Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review

Objective The objective of this study was to investigate outcomes for patients with brainstem metastases treated with stereotactic radiosurgery (SRS). Methods Patients with brainstem metastases treated with SRS between April 2006 and June 2012 were identified from a prospective database. Patient and treatment-related factors were recorded. Kaplan-Meier analysis was used to calculate survival and freedom from local and distant brain progression. Univariate and multivariate Cox regression was used to identify factors important for overall survival. Results In total, 44 patients received SRS for 48 brainstem metastases of whom 33 (75 %) also received whole brain radiotherapy (WBRT): 23 patients (52 %) WBRT prior to SRS, 6 (13.6 %) WBRT concurrently with SRS and 4 (9.0 %) WBRT after SRS. Eight patients received a second course ofWBRTat further progression. Median target volume was 1.33 cc (range 0.04–12.17) and median prescribed marginal dose was 15 Gy (range 10–22). There were four cases of local failure, and 6-month and 1-year freedom from local failure was 84.6 and 76.9 %, respectively. Median overall survival (OS) was 5.4 months. There were four cases of radionecrosis, 2 (4.8 %) of which were symptomatic. The absence of external beam brain radiotherapy (predominantly WBRT) showed a trend towards improved OS on univariate analysis. Neither local nor distant brain failure significantly impacted OS. Conclusion This retrospective series of patients treated with SRS for brainstem metastases, largely in combination with at least one course of WBRT, demonstrates that this approach is safe and results in good local control. In this cohort, no variables significantly impacted OS, including intracranial control

Enhancing the health of women living with HIV: the SMART/EST Women’s Project

The principal objective of these multisite studies (Florida, New York, New Jersey: epicenters for human immunodeficiency virus [HIV] among women) was to develop and implement effective combinations of behavioral interventions to optimize the health status of the most neglected and understudied population affected by the acquired immunodeficiency syndrome (AIDS) epidemic in the United States: poor women of color living with HIV. The two studies enrolled nearly 900 women randomly assigned to “high intensity” (cognitive–behavioral stress management training combined with expressive–supportive therapy [CBSM]+ group) or “low intensity” (individual psychoeducational program) treatment conditions over a period of 9 years. The initial study of the stress management and relaxation training/expressive–supportive therapy (SMART/EST) Women’s Project (SWP I) focused on reducing depression and anxiety, as well as improving self-efficacy and overall quality of life for women with case-defined AIDS. Findings from this study demonstrated the utility of CBSM+ in reducing distress (depression, anxiety) and denial, while improving social support, self-efficacy, coping skills, and quality of life. The second study (SWP II), which included all women living with HIV, extended these findings by demonstrating that exposure to CBSM+ significantly improved the ability of the participants to take advantage of a health behavior change program encouraging the adoption and maintenance of healthier lifestyle behaviors (high levels of medication adherence, appropriate nutritional intake and physical activity, safer sexual practices, and reduced alcohol use/abuse) essential for optimal health in the context of living with HIV. SWP II also determined that the intervention program was equally beneficial to less-acculturated segments of the affected population (ie, non-English speaking HIV+ women) through the creation of culturally and linguistically sensitive Spanish and Creole versions of the program. A third study (SWP III) is currently underway to “translate” this evidence-based treatment program into Community Health Centers in Miami, New York City, and metropolitan New Jersey

Craniospinal irradiation as part of re-irradiation for children with recurrent intracranial ependymoma

Background: The goal of this study was to evaluate outcomes in children with relapsed, molecularly characterized intracranial ependymoma treated with or without craniospinal irradiation (CSI) as part of a course of repeat radiation therapy (re-RT). Methods: This was a retrospective cohort study of 31 children. Patients with distant relapse received CSI as part of re-RT. For patients with locally recurrent ependymoma, those treated before 2012 were re-irradiated with focal re-RT. In 2012, institutional practice changed to offer CSI, followed by boost re-RT to the site of resected or gross disease. Results: Median follow-up was 5.5 years. Of 9 patients with distant relapse after initial RT, 2-year freedom from progression (FFP) and overall survival (OS) were 12.5% and 62.5%, respectively. There were 22 patients with local failure after initial RT. In these patients, use of CSI during re-RT was associated with improvement in 5-year FFP (83.3% with CSI vs 15.2% with focal re-RT only, P = 0.030). In the subgroup of patients with infratentorial primary disease, CSI during re-RT also improved 5-year FFP (100% with CSI, 10.0% with focal re-RT only, P = 0.036). Twenty-three patients had known molecular status; all had posterior fossa group A tumors (n = 17) or tumors with a RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) fusion (n = 6). No patient developed radiation necrosis after fractionated re-RT, though almost all survivors required assistance throughout formal schooling. Five out of 10 long-term survivors have not developed neuroendocrine deficits. Conclusions: Re-irradiation with CSI is a safe and effective treatment for children with locally recurrent ependymoma and improves disease control compared with focal re-irradiation, with the benefit most apparent for those with infratentorial primary tumors

Gliosarcoma: a study of four cases

Gliosarcomas (GS) are highly malignant and rare tumors of the central nervous system with a poor prognosis. We report here on four patients with GS, the median survival for whom was 9.25 months. Prognosis of GS remains poor, and a multidisciplinary approach (surgery, radiation therapy, and chemotherapy) seems to be associated with slightly more prolonged survival times

A dimensioning and tolerancing methodology for concurrent engineering applications I: problem representation

This paper is the first of two which present a methodology for determining the dimensional specifications of all the component parts and sub-assemblies of a product according to their dimensional requirements. To achieve this goal, two major steps are followed, each of which is described in a paper. In the first paper, all relationships necessary for finding the values of dimensions and tolerances are represented in a matrix form, known as a Dimensional Requirements/Dimensions (DR/D) matrix. In the second paper, the values of individual dimensions and tolerances are determined by applying a comprehensive solution strategy to satisfy all the relationships represented in the DR/D matrix. The methodology is interactive and suitable for use in a concurrent engineering (CE) environment. The graphical tool presented in this paper will assist a CE team in visualizing the overall D&T problem and foreseeing the ramifications of decisions regarding the selection of dimensions and tolerances. This will assist the CE team to systematically determine all the controllable variables, such as dimensions, tolerances, and manufacturing processes

The appropriateness of gatekeeping in the provision of reproductive health care for adolescents in Lithuania:the general practice perspective

BACKGROUND: Adolescents' consultation of primary health care services remains problematic despite their accessibility. The reproductive health service seeking behavior of adolescents is the object of much research but little is known about how this behavior is influenced by the gatekeeping system. This study aimed to explore general practitioners' perceptions of the appropriateness of gatekeeping in adolescent reproductive health care. METHODS: Twenty in-depth interviews regarding factors affecting adolescent reproductive health care were carried out on a diverse sample of general practitioners and analyzed using grounded theory. RESULTS: The analysis identified several factors that shaped GPs' negative attitude to gatekeeping in adolescent reproductive health care. Its appropriateness in this field was questionable due to a lack of willingness on the part of GPs to provide reproductive health services for teenagers, their insufficient training, inadequately equipped surgeries and low perceived support for reproductive health service provision. CONCLUSION: Since factors for improving adolescent reproductive health concern not only physicians but also the health system and policy levels, complex measures should be designed to overcome these barriers. Discussion of a flexible model of gatekeeping, encompassing both co-ordination of care provided by GPs and the possibility of patients' self-referral, should be included in the political agenda. Adolescents tend to under-use rather than over-use reproductive health services and every effort should be made to facilitate the accessibility of such services

Impaired immune function in Gulf War Illness

<p>Abstract</p> <p>Background</p> <p>Gulf War Illness (GWI) remains a serious health consequence for at least 11,000 veterans of the first Gulf War in the early 1990s. Our understanding of the health consequences that resulted remains inadequate, and this is of great concern with another deployment to the same theater of operations occurring now. Chronic immune cell dysfunction and activation have been demonstrated in patients with GWI, although the literature is not uniform. We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling.</p> <p>Methods</p> <p>This pilot study enrolled 9 GWI cases identified from the Department of Veterans Affairs GWI registry, and 11 sedentary control veterans who had not been deployed to the Persian Gulf and were matched to cases by sex, body mass index (BMI) and age. We measured peripheral blood cell numbers, NK cytotoxicity, cytokines and expression levels of 20,000 genes immediately before, immediately after and 4 hours following a standard bicycle ergometer exercise challenge.</p> <p>Results</p> <p>A repeated-measures analysis of variance revealed statistically significant differences for three NK cell subsets and NK cytotoxicity between cases and controls (p < 0.05). Linear regression analysis correlating NK cell numbers to the gene expression profiles showed high correlation of genes associated with NK cell function, serving as a biologic validation of both the <it>in vitro </it>assays and the microarray platform. Intracellular perforin levels in NK and CD8 T-cells trended lower and showed a flatter profile in GWI cases than controls, as did the expression levels of the perforin gene PRF1. Genes distinguishing cases from controls were associated with the glucocorticoid signaling pathway.</p> <p>Conclusion</p> <p>GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. Pro-inflammatory cytokines, T-cell ratios, and dysregulated mediators of the stress response (including salivary cortisol) were also altered in GWI cases compared to control subjects. An interesting and potentially important observation was that the exercise challenge augments these differences, with the most significant effects observed immediately after the stressor, possibly implicating some block in the NK and CD8 T-cells ability to respond to "stress-mediated activation". This has positive implications for the development of laboratory diagnostic tests for this syndrome and provides a paradigm for exploration of the immuno-physiological mechanisms that are operating in GWI, and similar complex syndromes. Our results do not necessarily elucidate the cause of GWI, but they do reveal a role for immune cell dysfunction in sustaining illness.</p