Palliative care among adult cancer survivors: Knowledge, attitudes, and correlates.

OBJECTIVE: Palliative care (PC) is patient and family-centered supportive care intended to improve symptom management, reduce caregiver burden, coordinate care, and improve quality of life for patients diagnosed with serious illness. Optimally, PC is begun close to initial diagnosis and delivered in synchrony with disease-specific treatment until symptom relief or patient death. The purpose of this study was to examine cancer survivors' knowledge and perceptions of PC using a nationally representative sample of US adults from the Health Information National Trends Survey (HINTS). METHOD: A total of 593 HINTS respondents reported a personal history of cancer and were included in the sample (55.56% female; mean age of 65.88 years, SD = 18.21; mean time from diagnosis 13.83 years, SD = 18.21). Weighted logistic regression models were conducted to identify correlates of PC knowledge. RESULTS: Of the 593 cancer survivors in the sample, 66% (N = 378) reported that they had never heard of PC, 18% (N = 112) reported knowing a little bit about PC, and 17% (N = 95) reported knowing what PC is and could explain it to someone else. In multivariable analysis, survivors of color (Hispanic/Latino, Black, Asian, American Indian, and Pacific Islander), males, and those less educated were significantly less likely to report knowledge of PC. Among survivors who did report knowledge of PC, a lack of distinction between differing modes of supportive care exists. SIGNIFICANCE OF RESULTS: These findings suggest a need to increase PC knowledge among cancer survivors with the ultimate goal of addressing disparities in PC acceptance and utilization.

Brain biomarkers and neuropsychological outcomes of pediatric posterior fossa brain tumor survivors treated with surgical resection with or without adjuvant chemotherapy.

PURPOSE: Children with brain tumors experience cognitive late effects, often related to cranial radiation. We sought to determine differential effects of surgery and chemotherapy on brain structure and neuropsychological outcomes in children who did not receive cranial radiation therapy (CRT). METHODS: Twenty-eight children with a history of posterior fossa tumor (17 treated with surgery, 11 treated with surgery and chemotherapy) underwent neuroimaging and neuropsychological assessment a mean of 4.5 years (surgery group) to 9 years (surgery + chemotherapy group) posttreatment, along with 18 healthy sibling controls. Psychometric measures assessed IQ, language, executive functions, processing speed, memory, and social-emotional functioning. Group differences and correlations between diffusion tensor imaging findings and psychometric scores were examined. RESULTS: The z-score mapping demonstrated fractional anisotropy (FA) values were ≥2 standard deviations lower in white matter tracts, prefrontal cortex gray matter, hippocampus, thalamus, basal ganglia, and pons between patient groups, indicating microstructural damage associated with chemotherapy. Patients scored lower than controls on visuoconstructional reasoning and memory (P ≤ .02). Lower FA in the uncinate fasciculus (R = -0.82 to -0.91) and higher FA in the thalamus (R = 0.73-0.91) associated with higher IQ scores, and higher FA in the thalamus associated with higher scores on spatial working memory (R = 0.82). CONCLUSIONS: Posterior fossa brain tumor treatment with surgery and chemotherapy affects brain microstructure and neuropsychological functioning years into survivorship, with spatial processes the most vulnerable. Biomarkers indicating cellular changes in the thalamus, hippocampus, pons, prefrontal cortex, and white matter tracts associate with lower psychometric scores.

Low Rate of Intrathecal Baclofen Pump Catheter-Related Complications: Long-Term Study in Over 100 Adult Patients Associated With Reinforced Catheter.

OBJECTIVES: Intrathecal baclofen (ITB) is a cost-effective therapy for patients with severe spasticity. The most common complications are catheter-related complications (CRCs) including kinking/occlusion, blockage, migration, fracture, disconnection, and CSF leak. Our objective was to determine the CRC rate in a large cohort of adults with newly implanted ITB pump systems with polymer reinforced silicone catheters. MATERIALS AND METHODS: This is a retrospective study of a prospectively maintained database consisting of patients who had undergone implantation of ITB pump systems with Ascenda (Medtronic, Minneapolis) catheters from 2013 to 2020. Over this seven-year period, 141 patients underwent ITB pump system implantations; 126 of which had a minimum of one-year follow-up. RESULTS: The 126 patients with a minimum of one year follow-up (average 43 month; range 12-89), had an average age of 51 years (63% male). Severe spasticity was due to spinal cord injury (38%), traumatic brain injury (15%), cerebral palsy (13%), multiple sclerosis (11%), stroke (10%), and other (13%). Nine (7.1%) CRCs occurred in 7 (5.6%) patients (median 6 mo. post-implant): 5 intrathecal catheter occlusions (range 3-52 months post-implant), two fractures in one patient (6 months), one disconnection at the catheter pump interface (2 months), and one due to kinking at 84 months No migrations occurred. CONCLUSIONS: Reported CRCs have been high for ITB pump systems. Ours is the first large cohort, long-term study of CRCs related to reinforced catheters; additionally, our low CRC rate compares favorably to previously published data. Thus, implantation of reinforced catheters may be associated with a low CRC rate.

Maturation of Brain Microstructure and Metabolism Associates with Increased Capacity for Self-Regulation during the Transition from Childhood to Adolescence.

Children ages 9-12 years face increasing social and academic expectations that require mastery of their thoughts, emotions, and behavior. Little is known about the development of neural pathways integral to these improving capacities during the transition from childhood to adolescence. Among 234 healthy, inner-city male and female youth (species Homo sapiens) 9-12 years of age followed by the Columbia Center for Children's Environmental Health, we acquired diffusion tensor imaging, multiplanar chemical shift imaging, and cognitive measures requiring self-regulation. We found that increasing age was associated with increased fractional anisotropy and decreased apparent diffusion coefficient, most prominently in the frontal and cingulate cortices, striatum, thalamus, deep white matter, and cerebellum. Additionally, we found increasing age was associated with increased N-acetyl-l-aspartate (NAA) in the anterior cingulate and insular cortices, and decreased NAA in posterior cingulate and parietal cortices. Age-associated changes in microstructure and neurometabolite concentrations partially mediated age-related improvements in performance on executive function tests. Together, these findings suggest that maturation of key regions within cortico-striatal-thalamo-cortical circuits subserve the emergence of improved self-regulatory capacities during the transition from childhood to adolescence.SIGNIFICANCE STATEMENT Few imaging studies of normal brain development have focused on a population of inner-city, racial/ethnic minority youth during the transition from childhood to adolescence, a period when self-regulatory capacities rapidly improve. We used DTI and MPCSI to provide unique windows into brain maturation during this developmental epoch, assessing its mediating influences on age-related improvement in performance on self-regulatory tasks. Our findings suggest that rapid maturation of cortico-striato-thalamo-cortical circuits, represented as progressive white-matter maturation (increasing FA and increasing NAA, Ch, Cr concentrations accompanying advancing age) in frontal regions and related subcortical projections and synaptic pruning (decreasing NAA, Ch, Cr, Glx) in posterior regions, support age-related improvements in executive functioning and self-regulatory capacities in youth 9-12 years of age.

Lung Microbiota Is Related to Smoking Status and to Development of Acute Respiratory Distress Syndrome in Critically Ill Trauma Patients.

RATIONALE: Cigarette smoking is associated with increased risk of acute respiratory distress syndrome (ARDS) in patients after severe trauma; however, the mechanisms underlying this association are unknown. OBJECTIVES: To determine whether cigarette smoking contributes to ARDS development after trauma by altering community composition of the lung microbiota. METHODS: We studied the lung microbiota of mechanically ventilated patients admitted to the ICU after severe blunt trauma. To do so, we used 16S ribosomal RNA gene amplicon sequencing of endotracheal aspirate samples obtained on ICU admission (n = 74) and at 48 hours after admission (n = 30). Cigarette smoke exposure (quantified using plasma cotinine), ARDS development, and other clinical parameters were correlated with lung microbiota composition. MEASUREMENTS AND MAIN RESULTS: Smoking status was significantly associated with lung bacterial community composition at ICU admission (P = 0.007 by permutational multivariate ANOVA [PERMANOVA]) and at 48 hours (P = 0.03 by PERMANOVA), as well as with significant enrichment of potential pathogens, including Streptococcus, Fusobacterium, Prevotella, Haemophilus, and Treponema. ARDS development was associated with lung community composition at 48 hours (P = 0.04 by PERMANOVA) and was characterized by relative enrichment of Enterobacteriaceae and of specific taxa enriched at baseline in smokers, including Prevotella and Fusobacterium. CONCLUSIONS: After severe blunt trauma, a history of smoking is related to lung microbiota composition, both at the time of ICU admission and at 48 hours. ARDS development is also correlated with respiratory microbial community structure at 48 hours and with taxa that are relatively enriched in smokers at ICU admission. The data derived from this pilot study suggest that smoking-related changes in the lung microbiota could be related to ARDS development after severe trauma.

Intrathecal Baclofen Therapy in Patients With Multiple Sclerosis: Improved Outcomes and Reduced Costs Through Identification of Catheter Malfunction.

INTRODUCTION: Two patients previously implanted with intrathecal Baclofen (ITB) pumps for management of intractable spasticity due to multiple sclerosis (MS) were referred to our center for ongoing management of their spasticity. Initial evaluation of these patients revealed high levels of spasticity in the presence of ITB doses 10 times the average daily dose of our other MS patients. CLINICAL FACTS: High doses of ITB required frequent clinical visits and result in high drug and procedure costs. Both patients' daily doses were greater than 1000 mcg/day resulting in clinical visits every 1-2 months with drug and procedure costs ranging from 16 to 23 thousand dollars annually based on Medicare national average pricing for physician's office. Of the 59 MS patients receiving ITB therapy at our institution, the mean, median, and mode daily doses for ITB are 184, 115, and 159 mcg/day, respectively. The high ITB doses in these patients and poor spasticity control raised suspicion for pump/catheter malfunction and prompted immediate troubleshooting. FINDINGS: One patient's catheter was found to be disconnected from the pump and the other's catheter tip was outside the intrathecal space. In both cases, the patients were not receiving the therapy. After pump/catheter replacement, both patients received excellent clinical benefits from ITB at significantly lower daily doses. This reduction in dose resulted in decreased frequency of medication refills (twice annually) which resulted in decreased cost of care (12-19 thousand dollars savings annually per patient). DISCUSSION: These cases illustrate the need for early ITB pump troubleshooting to identify catheter problems, improve efficacy, and avoid unnecessary healthcare costs.

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity.

Purpose To determine whether treatment affects MRI signal intensity in pediatric patients with primary brain tumors independent of the administration of macrocyclic gadolinium-based contrast agents (GBCAs). Materials and Methods This retrospective, single-center study included 78 patients (mean age, 7.7 years ± 5.4) with primary brain tumors who underwent macrocyclic GBCA-enhanced MRI from 2015 to 2018. Three groups were compared: (a) patients who had undergone radiation therapy (37 patients, 26 of whom had undergone concurrent chemotherapy), (b) patients who had undergone chemotherapy only (17 patients), and (c) patients who had received no treatment ("no-treatment group," 24 patients). The signal intensity in the globus pallidus (GP), thalamus, dentate nucleus (DN), and pons was measured on unenhanced T1-weighted images. GP-to-thalamus and DN-to-pons signal intensity ratios were compared among groups with analysis of variance by using the Kruskal-Wallis test, followed by post hoc pairwise tests with Tukey adjustment, and were analyzed relative to group, total cumulative doses of GBCA, age, and sex with multivariable linear models. Results The mean number of GBCA-enhanced MRI examinations in the radiation therapy, chemotherapy-only, and no-treatment groups was 7.11, 7.29, and 4.96, respectively (P < .01 for the radiation therapy and chemotherapy groups compared with the no-treatment group). The DN-to-pons ratio in the radiation therapy group was higher than that in both the no-treatment group and the chemotherapy-only group (P < .01 for both). There was no significant difference in the DN-to-pons ratios between the chemotherapy-only group and the no-treatment group (P = .99). The GP-to-thalamus ratios did not differ among all three groups (P = .09). There was no dose-dependent effect of GBCA on the DN-to-pons and GP-to-thalamus ratios when adjusting for the effects of treatment (P = .21 and P = .38, respectively). Conclusion Brain irradiation contributes to a higher dentate nucleus signal intensity in pediatric patients with brain tumor independent of the administration of macrocyclic gadolinium-based contrast agents. © RSNA, 2018.

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.

Purpose To determine whether whole-brain irradiation, chemotherapy, and primary brain pathologic conditions affect magnetic resonance (MR) imaging signal changes in pediatric patients independent of the administration of gadolinium-based contrast agents (GBCAs). Materials and Methods This institutional review board-approved, HIPAA-compliant study included 144 pediatric patients who underwent intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy only, 52 with primary brain tumors without any treatment, and 18 with neuroblastoma without brain metastatic disease). The signal intensities (SIs) in the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared between groups by using the analysis of variance and were analyzed relative to group, total cumulative number of doses of GBCA, age, and sex by using multivariable linear models. Results DN:P ratio for the radiation therapy group was greater than that for the other groups except for the group of brain tumors treated with chemotherapy (P < .05). The number of GBCA doses was correlated with the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation therapy-treated brain tumor group demonstrated higher DN:P ratios than the nontreated brain tumor group for number of doses less than or equal to 10 (P < .0001), whereas ratios in the nontreated brain tumor group were higher than those in the radiation therapy-treated brain tumor group for doses greater than 20 (P = .05). The GP:T ratios for the brain tumor groups were greater than that for the neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are independent of the administration of GBCA occur in patients with brain tumors undergoing brain irradiation, as well as in patients with untreated primary brain tumors. © RSNA, 2017.

Measuring Nurse Caring Behaviors in the Hospitalized Older Adult.

OBJECTIVE: The aim of this study was to investigate the relationship between nurse caring behavior scores and the use of the "Get to Know Me" poster in hospitalized older adults. BACKGROUND: Hospitalization can be an isolating experience for the patient and his/her family. Within the high-tech healthcare arena, the focus of the "patient/person" can be lost. The art of caring and basic communication between the nurse and person is essential to nursing. METHODS: This was a 2-group quasi-experimental pretest-posttest design using the intervention of the Get to Know Me poster and measurement of nurse caring behaviors with the Caring Assessment of Care Givers (CACG) instrument. RESULTS: Nurse caring behavior scores of the nurses in the experimental group who utilized the Get to Know Me poster were significantly higher on the total CACG scores as well on the subscale dimensions of maintaining belief, being with, and doing for than those of the nurses forming the control group. CONCLUSIONS: The results of this research indicated that interventions that focus the attention on the person and emphasize patient-focused care can enhance nurse caring behaviors and strengthen the patient-nurse relationship.

Intrathecal Baclofen Dosing Regimens: A Retrospective Chart Review.

OBJECTIVES: To examine dosing patterns in patients receiving baclofen via intrathecal baclofen pumps to assess for common patterns by diagnosis, ambulation ability, and affected limbs distribution. MATERIALS AND METHODS: This trial study included 25 patients with baclofen pumps selected from the 356 patients enrolled in our center's baclofen pump program. Selection was done by splitting all patients into diagnostic categories of stroke, multiple sclerosis, traumatic/anoxic brain injury, cerebral palsy, and spinal cord injury, and then, five patients were randomly selected from each diagnosis.A systematic chart review was then conducted for each patient from Jan 1, 2008, through September 16, 2013, to look at factors including mean daily dose at end of study, and among those implanted during the study mean initial stable dose and time to initial stable dose. RESULTS: Analysis of mean daily dose across diagnoses found significant differences, with brain injury, cerebral palsy, and spinal cord injury patients having higher doses while multiple sclerosis and stroke patients required lower doses. Nonambulatory patients strongly trended to have higher daily doses than ambulatory patients. Similar trends of mean initial stable dose being higher in a similar pattern as that of end mean daily dose were seen according to diagnoses and ambulatory status, although statistical significance could not be achieved with the small sample size. CONCLUSION: Significant differences in dosing were found between diagnoses and trended to differ by ambulatory status at the end of the study, and similar trends could be observed in achieving initial stable dose.

Best Practices for Intrathecal Baclofen Therapy: Dosing and Long-Term Management.

INTRODUCTION: Intrathecal baclofen (ITB) therapy aims to reduce spasticity and provide functional control. METHOD: An expert panel consulted on best practices. RESULTS: Pump fill and drug delivery can be started intraoperatively, with monitoring for at least eight hours. Initiate with the 500 mcg/mL concentration. The starting daily dose should be twice the effective bolus screening dose, or the screening dose if the patient had a prolonged response (greater than eight hours) or negative reactions. Oral antispasmodics can be weaned, one drug at a time beginning with oral baclofen after ITB begins. Assessment should occur within 24 hours of a dose change. For adults, daily dose increases may be 5% to 15% once every 24 hours for cerebral-origin spasticity and 10% to 30% once every 24 hours for spinal-origin spasticity. Daily dose increases can be 5% to 15% once every 24 hours for children. Inpatients should be assessed at least every 24 hours and receive rehabilitation. Step dosing can be used for outpatients who cannot return daily. Dosing options include simple continuous dosing, variable 24-hour flex dosing, or regularly scheduled boluses. Patients/caregivers should understand the care plan, responsibilities, and possible side-effects. Low-reservoir alarm dates and refill schedules should be written down, along with emergency contact information. A higher concentration at refill can extend refill intervals, and a bridge bolus must be programmed. Time changes may affect flex dosing. Pump replacement should be scheduled at least three months in advance. CONCLUSIONS: ITB dosing is multistep and individualized.

Factors influencing health behaviors among active duty Air Force personnel.

BACKGROUND: Individual health behaviors affect whether U.S. Air Force (USAF) service members are fit and ready to deploy. PURPOSE: The purpose of this study was to understand health behaviors of USAF members to guide future interventions to reduce cardiovascular risks. METHODS: A qualitative descriptive study was conducted with a purposive sample of 24 active duty USAF participants. Conventional content analysis was used to derive data-driven themes that were compared with the Health Promotion Model (HPM). DISCUSSION: Participants defined health in a multifactorial way that covered physical, emotional, and spiritual dimensions. The three themes that contributed to participants' health behaviors addressed: "who I am," "what works for me," and the USAF culture. There was a poor fit between findings as expressed by these participants and the HPM. CONCLUSION: Although these findings were derived from a sample of USAF participants, the findings have implications for members of other military services. The findings also have relevance for nurses and other providers within the civilian work environments who can promote health and wellness by integrating a client's personal history into a plan for developing and sustaining a healthy lifestyle.

Online Focus Groups with Parents And Adolescents with Heart Transplants: Challenges and Opportunities.

Pediatric heart transplant recipients are scarce and widely dispersed. Previous studies of adolescents in this population were limited to small homogenous samples. Although online focus groups are an emerging data collection method, its use in pediatric populations has not been fully realized. The purpose of this study was to explore the feasibility of using online focus groups with pediatric populations. Adolescents (aged 13 to 21 years) at least 6 months post-heart transplant and their parents were recruited from two children's hospitals. An online discussion forum (iTracks) was used to conduct asynchronous focus groups with separate parent and adolescent groups. Six parents and four adolescents participated in the discussions. iTracks provided a framework for conducting focus groups in dispersed populations. Access to the discussion transcripts enhanced data analysis and eliminated transcription costs. Overall, online discussion forums were a feasible and cost-effective option to conduct online focus groups in this pediatric population.

Beyond emergency surgery: redefining acute care surgery.

BACKGROUND: Considerable debate exists regarding the definition, skill set, and training requirements for the new specialty of acute care surgery (ACS). We hypothesized that a patient subset could be identified that requires a level of care beyond general surgical training and justifies creation of this new specialty. MATERIALS AND METHODS: Reviewed patient admissions over 1-y to the only general surgical service at a level I trauma center-staffed by trauma and/or critical care trained physicians. Patients classified as follows: trauma, ACS, emergency general (EGS), or elective surgery. ACS patients are nonelective, nontrauma patients with significantly altered physiology requiring intensive care unit admission and/or specific complex operative interventions. Differences in demographics, hospital course, and outcomes were analyzed. RESULTS: In-patient service evaluated approximately 5500 patients, including 3300 trauma patients. A total of 2152 admissions include 37% trauma, 30% elective, 28% EGS, and 4% ACS. ACS and trauma patients were more likely to require multiple operations (ACS relative risk [RR] = 11.5; trauma RR = 5.7, P < 0.0001), have longer hospital and intensive care unit length of stay, and higher mortality (P < 0.0001). They were less likely to be discharged home (ACS RR = 0.75; trauma RR = 0.67, P < 0.0001) compared with that of the EGS group. EGS and elective patients were most similar to each other in multiple areas. CONCLUSIONS: ACS and EGS patients represent distinct patient cohorts, as reflected by significant differences in critical care needs, likelihood of multiple operations, and need for postdischarge rehabilitation. The skills required to care for ACS patients, including ability to rescue from complications and provide critical care, differ from those required for EGS patients and supports development of ACS training and regionalization of care.

The natural history and effect of resuscitation ratio on coagulation after trauma: a prospective cohort study.

OBJECTIVE: To investigate the natural history of coagulation factor perturbation after injury and identify longitudinal differences in clotting factor repletion by red blood cell:fresh frozen plasma (RBC:FFP) transfusion ratio. BACKGROUND: Hemostatic transfusion ratios of RBC to FFP approaching 1:1 are associated with a survival advantage in traumatic hemorrhage, even in patients with normal coagulation studies. METHODS: Plasma was prospectively collected from 336 trauma patients during their intensive care unit stay for up to 72 hours from February, 2005, to October, 2011. Standard coagulation studies as well as pro- and anticoagulant clotting factors were measured. RBC:FFP transfusion ratios were calculated at 6 hours after arrival and dichotomized into "low ratio" (RBC:FFP ≤ 1.5:1) and "high ratio" (RBC:FFP > 1.5:1) groups. RESULTS: Factor-level measurements from 193 nontransfused patients provide an early natural history of clotting factor-level changes after injury. In comparison, 143 transfused patients had more severe injury, prolonged prothrombin time and partial thromboplastin time (PTT), and lower levels of both pro- and anticoagulants up to 24 hours. PTT was prolonged up to 12 hours and only returned to admission baseline at 48 hours in "high ratio" patients versus correction by 6 hours in "low ratio" patients. Better repletion of factors V, VIII, and IX was seen longitudinally, and both unadjusted and injury-adjusted survival was significantly improved in "low ratio" versus "high ratio" groups. CONCLUSIONS: Resuscitation with a "low ratio" of RBC:FFP leads to earlier correction of coagulopathy, and earlier and prolonged repletion of some but not all procoagulant factors. This prospective evidence suggests hemostatic resuscitation as an interim standard of care for transfusion in critically injured patients pending the results of ongoing randomized study.

Group-based activities with on-site childcare and online support improve glucose tolerance in women within 5 years of gestational diabetes pregnancy.

BACKGROUND: Women with gestational diabetes history are at increased risk for type 2 diabetes. They face specific challenges for behavioural changes, including childcare responsibilities. The aim of this study is to test a tailored type 2 diabetes prevention intervention in women within 5 years of a pregnancy with gestational diabetes, in terms of effects on weight and cardiometabolic risk factors. METHODS: The 13-week intervention, designed based on focus group discussions, included four group sessions, two with spousal participation and all with on-site childcare. Web/telephone-based support was provided between sessions. We computed mean percentage change from baseline (95% confidence intervals, CI) for anthropometric measures, glucose tolerance (75 g Oral glucose tolerance test), insulin resistance/sensitivity, blood pressure, physical activity, dietary intake, and other cardiometabolic risk factors. RESULTS: Among the 36 enrolled, 27 completed final evaluations. Most attended ≥ 3 sessions (74%), used on-site childcare (88%), and logged onto the website (85%). Steps/day (733 steps, 95% CI 85, 1391) and fruit/vegetable intake (1.5 servings/day, 95% CI 0.3, 2.8) increased. Proportions decreased for convenience meal consumption (-30%, 95% CI -50, -9) and eating out (-22%, 95% CI -44, -0) ≥ 3 times/month. Body mass index and body composition were unchanged. Fasting (-4.9%, 95% CI -9.5, -0.3) and 2-hour postchallenge (-8.0%, 95% CI -15.6, -0.5) glucose declined. Insulin sensitivity increased (ISI 0,120 23.7%, 95% CI 9.1, 38.4; Matsuda index 37.5%, 95% CI 3.5, 72.4). Insulin resistance (HOMA-IR -9.4%, 95% CI -18.6, -0.1) and systolic blood pressure (-3.3%, 95% CI -5.8, -0.8) decreased. CONCLUSIONS: A tailored group intervention appears to lead to improvements in health behaviours and cardiometabolic risk factors despite unchanged body mass index and body composition. This approach merits further study. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01814995).

Structural brain alterations in children an average of 5 years after surgery and chemotherapy for brain tumors.

Young children with brain tumors are often treated with high-dose chemotherapy after surgery to avoid brain tissue injury associated with irradiation. The effects of systemic chemotherapy on healthy brain tissue in this population, however, are unclear. Our objective was to compare gray and white matter integrity using MRI procedures in children with brain tumors (n = 7, mean age 8.3 years), treated with surgery and high-dose chemotherapy followed by autologous hematopoietic cell rescue (AuHCR) an average of 5.4 years earlier, to age- and gender-matched healthy controls (n = 9, mean age 9.3 years). Diffusion tensor imaging data were collected to evaluate tissue integrity throughout the brain, as measured by mean diffusivity (MD), a marker of glial, neuronal, and axonal status, and fractional anisotropy (FA), an index of axonal health. Individual MD and FA maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance, with age and sex as covariates. Higher MD values, indicative of injury, emerged in patients compared with controls (p < .05, corrected for multiple comparisons), and were especially apparent in the central thalamus, external capsule, putamen, globus pallidus and pons. Reduced FA values in some regions did not reach significance after correction for multiple comparisons. Children treated with surgery and high-dose chemotherapy with AuHCR for brain tumors an average of 5.4 years earlier show alterations in white and gray matter in multiple brain areas distant from the tumor site, raising the possibility for long-term consequences of the tumor or treatment.

Transition to self-management after pediatric heart transplant.

CONTEXT: Little is known about adolescent transition to self-management after heart transplant. This gap in knowledge is critically important because the consequences of poor self-management are costly and life-threatening, often resulting in nonadherence, rejection, repeated hospitalizations, and poor quality of life. OBJECTIVE: To explore how adolescents and parents perceive their roles in self-management, and how adolescents integrate self-management into their daily lives and navigate the transition from parent-dominated to self-management. DESIGN: Qualitative descriptive design, using online focus groups. SETTING: Online focus groups using itracks, an online qualitative software program. PARTICIPANTS: A purposive sample of 4 adolescents, 13 to 21 years old, who were at least 6 months posttransplant, and of 6 parents of adolescent heart transplant recipients. RESULTS: Several parallel themes emerged from the parent and adolescent online focus groups. Managing medications was the predominant theme for both parents and adolescents. For the remaining themes, parents and adolescents expressed similar ideas that were categorized into parallel themes, which included staying on top of things/becoming independent, letting them be normal/being normal, and worries and stressors. CONCLUSIONS: The transition to self-management after heart transplant was a clear goal for both parents and adolescents. The transition is a shared responsibility between parents and adolescents with a gradual shift from parent-directed to self-management. The process of transition was not linear or smooth, and in several instances, parents described efforts to transfer responsibility to the adolescent only to take it back when complications arose. Additional research with a larger sample is needed in order to fully understand adolescent heart transplant recipients' transition to self-management.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target.

Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP.

Ras/MAPK signaling is often aberrantly activated in human cancers. The downstream effectors are transcription factors, including those encoded by the ETS gene family. Using cell-based assays and biophysical measurements, we have determined the mechanism by which Ras/MAPK signaling affects the function of Ets1 via phosphorylation of Thr38 and Ser41. These ERK2 phosphoacceptors lie within the unstructured N-terminal region of Ets1, immediately adjacent to the PNT domain. NMR spectroscopic analyses demonstrated that the PNT domain is a four-helix bundle (H2-H5), resembling the SAM domain, appended with two additional helices (H0-H1). Phosphorylation shifted a conformational equilibrium, displacing the dynamic helix H0 from the core bundle. The affinity of Ets1 for the TAZ1 (or CH1) domain of the coactivator CBP was enhanced 34-fold by phosphorylation, and this binding was sensitive to ionic strength. NMR-monitored titration experiments mapped the interaction surfaces of the TAZ1 domain and Ets1, the latter encompassing both the phosphoacceptors and PNT domain. Charge complementarity of these surfaces indicate that electrostatic forces act in concert with a conformational equilibrium to mediate phosphorylation effects. We conclude that the dynamic helical elements of Ets1, appended to a conserved structural core, constitute a phospho-switch that directs Ras/MAPK signaling to downstream changes in gene expression. This detailed structural and mechanistic information will guide strategies for targeting ETS proteins in human disease.