9 [0.5–2] versus 0.5 [0–1.4] events/year for SPIROMICS and COPDGene, respectively). In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95%CI, 1.00–2.90; and OR, 3.03; 95%CI, 1.02–9.01), frequency (incidence rate ratio [IRR], 1.45; 95%CI, 1.23–1.7; and IRR, 1.24; 95%CI, 1.03–1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively. CONCLUSIONS. Elevated MMP-9 was independently associated with AECOPD risk in 2 well-characterized COPD cohorts. These findings provide evidence for MMP-9 as a prognostic biomarker and potential therapeutic target in COPD. TRIAL REGISTRATION. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01969344","term_id":"NCT01969344"}}NCT01969344 (SPIROMICS) and {"type":"clinical-trial","attrs":{"text":"NCT00608764","term_id":"NCT00608764"}}NCT00608764 (COPDGene). FUNDING. This work was funded by K08 HL123940 to JMW; R01HL124233 to PJC; Merit Review I01 {"type":"entrez-nucleotide","attrs":{"text":"CX000911","term_id":"56272327","term_text":"CX000911"}}CX000911 to JLC; R01 (R01HL102371, R01HL126596) and VA Merit (I01BX001756) to AG. SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) is funded by contracts from the NHLBI (HHSN268200900013C, HHSN268200900014C,HHSN268200900015C HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, and HHSN268200900020C) and a grant from the NIH/NHLBI (U01 {"type":"entrez-nucleotide","attrs":{"text":"HL137880","term_id":"1051916464","term_text":"HL137880"}}HL137880), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals Inc.; Chiesi Farmaceutici; Forest Research Institute Inc.; GlaxoSmithKline; Grifols Therapeutics Inc.; Ikaria Inc.; Novartis Pharmaceuticals Corporation; Nycomed GmbH; ProterixBio; Regeneron Pharmaceuticals Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan. COPDGene is funded by the NHLBI (R01 HL089897 and R01 HL089856) and by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

Background Thousands of neurosurgical emergencies are transferred yearly to tertiary care facilities to assume a higher level of care. Several studies have examined how neurosurgical transfers influence patient outcomes, but characteristics of potentially avoidable transfers have yet to be investigated. Objective To identify whether potentially avoidable transfers represent a significant portion of transfers to a tertiary neurosurgical facility. Methods In this cohort study, we evaluated 916 neurosurgical patients transferred to a tertiary care facility over a 2-year period. Transfers were classified as potentially avoidable when no neurosurgical diagnostic test, intervention, or intensive monitoring was deemed necessary (n = 180). The remaining transfers were classified as justifiable (n = 736). The main outcomes and measures were age, sex, diagnosis, insurance status, intervention, distance of transfer, length of hospital and intensive care unit stay, mortality, discharge disposition, and cost. Results Nearly 20% of transfers were identified as being potentially avoidable. Although some of these patients had suffered devastating, irrecoverable neurological insults, many had innocuous conditions that did not require transfer to a higher level of care. Justifiable transfers tend to involve patients with nontraumatic intracranial hemorrhage and cranial neoplasm. Both groups were admitted to the intensive care unit at the same rate (approximately 70% of patients). Finally, the direct transportation cost of potentially avoidable transfers was $1.46 million over 2 years. Conclusion This study identified the frequency and expense of potentially avoidable transfers. There is a need for closer examination of the clinical and financial implications of potentially avoidable transfers. Abbreviations CI, confidence intervalIQR, interquartile rangeJT, justifiable transferOR, odds ratioPAT, potentially avoidable transferUAB, University of Alabama at Birmingham.

OBJECT Handoffs and services changes are potentially modifiable sources of medical error and delays in transition of care. This cohort study assessed the relationship between resident service handoffs and length of stay for neurosurgical patients. METHODS All patients admitted to the University of Alabama at Birmingham neurosurgical service between July 1, 2012, and July 1, 2014, were retrospectively identified. A service handoff was defined as any point when a resident handed off coverage of a service for longer than 1 weekend. A conditional probability distribution was constructed to adjust length of stay for the increasing probability of a random handoff. The Student t-test and ANCOVA were used to assess relationships between resident service handoffs and length of hospital stay, adjusted for potential confounders. RESULTS A total of 3038 patients met eligibility criteria and were included in the statistical analyses. Adjusted length of hospital stay (5.32 vs 3.53 adjusted days) and length of ICU stay (4.38 vs 2.96 adjusted days) were both longer for patients who experienced a service handoff, with no difference in mortality. In the ANCOVA model, resident service handoff remained predictive of both length of hospital stay (p < 0.001) and length of ICU stay (p < 0.001). CONCLUSIONS Occurrence of a resident service handoff is an independent predictor of length of hospital and ICU stay in neurosurgical patients. This finding is novel in the neurosurgical literature. Future research might identify mechanisms for improving continuity of care and mitigating the effect of resident handoffs on patient outcomes.

Background Subdural hematoma (SDH) in the elderly is an increasingly common entity because of increased use of antithrombotic medications, an aging population, and increasing frequency of geriatric trauma. The present study describes the functional outcomes and mortality of SDH in an elderly population and to identify potential prognostic factors. Methods Patients >65 years of age with SDH who were treated at our institution from 2005 to 2015 were identified. Patients with a history of preceding high-velocity trauma were excluded. Electronic medical records were retrospectively reviewed. The outcomes of interest were mortality, length of stay, and discharge Glasgow Outcome Score. Results A total of 671 patients were included in final statistical analyses. For patients with acute SDH, survival was 74.9%, 72.3%, and 69.8% at 30, 60, and 100 days, respectively. With respect to chronic SDH, survival was 87.0%, 83.7%, and 80.3% at 30, 60, and 100 days, respectively. On multivariate analysis, admission Glasgow Coma Scale (GCS) score was significantly predictive of mortality in both the acute and chronic populations. In the acute cohort, admission GCS score was a significant predictor of increased length of stay, whereas age >80 years, admission GCS score, contusion volume >10 cm3, SDH volume >50 cm3, and antiplatelet use were significant predictors of discharge functional status. Conclusions SDH in the elderly carries high morbidity and mortality and several prognostic factors were identified. These results can be used to guide discussions with family regarding prognosis and perhaps aid in treatment decisions.

Lung cancer is the leading cause of cancer related deaths. Common molecular drivers of lung cancer are mutations in receptor tyrosine kinases (RTKs) leading to activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pro-growth, pro-survival signaling pathways. Myristoylated alanine rich C-kinase substrate (MARCKS) is a protein that has the ability to mitigate this signaling cascade by sequestering the target of PI3K, phosphatidylinositol (4,5)-bisphosphate (PIP2). As such, MARCKS has been implicated as a tumor suppressor, though there is some evidence that MARCKS may be tumor promoting in certain cancer types. Since the MARCKS function depends on its phosphorylation status, which impacts its subcellular location, MARCKS role in cancer may depend highly on the signaling context. Currently, the importance of MARCKS in lung cancer biology is limited. Thus, we investigated MARCKS in both clinical specimens and cell culture models. Immunohistochemistry scoring of MARCKS protein expression in a diverse lung tumor tissue array revealed that the majority of squamous cell carcinomas stained positive for MARCKS while other histologies, such as adenocarcinomas, had lower levels. To study the importance of MARCKS in lung cancer biology, we used inducible overexpression of wild-type (WT) and non-phosphorylatable (NP)-MARCKS in A549 lung cancer cells that had a low level of endogenous MARCKS. We found that NP-MARCKS expression, but not WT-MARCKS, enhanced the radiosensitivity of A549 cells in part by inhibiting DNA repair as evidenced by prolonged radiation-induced DNA double strand breaks. We confirmed the importance of MARCKS phosphorylation status by treating several lung cancer cell lines with a peptide mimetic of the phosphorylation domain, the effector domain (ED), which effectively attenuated cell growth as measured by cell index. Thus, the MARCKS ED appears to be an important target for lung cancer therapeutic development.

Data from large randomized controlled trials confirming sleep quality improvements with aerobic physical activity have heretofore been lacking for post-primary treatment breast cancer survivors. Our primary purpose for this report was to determine the effects of a physical activity behavior change intervention, previously reported to significantly increase physical activity behavior, on sleep quality in post-primary treatment breast cancer survivors.Post-primary treatment breast cancer survivors (n = 222) were randomized to a 3-month physical activity behavior change intervention (Better Exercise Adherence after Treatment for Cancer [BEAT Cancer]) or usual care. Self-report (Pittsburgh Sleep Quality Index [PSQI]) and actigraphy (latency and efficiency) sleep outcomes were measured at baseline, 3 months (M3), and 6 months (M6).After adjusting for covariates, BEAT Cancer significantly improved PSQI global sleep quality when compared with usual care at M3 (mean between-group difference [M] = -1.4, 95% confidence interval [CI] = -2.1 to -0.7, P0.001) and M6 (M = -1.0, 95% CI = -1.7 to -0.2, P = 0.01). BEAT Cancer improved several PSQI subscales at M3 (sleep quality M = -0.3, 95% CI = -0.4 to -0.1, P = 0.002; sleep disturbances M = -0.2, 95% CI = -0.3 to -0.03, P = 0.016; daytime dysfunction M = -0.2, 95% CI = -0.4 to -0.02, P = 0.027) but not M6. A nonsignificant increase in percent of participants classified as good sleepers occurred. No significant between-group difference was noted for accelerometer latency or efficiency.A physical activity intervention significantly reduced perceived global sleep dysfunction at 3 and 6 months, primarily because of improvements in sleep quality aspects not detected with accelerometer.

The purpose of this study was to assess the feasibility, acceptability, and impact of a ballroom dance intervention on improving quality of life (QOL) and relationship outcomes in cancer survivors and their partners. We conducted a pilot randomized controlled trial with two arms (Restoring Health in You (and Your Partner) through Movement, RHYTHM): (1) immediate dance intervention and (2) delayed intervention (wait-list control). The intervention consisted of 10 private weekly dance lessons and 2 practice parties over 12 weeks. Main outcomes were physical activity (Godin Leisure-Time Exercise Questionnaire), functional capacity (6 Minute Walk Test), QOL (SF-36), Couples’ trust (Dyadic Trust Scale), and other dyadic outcomes. Exit interviews were completed by all participating couples. Thirty-one women survivors (68% breast cancer) and their partners participated. Survivors were 57.9 years old on average and 22.6% African American. Partners had similar characteristics. RHYTHM had significant positive effects on physical activity (p = 0.05), on the mental component of QOL (p = 0.04), on vitality (p = 0.03), and on the dyadic trust scale (p = 0.04). Couples expressed satisfaction with the intervention including appreciating the opportunity to spend time and exercise together. Survivors saw this light-intensity physical activity as easing them into becoming more physically active. Light intensity ballroom dancing has the potential to improve cancer survivors’ QOL. Larger trials are needed to build strong support for this ubiquitous and acceptable activity. Ballroom dance may be an important tool for cancer survivors to return to a physically active life and improve QOL and other aspects of their intimate life.

The American Cancer Society is a leader in the development of cancer survivorship resources. One resource of the American Cancer Society is the I Can Cope program, an educational program for cancer survivors and their families. Evaluations of this program indicate that cancer patients highly rate its objectives. Yet, there are gaps in the understanding of the full impact of the program on diverse cancer survivors. In this study, the authors used a randomized trial to evaluate the program. Participants included 140 low-income survivors (79% Black; 38% breast cancer) from community hospitals who were randomized to 4 sessions of I Can Cope (learning about cancer; understanding cancer treatments; relieving cancer pain; and keeping well in mind and body) or 4 sessions of a wellness intervention (humor, meditation, relaxation, and music therapy). The authors’ primary outcome was “met information needs.” After controlling for covariates, their analysis indicated that I Can Cope was no more effective than the wellness intervention in addressing survivor information needs relative to the learning objectives. Participants provided high overall ratings for both interventions. Self-efficacy for obtaining advice about cancer, age, education, and income were associated with information needs. Educational programs tailored to levels of self-efficacy and patient demographics may be needed.

The aim of this study was to determine the issues patients worry about when making decisions about cancer treatment. A total of 5,044 colorectal and lung cancer patients from the Cancer Care Outcomes Research and Surveillance Consortium reported their level of worry about (1) treatment side effects, (2) treatment costs, (3) time away from family, (4) time away from work, and (5) transportation to treatment sites. Using multivariable logistic regression, we evaluated the association of sociodemographic, clinical, and psychosocial variables with worry. Overall, 75 % of patients worried about side effects of treatments; 40 %, the cost of treatment; 50 %, time away from family; 52 %, time away from work; and 22 %, about transportation. In multivariable analyses, across all worry domains, older patients had lower odds of reporting worry (p values

In May 2005, the Lung Allocation Score (LAS) became the primary method for determining allocation of lungs for organ transplantation for those at least 12 years of age in the United States. During the pre-LAS period, black patients were more likely than white patients to become too sick or die while awaiting transplant. The association between gender and lung transplant outcomes has not been widely studied.Black and white patients aged ≥ 18 years registered on the United Network for Organ Sharing (UNOS) lung transplantation waiting list from January 1, 2000, to May 3, 2005 (pre-LAS, n = 8,765), and from May 4, 2005, to September 4, 2010 (LAS, n = 8,806), were included. Logistic regression analyses were based on smaller cohorts derived from patients listed in the first 2 years of each era (2,350 pre-LAS, and 2,446 LAS) to allow for follow-up time. Lung transplantation was the primary outcome measure. Multivariable analyses were performed within each interval to determine the odds that a patient would die or receive a lung transplant within 3 years of listing.In the pre-LAS era, black patients were more likely than white patients to become too sick for transplantation or die within 3 years of waiting list registration (43.8% vs 30.8%; odds ratio [OR], 1.84; p0.001). Race was not associated with death or becoming too sick while listed for transplantation in the LAS era (14.0% vs 13.3%; OR, 0.93; p = 0.74). Black patients were less likely to undergo transplantation in the pre-LAS era (56.3% vs 69.2%; OR, 0.54; p0.001) but not in the LAS era (86.0% vs 86.7%; OR, 1.07; p = 0.74). Women were more likely than men to die or become too sick for transplantation within 3 years of listing in the LAS era (16.1% vs 11.3%; OR, 1.58; p0.001) compared with the pre-LAS era (33.4% vs 30.7%; OR, 1.19; p = 0.08).Racial disparities in lung transplantation have decreased with the implementation of LAS as the method of organ allocation; however, gender disparities may have actually increased in the LAS era.

The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed.

Slow delayed rectifier potassium current (IKs) is important in action potential (AP) repolarization and repolarization reserve. We tested the hypothesis that there are sex-specific differences in IKs, AP, and their regulation by β-adrenergic receptors (β-AR's) using whole-cell patch-clamp. AP duration (APD90) was significantly longer in control female (F) than in control male (M) myocytes. Isoproterenol (ISO, 500 nM) shortened APD90 comparably in M and F, and was largely reversed by β1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 μM) resulted in less APD prolongation in F at baseline (3.0 vs 8.9 %, p < 0.05 vs M) and even in the presence of ISO (5.4 vs 20.9 %, p < 0.05). This suggests that much of the ISO-induced APD abbreviation in F is independent of IKs. In F, baseline IKs was 42 % less and was more weakly activated by ISO (19 vs 68 % in M, p < 0.01). ISO enhancement of IKs was comparably attenuated by CGP in M and F. After ovariectomy, IKs in F had greater enhancement by ISO (72 %), now comparable to control M. After orchiectomy, IKs in M was only slightly enhanced by ISO (23 %), comparable to control F. Pretreatment with thapsigargin (to block SR Ca release) had bigger impact on ISO-induced APD shortening in F than that in M (p < 0.01). In conclusion, we found that there are sex differences in IKs, AP, and their regulation by β-AR's that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.

OBJECTIVE Many neurosurgical training programs have moved from a 24-hour resident call system to a night float system, but the impact on outcomes is unclear. Here, the authors compare length of stay (LOS) for neurosurgical patients admitted before and after initiation of a night float system at a tertiary care training hospital. METHODS The neurosurgical residency at the University of Alabama at Birmingham transitioned from 24-hour call to a night float resident coverage system in July 2013. In this cohort study, all patients admitted to the neurosurgical service for 1 year before and 1 year after this transition were compared with respect to hospital and ICU LOSs, adjusted for potential confounders. RESULTS A total of 4619 patients were included. In the initial bivariate analysis, night float was associated with increased ICU LOS (p = 0.032) and no change in overall LOS (p = 0.65). However, coincident with the transition to a night float system was an increased frequency of resident service transitions, which were highly associated with hospital LOS (p < 0.01) and ICU LOS (p < 0.01). After adjusting for resident service transitions, initiation of the night float system was associated with decreased hospital LOS (p = 0.047) and no change in ICU LOS (p = 0.35). CONCLUSIONS This study suggests that a dedicated night float resident may improve night-to-night continuity of care and decrease hospital LOS, but caution must be exercised when initiation of night float results in increased resident service transitions.

Glioblastoma multiforme (GBM) is rare, yet it is the most common brain malignancy and has a poor prognosis. In regard to GBM, there is a dearth of research on resting energy expenditure (REE) and the accuracy of extant prediction equations. The aim of this cross-sectional study was to compare measured REE (mREE) to commonly used prediction equations in newly diagnosed GBM patients. REE was collected by indirect calorimetry in 20 GBM patients. Calculated REE was derived from Harris-Benedict (again with weight adjusted for obesity), Mifflin-St Jeor, and the 20 kcal/kg body weight ratio method. Paired t-tests and Bland-Altman analyses were used to compare group means, evaluate the bias, and find the limits of agreement. Clinical accuracy was assessed by determining the percentage of patients with predicted REE within ±10% of mREE. Subjects were evenly distributed with regard to gender, primarily Caucasian, and largely overweight or obese and had a mean age of 57 years. All equations overestimated mREE. Mifflin-St Jeor and adjusted Harris-Benedict had the narrowest limits of agreement and accurately predicted 60% and 65% of subjects, respectively. Clinicians should be aware of the discrepancy between commonly used prediction equations and REE. More research is needed to verify these findings and decipher the cause and significance in the GBM population.

The ideal adjuvant therapy for resected cholangiocarcinoma remains controversial. National guidelines stratify recommendations based on margin status, though few studies are currently available for reference.Data was abstracted on all patients with definitive resections of cholangiocarcinoma at our institution between 2000 and 2013. Adjuvant chemoradiation consisted of 45 Gy delivered to elective nodal regions and 50.4-54 Gy to the surgical bed with concurrent fluoropyrimidine-based chemotherapy. Subgroup analyses were performed delineated by margin status.Curative resection was performed on 95 patients followed by adjuvant chemoradiation in 23/95 (24%) and observation in 72/95 (76%) with a median follow-up of 21.7 months. For those receiving adjuvant chemoradiation the median overall survival was 30.2 months compared with 26.3 months for those observed (p = 0.0695). In a multivariable model controlling for other prognostic factors, adjuvant chemoradiation was associated with improved disease-free survival (HR 0.50, p = 0.03) and overall survival (HR 0.37, p = 0.004). In multivariable models stratified by margin status, adjuvant chemoradiation was associated with improved overall survival following both margin-negative (HR 0.34, p = 0.035) and margin-positive (HR 0.15, p = 0.003) resections.Overall survival was improved with adjuvant chemoradiation following either margin-negative or margin-positive resections, which is not currently reflected in national guidelines.

Thrombotic thrombocytopenic purpura (TTP) has90% mortality without therapeutic plasma exchange (TPE). Despite TPE, approximately 10% of patients still die, presumably from cardiac ischemia. We sought clinical or laboratory parameters associated with death by reviewing the records of all patients hospitalized with acquired TTP in our institution for 10 years, and collect demographics and results for hemoglobin, platelet count, creatinine, lactate dehydrogenase, transaminases, total bilirubin, creatinine kinase (CK), CK-MB, and troponin I. Sixty-eight patients were admitted 88 times, and 11 died. Survivors and non-survivors were similar in terms of sex, ethnicity, thrombocytopenia, and degree of anemia at presentation, while the latter were older, had worse renal function and higher CK, CK-MB, and troponin I (univariate analysis). However, only troponin I remained significant on multivariate analyses. We propose that patients with TTP should be monitored with troponin I to detect significant myocardial ischemia that could predict death despite TPE.

The clinical benefit of newborn screening (NBS) for cystic fibrosis (CF) has been primarily nutritional, with less overt respiratory impact. Identification of risk factors for infant CF lung disease could facilitate targeted interventions to improve pulmonary outcomes.This retrospective study evaluated socioeconomic information, clinical data, and results from routine infant pulmonary function testing (iPFT) of infants diagnosed with CF through NBS (N = 43) at a single CF center over a 4-year period (2008-2012). A five-item composite clinical score was developed and combined with socioeconomic indicators to facilitate identification of CF infants at increased risk of early-onset respiratory impairment.Paternal education was positively associated with lung function (P = 0.02). Clinical score7 (on a scale of 0-10) predicted diminished pulmonary measure (P 0.005). Retrospective risk stratification by clinical score and paternal education identified CF infants at low, intermediate, or high risk of pulmonary disease. Forced expiratory volume (FEVWe combined socioeconomic and clinical data to risk-stratify CF infants for early-onset lung disease as quantified by iPFT. Our model showed significant differences in infant pulmonary function across risk groups. The developed tool offers an easily available, inexpensive, and non-invasive way to assess risk of respiratory decline in CF infants and identify those meriting targeted therapeutic attention. Pediatr Pulmonol. 2016;51:1168-1176. © 2016 Wiley Periodicals, Inc.

To describe cardiometabolic risk among a sample of American Indian women with previous gestational diabetes and describe the women's knowledge, risk perception for type 2 diabetes and cardiovascular disease, and self-efficacy beliefs related to preventing these diseases.Mixed methods, cross-sectional, exploratory, descriptive.Four campuses within one American Indian tribal health care system in a southwestern state.A purposeful sample of 22 self-identified American Indian women with a history of gestational diabetes.Qualitative interview data were subjected to content analysis, and descriptive statistics were used to analyze quantitative questionnaire data and biophysiologic data.The majority of participants (13 of 21) were classified as having metabolic syndrome, and 13 of 18 women were found to be insulin resistant. In general, the women had high levels of knowledge related to type 2 diabetes and cardiovascular disease and high risk perception, but low self-efficacy related to preventing cardiometabolic disease. The overarching theme from the in-depth interviews, struggling to change lifestyle behaviors while doubting prevention is possible, encompassed four categories that provided further illumination into participants' risk perceptions and self-efficacy beliefs: concerns, control, beliefs/attitudes, and prevention.High levels of knowledge and risk perception do not necessarily promote increased self-efficacy to prevent cardiometabolic disease among American Indian women with previous gestational diabetes. Findings indicate the need to further explore women's self-efficacy beliefs in the context of American Indian culture prior to developing interventions aimed at increasing self-efficacy to prevent or delay type 2 diabetes and cardiovascular disease. Women with previous gestational diabetes are at increased risk for developing cardiovascular disease, independent of a diagnosis of type 2 diabetes.

Several reports suggest that folate has a procarcinogenic effect. Folate has a unique role because its coenzymes are needed for de novo purine and thymine nucleotide biosynthesis. Antifolates, such as methotrexate, are used in cancer treatment. Using a meta-analysis weighted for the duration of folic acid (pteroylglutamic acid) supplementation, we analyzed the cancer incidence of six previously published large prospective folic acid-supplementation trials in men and women. These articles were carefully selected from over 1100 identified using PubMed search. Our analyses suggest that cancer incidences were higher in the folic acid-supplemented groups than the non-folic acid-supplemented groups (relative risk=1.21 [95% confidence interval: 1.05-1.39]). Folic acid-supplementation trials should be performed with careful monitoring of cancer incidence. Solid monitoring systems to detect side effects, including increase in cancer risk, should be established before the initiation of folic acid supplementation trials.

To conduct a telephone survey establishing pancreatic cancer survivors’ level of interest in, preferences for, and perceived barriers and facilitators to participating in exercise and diet intervention programming. These data will inform the development of such interventions for newly-diagnosed patients. Seventy-one survivors treated for resectable pancreatic adenocarcinoma from October 2011 to August 2014 were identified through an institutional cancer registry and contacted via telephone. A telephone survey was conducted to query survivors’ level of interest in, preferences for, and perceived barriers and facilitators to participating in an exercise and dietary intervention program shortly after disease diagnosis. Acceptability of a technology-based visual communication (e.g., Skype™, FaceTime®) intervention was also assessed. Fifty participants completed the survey (response rate 71.8 %). Over two-thirds of participants reported interest in exercise and diet intervention programming. Over half reported comfort with a technology-delivered visual communication intervention. Barriers to participation included older age and physical, personal, and emotional problems. The most common facilitator was program awareness. Outcomes for future research important to participants were supportive care and quality of life. Most pancreatic cancer patients are interested in exercise and diet interventions shortly after diagnosis; however, some barriers to program participation exist. Future research and intervention planning for pancreatic cancer survivors should focus on developing messaging and strategies that provide support for survivorship outcomes, increase survivor awareness, address lack of familiarity with technology, reduce fears about potential barriers, and help survivors overcome these barriers. In so doing, survivorship needs can be better met and quality of life improved in this understudied population.

Calcium intake is reported to enhance weight loss with a preferential loss in trunk fat. Discrepant findings exist as to the effects of calcium intake on longitudinal changes in total fat mass and central fat deposition. Therefore, the purpose of this study was to determine associations between dietary calcium intake and 1-year change in body composition and fat distribution, specifically intra-abdominal adipose tissue (IAAT). A total of 119 healthy, premenopausal women were evaluated at baseline and 1 year later. Average dietary calcium was determined via 4-day food records. Total fat was determined by dual-energy X-ray absorptiometry (DXA) and subcutaneous abdominal adipose tissue (SAAT) and IAAT by computed tomography. Over the study period, participants' reported daily calcium and energy intakes were 610.0 ± 229.9 mg and 1,623.1 ± 348.5 kcal, respectively. The mean change in weight, total fat, IAAT, and SAAT was 4.9 ± 4.4 kg, 5.3 ± 4.0 kg, 7.7 ± 19.5 cm(2), and 49.3 ± 81.1 cm(2), respectively. Average calcium intake was significantly, inversely associated with 1-year change in IAAT (standardized β: -0.23, P0.05) after adjusting for confounding variables. For every 100 mg/day of calcium consumed, gain in IAAT was reduced by 2.7 cm(2). No significant associations were observed for average calcium intake with change in weight, total fat, or SAAT. In conclusion, dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women. Further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution.

We compared the effects of an 8‐week iso‐caloric high‐protein (HP) diet versus a combined exercise regimen (Comb‐Ex) in individuals with long‐standing spinal cord injury (SCI). Effects on metabolic profiles, markers of inflammation, and signaling proteins associated with glucose transporter 4 (GLUT‐4) translocation in muscles were evaluated. Eleven participants with SCI completed the study (HP diet: n = 5; Comb‐Ex: n = 6; 46 ± 8 years; C5‐T12 levels; American Spinal Injury Association Impairment Scale A or B). The Comb‐Ex regimen included upper body resistance training (RT) and neuromuscular electrical stimulation‐induced‐RT for paralytic quadriceps muscles, interspersed with high‐intensity (80–90% VO2 peak) arm cranking exercises 3 days/week. The HP diet included ~30% total energy as protein (carbohydrate to protein ratio

(1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment.Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0-300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens.Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients.Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.

Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin(0)), the acute insulin response to glucose (AIR(g)), the insulin sensitivity index (S(I)), basal and nadir FFA (FFA(0), FFA(nadir)), and nadir time (TIME(nadir)) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA(0), FFA(nadir), and TIME(nadir) with ethnicity, age group, insulin measures, indexes of body composition from dual-energy X-ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin(0) and AIR(g) were higher among AAs vs. EAs, whereas S(I) was lower, independent of age group. MLR analyses indicated that FFA(0) was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), S(I), and insulin(0). FFA(nadir) was best predicted by FFA(0), age group, and intra-abdominal adipose tissue (IAAT). TIME(nadir) was best predicted by leg fat mass, AIR(g), and S(I). In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA(0) among AAs was independent of insulin(0) and S(I). Whether lower FFA(0) is associated with substrate oxidation or risk for obesity remains to be determined.

Rationale Transforming factor β1 (TGF-β1) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-β1 protein levels and clinical markers of CF lung disease severity. Objectives To determine the association between protein levels of TGF-β1 in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity. Methods Total TGF-β1 was measured in BALF from 30 pediatric CF patients and 12 non-CF disease controls undergoing clinically indicated flexible bronchoscopy, and compared to four indicators of clinical disease: infection, inflammation, pulmonary function, and recent/recurrent hospitalization. Results TGF-β1 was elevated in CF BALF compared to non-CF controls (135 ± 15 pg/ml vs. 57 ± 10 pg/ml, P

Purpose Acute kidney injury in the pediatric intensive care unit (PICU) is associated with significant morbidity, with continued mortality greater than 50%. Previous studies have described an association between percentage of fluid overload (%FO) less than 20% and improved survival. We reviewed our continuous renal replacement therapy (CRRT) experience to evaluate for factors associated with mortality as well as secondary outcomes. Materials and Methods This is a retrospective chart review of pediatric CRRT intensive care unit patients from January 2000 to September 2005. Results Seventy-six admissions required CRRT during the study period. Overall survival was 55.3%. Median patient age was 5.8 years (range, 0-18.9). Median %FO at the time of CRRT initiation was 7.3% in survivors vs 22.3% in nonsurvivors ( P = .0001). Presence of sepsis was significantly associated with mortality ( P = .0001). All nonsurvivors had multiple organ dysfunction syndrome (MODS); only 69% of survivors had MODS ( P = .0003). For survivors, there was a significant relationship between %FO and time to renal recovery ( P = .0038). Greater %FO was also associated with significantly prolonged days of mechanical ventilation ( P = .0180), PICU stay ( P = .0425), and duration of hospitalization ( P = .0123). Conclusions For patients with acute kidney injury who require CRRT, the presence of sepsis, MODS, and FO greater than 20% at the time of CRRT initiation are significantly associated with higher mortality. In addition, we report that duration of mechanical ventilation, PICU stay, hospitalization, and time to renal recovery were all significantly prolonged for survivors who had FO greater than 20%.

Background: Overweight children have greater circulating concentrations of markers of inflammation (MOI) than do lean children. Whether adiposity influences the postprandial MOI response is unknown. Objective: We aimed to evaluate the relations of fasting and postprandial MOI with total and regional adiposity and insulin sensitivity in children. Design: Fifty-nine children aged 7–12 y were assessed for C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptor-2 (sTNF-R2) in the fasted state and after a mixed meal. Insulin sensitivity, body composition, and abdominal adipose tissue distribution were assessed with a frequently sampled intravenous-glucose-tolerance test, dual-energy X-ray absorptiometry, and computed tomography, respectively. Results: Central adipose measures were not independently associated with fasting MOI, although they were independently inversely associated with the postprandial sTNF-R2 response (r = −0.30 to −0.37, P = 0.02–0.006). The inverse association between intraabdominal adipose tissue and the postprandial CRP response was nearly significant (r = −0.27, P = 0.05). Insulin sensitivity was not associated with fasting or postprandial CRP or sTNF-R2; however, there was a positive relation between insulin sensitivity and fasting IL-6 (r = 0.27, P = 0.03), which was attenuated after adjustment for lean body mass (r = 0.25, P = 0.08). Conclusions: Excess adiposity is associated with both fasting and postprandial MOI. The postprandial MOI response may be influenced by central adiposity in children. The positive association of insulin sensitivity with IL-6 warrants further study.

OBJECTIVE—The aim of this study was to examine the association of physical activity with glucose tolerance and resting energy expenditure (REE) among adolescents. RESEARCH DESIGN AND METHODS—Subjects were 32 male and female adolescents aged 12–18 years. Intravenous glucose tolerance (Kg) and REE were assessed under inpatient conditions after an overnight fast. Kg was determined as the inverse slope of time versus (ln) glucose over minutes 8–19 of an intravenous glucose tolerance test. Physical activity was assessed over 8 days using accelerometry (counts per minute). RESULTS—In multiple linear regression analysis, Kg was positively associated with total physical activity (TPA), moderate physical activity (MPA), and 5-min bouts of MPA. Similarly, REE was positively associated with TPA, MPA, and 5-min bouts of MPA. CONCLUSIONS—In this population, physical activity was positively related to both glucose tolerance and REE. These results suggest that moderate activity may be beneficial in the prevention of diabetes in adolescent populations both through promoting efficient glucose disposal and through increasing energy expenditure.

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.

BACKGROUND: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a diagnosis of exclusion when a patient presents with the sine qua non findings of thrombocytopenia and microangiopathic hemolytic anemia without an identifiable cause. Although most patients respond to therapeutic plasma exchange (TPE), a significant number of patients relapse. The aim was to determine if clinical, laboratory, and/or treatment features could predict response and/or relapse. STUDY DESIGN AND METHODS: This study was a retrospective review of adults with TTP-HUS treated with TPE at our institution from January 1996 to February 2004. RESULTS: The study population consisted of 90 patients (69% female) with mean age of 45 years and mostly obese (65%). The majority of cases were considered idiopathic. Ten patients died (11%) from the disease before achieving a response, whereas 79 percent were considered responders. Obesity and severe anemia at presentation were predictors of response to TPE (p = 0.0126 and p = 0.0071, respectively). Among the responders, 28 percent relapsed in a median of 14 months. Male sex, severe thrombocytopenia (mean ± SD, 13 × 109 ± 8 × 109/L), and higher lactate dehydrogenase pre-/posttreatment ratio were associated with relapse (p values of 0.0141, 0.0199, and 0.0407, respectively). ADAMTS-13 values were not obtained on enough number of patients to provide important data. CONCLUSION: Although patient and laboratory characteristics associated with response and relapse were identified, there was significant overlap between patient groups. Thus, our findings offer preliminary evidence and do not yet justify short- or long-term changes in the management of patients with TTP-HUS.

To evaluate and compare sequential ultrasound exams (US) with power-Doppler (PD) to radiography for the detection of synovitis and erosions in patients with early RA.Radiographs and US with PD of the hands and feet were performed at baseline and 6+/- 2 months afterwards in 21 early RA patients. Their mean (range) age was 42.6 (21-81) years and the female/male ratio was 4:3; mean disease duration was 9 (1-28) months. Joints assessed were bilateral 2nd and 5th MCPs, 5th MTPs and the most swollen PIP in each hand, for a total of eight joints per patient. Radiographs (PA, lateral and pronated oblique) were read for erosions using the method of Sharp/van der Heijde. On US, erosions were defined as cortical defects greater than 2 mm in diameter with an irregular floor. Synovitis was rated as +1 (increase in joint fluid without synovial hyperemia), +2 (mild blood flow), +3 (moderate blood flow), and +4 (severe blood flow). Two blinded trained assessors read all images.US detected 15 erosions in 10 patients at baseline and 31 erosions in 12 patients on follow-up; radiographs could detect only one erosion at baseline and five erosions in three patients on follow-up. PD detected synovitis in all patients at baseline and on follow-up. Of the joints found to have synovitis, 64% were identified as such at baseline and 38% on follow-up.Sequential US can determine disease progression in patients with early RA. Such data may allow the clinician to treat RA patients earlier in the hope of preventing joint damage.

Objective To test the hypothesis that the dietary intake and dietary composition of women with polycystic ovary syndrome (PCOS) is associated with indices of glycemic status. We hypothesized that women with PCOS would consume a diet higher in total energy, fat, and specific foods with a high glycemic index than would healthy, control-group women and that dietary composition would be associated with indices of insulin resistance and secretion among women with PCOS. Design Cohort study. Setting Research center on a university campus. Patient(s) Thirty women with PCOS and 27 healthy, age-, race-, and body mass index (BMI)–matched control women. Intervention(s) None. Main Outcome Measure(s) Nutrient intake data were collected from a food questionnaire and a 4-day food record. Fasting sera were analyzed for concentrations of insulin and glucose; estimates of insulin resistance were calculated. Result(s) Consumption of total energy, macronutrients, micronutrients, and high glycemic index foods was similar between the groups. However, the PCOS group consumed significantly more white bread (7.9 ± 4.4 vs. 5.5 ± 2.9 servings over 4 days) and tended to consume more fried potatoes than did the control group (1.0 ± 1.5 vs. 0.4 ± 0.7 servings over 4 days). The PCOS group had a significantly greater fasting insulin concentration (22.5 ± 14.9 vs. 15.1 ± 8.3 μIU/mL) and a significantly lower glucose-to-insulin ratio (4.7 ± 2.1 vs. 7.6 ± 5.2) than the control group. Within the PCOS group, HOMA-IR and HOMA-%β-cell function were significantly associated with BMI. The HOMA-IR, HOMA-%β-cell, fasting insulin, and glucose-to-insulin ratio were not positively associated with measures of diet composition. Conclusion(s) Compared with matched control women, women with PCOS exhibited a dietary pattern that was marked by consumption of a greater amount of specific foods with a high glycemic index; however, diet composition was not associated with the greater fasting insulin concentration or with lower glucose-to-insulin ratio that was observed in the PCOS group.

Objective: To determine whether activity counts obtained with the Actiwatch monitor are associated with total expenditure and body composition in young children. Research Methods and Procedures: Actiwatch activity monitors were tested in 29 children 4 to 6 years old under field conditions over eight days. Total energy expenditure (TEE) was assessed with the doubly labeled water (DLW) technique. Correlation analyses were used to identify variables related to energy expenditure and percentage body fat. Multiple linear regression analyses were used to examine the variance in TEE and percentage body fat explained by activity counts after adjusting for relevant covariates. Results: Both average total daily activity counts (658, 816 ± 201, 657) and the pattern of activity were highly variable among subjects. TEE was significantly related to lean body mass (r = 0.45) and age (r = 0.48; p < 0.05 for both). Activity counts alone were not associated with TEE. In multiple linear regression analyses, TEE was independently associated with only lean body mass. Percentage fat mass was independently associated with body weight, being a girl, and being white, but not with average total activity counts. Discussion: Activity counts obtained with the Actiwatch under free-living conditions do not reflect TEE in 4- to 6-year-old children and are not correlated with percentage fat mass. Therefore, average total activity counts obtained with the Actiwatch may be of limited value in identifying children at risk for becoming obese.

Background Moderate alcohol consumption increases plasma HDL and lowers cardiovascular disease risk while transiently enhancing postprandial lipemia. Objective We hypothesized that the alcohol-mediated increase in postprandial triacylglycerol-rich lipoproteins (TRLs) and their clearance elevate HDL cholesterol and reverse cholesterol transport. Design We determined the effect in normolipidemic humans (n = 14) of postprandial lipemia produced 4 h after a test meal (M) or a test meal + 0.5 g alcohol/kg body wt (M+A) on postprandial changes in plasma lipids and on the balance of cholesterol between TRL and the cholesterol-rich LDL and HDL fractions (CRL) or red blood cells (RBCs) in fresh and incubated plasma or blood. Results Postprandial lipemia after the M and M+A test meals caused a 56% and 89% increase in plasma triacylglycerol, a 30% and 74% increase in TRL cholesterol, and a 3.8% and 6.6% decrease in CRL cholesterol, respectively. In vitro reaction of endogenous lecithin:cholesterol acyltransferase (EC 2.3.1.43) and cholesteryl ester transfer proteins via incubation of fasting plasma samples and postprandial M and M+A plasma samples for 16 h increased TRL cholesterol by 22.8% (0.08 mmol/L), 32.6% (0.16 mmol/L), and 45.8% (0.28 mmol/L) in plasma and by 71.1% (0.27 mmol/L), 89.4% (0.45 mmol/L), and 112.5% (0.70 mmol/L) in RBC-enriched blood, respectively. After the in vitro lipolysis of TRL, the elevation of HDL cholesterol in postprandial M+A plasma, but not in postprandial M plasma, was significantly greater than in fasting plasma. Conclusion The alcohol-mediated increase in postprandial TRL flux and the hepatic removal of postprandial TRL after the acceptance of cholesterol from CRL and cell membranes contribute to increased HDL cholesterol and enhancement of reverse cholesterol transport in humans.

Using a large sample of colorectal cancer (CRC) survivors we 1) describe pain interference (PI) prevalence across the cancer continuum; 2) identify demographic and clinical factors associated with PI and changes in PI; and 3) examine PI's relationship with survivors' job changes.CRC participants of the Cancer Care Outcomes Research and Surveillance Consortium completed surveys during the initial phase of care (baseline, 1 year, n = 2,961) and follow-up (about 1-year postdiagnosis, n = 2,303). PI was measured using the SF-12 item. Multiple logistic regression was used to identify predictors of PI. Model 1 evaluated moderate/high PI at baseline, Model 2 evaluated new/continued/increasing PI postdiagnosis follow-up, and Model 3 restricted to participants with baseline PI (N = 603) and evaluated predictors of equivalent/increasing PI. Multivariable logistic regression was also used to examine whether PI predicted job change.At baseline and follow-up, 24.7% and 23.7% of participants reported moderate/high PI, respectively. Among those with baseline PI, 46% had equivalent/increasing PI at follow-up. Near diagnosis and at follow-up, female gender, comorbidities, depression, chemotherapy and radiation were associated with moderate/high PI while older age was protective of PI. Pulmonary disease and heart failure comorbidities were associated with equivalent/increasing PI. PI was significantly associated with no longer having a job at follow-up among employed survivors.Almost half of survivors with PI during the initial phase of care had continued PI into post-treatment. Comorbidities, especially cardiovascular and pulmonary conditions, contributed to continued PI. PI may be related to continuing normal activities, that is, work, after completed treatment.

African Americans are less likely than other groups to receive appropriate surveillance after colorectal cancer (CRC) treatment. The objective of this study is to qualitatively explore the role of social support in post-CRC treatment surveillance and ultimately, inform interventions to promote surveillance in African American survivors of CRC. Interviews were conducted with 60 African American survivors of CRC recruited from the Cancer Care Outcomes Research and Surveillance (CanCORS) study and the Alabama Statewide Cancer Registry. Interviews were recorded and transcribed. Transcripts were reviewed and coded independently by the authors. The NVivo software package was used to facilitate coding and data management. Survivors were from 4 to 6 years post diagnosis, 57% female, 60% older than age 65 years, 57% from rural Alabama, 30% with stage 1, 32% with stage 2, and 38% with stage 3 disease. Material and emotional social support from family and one's faith community were cited as playing an important role in coping with the disease and posttreatment surveillance. Survivors who reported being adherent with posttreatment surveillance recommendations (according to stage of disease based on self-report of colonoscopy, computed tomography scans, and blood work) reported more religious material and non-material social support, and support from other survivors of CRC. In these African American survivors of CRC, support from family, other survivors of cancer, and the faith community was perceived as being important for adherence to posttreatment surveillance. Interventions to increase posttreatment surveillance in this population may be enhanced by including components that emphasize familial, other cancer survivor, and religious support.

Background Cigarette smoking causes Chronic Obstructive Pulmonary Disease (COPD), the 3rd leading cause of death in the U.S. CFTR ion transport dysfunction has been implicated in COPD pathogenesis, and is associated with chronic bronchitis. However, susceptibility to smoke induced lung injury is variable and the underlying genetic contributors remain unclear. We hypothesized that presence of CFTR mutation heterozygosity may alter susceptibility to cigarette smoke induced CFTR dysfunction. Consequently, COPD patients with chronic bronchitis may have a higher rate of CFTR mutations compared to the general population. Methods Primary human bronchial epithelial cells derived from F508del CFTR heterozygotes and mice with (CFTR+/-) and without (CFTR+/+) CFTR heterozygosity were exposed to whole cigarette smoke (WCS); CFTR-dependent ion transport was assessed by Ussing chamber electrophysiology and nasal potential difference measurements, respectively. Caucasians with COPD and chronic bronchitis, age 40 to 80 with FEV1/FVC

African Americans are less likely than other racial/ ethnic groups to receive appropriate surveillance, an important component of care to achieve better long-term outcomes and well- being after colorectal cancer (CRC) treatment. This study explored survivors' understanding of surveillance instructions and purpose. Patients and Methods: Interviews with 60 African American CRC survivors were recorded and transcribed. Compliance with surveillance guidelines was defined by disease stage and self- reported tests. Four coders (blind to compliance status) indepen- dently reviewed transcripts. Frequency of themes was reported by compliance status. Results: Survivors (4 to 6 years postdiagnosis; women, 57%; age 65 years, 60%; rural location, 57%; early-stage disease, 62%) were 48% noncompliant. Most survivors re- ported receiving surveillance instructions from providers (compliant, 80%; noncompliant, 76%). There was variation in recommended frequency of procedures (eg, every 3 or 12 months) and in importance of surveillance stressed by physicians. Most survivors understood the need for follow-up (compliant, 87%; noncom- pliant, 79%). Lack of knowledge of/interest in surveillance was more common among noncompliant individuals (compliant, 32%; noncom- pliant, 52%). Conclusion: Patients' limited understanding about the im- portance of CRC surveillance and procedures may negatively affect compliance with recommendations in African American CRC survivors. Clear and enhanced communications about post-treatment recommendations in this population are warranted.

Objective: This study aimed to characterize the prevalence of non-diabetic renal disease among African-Americans (AA) with type II diabetes mellitus based on a biopsy series. No previous study has investigated the nature of renal lesions in AA with type II DM. Material and methods: Thirty AA patients with type II DM who were being managed at an inner-city hospital had kidney biopsies to evaluate suspected non-diabetic renal disease (NDRD) between 1994 and 1998. The demographic, clinical and histopathological data on these patients were analysed retrospectively. Kidney biopsies were reviewed by light microscopy, immunofluorescence and electron microscopy. Results and conclusions: Three patterns of glomerular disease were observed. Diabetic nephropathy alone was seen in 13 patients (41.9%), diabetic nephropathy coexisted with glomerulonephritis in 12 patients (38.7%), while NDRD was seen in six patients (19.4%).