Plan Quality and Treatment Efficiency for Radiosurgery to Multiple Brain Metastases: Non-Coplanar RapidArc vs. Gamma Knife.

OBJECTIVES: This study compares the dosimetry and efficiency of two modern radiosurgery [stereotactic radiosurgery (SRS)] modalities for multiple brain metastases [Gamma Knife (GK) and LINAC-based RapidArc/volumetric modulated arc therapy], with a special focus on the comparison of low-dose spread. METHODS: Six patients with three or four small brain metastases were used in this study. The size of targets varied from 0.1 to 10.5 cc. SRS doses were prescribed according to the size of lesions. SRS plans were made using both Gamma Knife(®) Perfexion and a single-isocenter, multiple non-coplanar RapidArc(®). Dosimetric parameters analyzed included RTOG conformity index (CI), gradient index (GI), 12 Gy isodose volume (V 12Gy) for each target, and the dose spread (Dspread) for each plan. Dspread reflects SRS plan\u27s capability of confining radiation to within the local vicinity of the lesion and to not spread out to the surrounding normal brain tissues. Each plan has a dose (Dspread), such that once dose decreases below Dspread (on total tissue dose-volume histogram), isodose volume starts increasing dramatically. Dspread is defined as that dose when volume increase first exceeds 20 cc/0.1 Gy dose decrease. RESULTS: RapidArc SRS has smaller CI (1.19 ± 0.14 vs. 1.50 ± 0.16, p \u3c 0.001) and larger GI (4.77 ± 1.49 vs. 3.65 ± 0.98, p \u3c 0.01). V 12Gy results were comparable (2.73 ± 1.38 vs. 3.06 ± 2.20 cc, p = 0.58). Moderate to lower dose spread, V6, V4.5, and V3, were also equivalent. GK plans achieved better very low-dose spread (≤3 Gy) and also had slightly smaller Dspread, 1.9 vs. 2.5 Gy. Total treatment time for GK is estimated between 60 and 100 min. GK treatments are between 3 and 5 times longer compared to RapidArc treatment techniques. CONCLUSION: Dosimetric parameters reflecting prescription dose conformality (CI), dose fall off (GI), radiation necrosis indicator (V 12Gy), and dose spread (Dspread) were compared between GK SRS and RapidArc SRS for multi-mets. RapidArc plans have smaller CI but larger GI. V 12Gy are comparable. GK appears better at reducing only very low-dose spread (\u3c3 \u3eGy). The treatment time of RapidArc SRS is significantly reduced compared to GK SRS

Working sandwich generation women utilize strategies within and between roles to achieve role balance

Increasingly, women simultaneously balance the roles of mother, parental carer and worker. However, individual role balance strategies among these working \u27sandwich\u27 generation women have not been thoroughly explored. Eighteen women combining these three roles were interviewed about their individual role balance strategies. Findings were identified through the framework analysis technique, underpinned by the Model of Juggling Occupations. Achieving and maintaining role balance was explained as a complex process accomplished through a range of strategies. Findings revealed the women used six within-role balance strategies: living with integrity, being the best you can, doing what you love, loving what you do, remembering why and searching for signs of success. The women also described six between-role balance strategies: maintaining health and wellbeing, repressing perfectionism, managing time and energy, releasing responsibility, nurturing social connection and reciprocating. These findings provide a basis for health care providers to understand and potentially support working \u27sandwich\u27 generation women. © 2016 Evans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

What Happens When you Ask for Feedback? Anticipating and Addressing Challenges Can Be Effective for Eliciting Parents' Views About Their Critically Ill Child's Retrieval to Paediatric Intensive Care.

User feedback is an important element of health-service evaluation and can be used to improve services but can be difficult to obtain, particularly in acute care situations. As part of a national study, we explored stakeholders' perspectives on paediatric critical care retrieval processes through questionnaires and interviews. Obtaining feedback in a highly charged, stressful and busy paediatric intensive care unit (PICU) environment is fraught with difficulties so we aimed to optimise each stage of data collection by being both proactive and reactive. Patient and public involvement occurred throughout and engagement with sites and supporting local research staff to approach and recruit families were prioritised. High-quality study materials were developed to reduce local staff burden and promote and maintain study awareness. We describe strategies used and what worked/did not work. We suggest approaches for optimising elicitation of parents' experiences in difficult circumstances, highlighting the importance of engagement and commitment of PICU staff

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Rhinovirus illnesses during infancy predict subsequent childhood wheezing

Background: The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/ or allergic diseases in early childhood is not established. Objective: To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. Methods: By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Results: Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR] 5 2.1), older siblings (OR 5 2.5), allergic sensitization to foods at age 1 year (OR 5 2.0), any moderate to severe respiratory illness without wheezing during infancy (OR 5 3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR 5 3.0), rhinovirus (OR 5 10) and/or non-rhinovirus/RSV pathogens (OR 5 3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR 5 6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR 5 6.6; P < .0001). Conclusion: In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature. (J Allergy Clin Immunol 2005;116:571-7.

A Comparative Analysis of Anterior & Lateral Cranial Base CSF Leaks

Introduction The optimal strategy for management of Idiopathic Intracranial Hypertension (IIH) in anterior and lateral cranial base meningoencephaloceles remains debated. The purpose of this study is to present a comparison of the surgical management of anterior and lateral cranial base meningoencephalocele and a treatment algorithm for the diagnosis and management of IIH in this patient population. Methods Retrospective study of 109 patients who underwent anterior or lateral CSF leak repair at TJU from 2004-2020. Epic & RedCap were utilized to record data. Patient demographics, presenting symptoms, imaging, Beta-2 Transferring testing, surgery, repair, and post-op data were collected. Two-sided Chi-squared tests and Independent t-test were performed via SPSS Statistics 26. Results 49 anterior cranial base (ACB) and 60 lateral cranial base (LCB) defects were included. Anterior cohort had significantly more women (N=77, 85.7%, p=0.02). Anterior cohort presented with significantly higher multiple leak sites (24.5% vs 15.0%, p=0.036). Six patients, 3 in each cohort, none of whom received Ventriculoperitoneal shunts (VPS) developed recurrence. VPS were placed for long-term CSF diversion in 23 ACB cases (46.9%) and 10 LCB cases (16.7%), (p\u3c0.01). Discussion ACB cases had a higher incidence of females, multiple site leaks, and more likely to undergo VPS placement. No patients developed recurrence after placement of a VPS. Long-term CSF diversion via VPS, in addition to surgical repair, should be considered in patients with elevated intracranial pressure and other high-risk factors to prevent recurrence of CSF leaks

Fractional exhaled nitric oxide measurements are most closely associated with allergic sensitization in school-age children

Background: Factors affecting fractional exhaled nitric oxide (FeNO) in early childhood are incompletely understood. Objective: To examine the relationships between FeNO and allergic sensitization, total IgE, atopic dermatitis, rhinitis, asthma, and lung function (spirometry) in children. Methods: Children at high risk of asthma and other allergic diseases because of parental history were enrolled at birth and followed prospectively. FeNO was measured by an online technique at ages 6 and 8 years. Relationships among FeNO, various atopic characteristics, and asthma were evaluated. Results: Reproducible FeNO measurements were obtained in 64% (135/210) of 6-year-old and 93% (180/194) of 8-year-old children. There was seasonal variability in FeNO. Children with aeroallergen sensitization at ages 6 and 8 years had increased levels of FeNO compared with those not sensitized (geometric mean; 6 years, 10.9 vs 6.7 parts per billion [ppb], P < .0001; 8 years, 14.6 vs 7.1 ppb, P < .0001). FeNO was higher in children with asthma than in those without asthma at 8 years but not 6 years of age (6 years, 9.2 vs 8.3 ppb, P 5 .48; 8 years, 11.5 vs 9.2 ppb, P 5 .03). At 8 years of age, this difference was no longer significant in a multivariate model that included aeroallerge