Stereotactic Radiosurgery Practice Patterns for Brain Metastases in the United States: A National Survey

Background: Stereotactic radiosurgery (SRS) has emerged as an important modality for the treatment of intracranial metastases. There are currently few established guidelines delineating indications for SRS use and fewer still regarding plan evaluation in the treat- ment of multiple brain metastases. Methods: An 18 question electronic survey was distributed to radiation oncologists at National Cancer Institute (NCI) designated cancer centers in the US (60). Centers without radiation oncologists were excluded. Physicians who indicated that they do not prescribe SRS were excluded from the remaining survey questions. Sign test and Chi-square test were used to determine if responses differed significantly from random distribution. Results: 116 of the 697 radiation oncologists surveyed completed the questionnaire, representing 51 institutions. 62% reported treating patients with brain metastases using SRS. Radiation oncologists prescribing SRS most commonly treat CNS (66.2%) and lung (49.3%) malignancies. SRS was used more frequently for \u3c10 brain metastases (73.7%; p\u3c.0001) and whole brain radiation therapy (WBRT) for \u3e10 brain metastases (82.5%; p\u3c.0001). The maximum number of lesions physicians were willing to treat with SRS without WBRT was 1-4 (40.4%) and 5-10 (42.4%) (p\u3c.0001 compared to 11-15, 16-20 and no limit). The most important criteria for choosing SRS or WBRT were number of lesions (p\u3c.0001) and performance status (p=.016). The most common margin for SRS was 0 mm (49.1%; p=.0021). The most common dose constraints other than critical structure was conformity index (84.2%) and brain V12 (61.4%). The LINAC was the most common treatment modality (54.4%) and mono-isocenter technique for multiple brain metastases was commonly used (43.9%; p=.23). Most departments do not have a policy for brain metastases treatment (64.9%; p=.024). Conclusions: This is one of the first national surveys assessing the use of SRS for brain metastases in clinical practice. These data highlight some clinical considerations for physicians treating brain metastases with SRS. Summary: This is among the first national surveys to assess the use of SRS for brain metastases in clinical practice. Specifically, radiation oncologist reported increasingly using SRS instead of WBRT for treating \u3c10 metastases, with the LINAC being the most common modality. Further, treatment parameters considered the most important included 0 mm margins, conformity index, brain V12, and mono- isocenter technique for multiple brain metastases. These results may provide context regarding the use of SRS for brain metastases in clinical practice

Subcritical CO2 Sintering of Microspheres of Different Polymeric Materials to Fabricate Scaffolds for Tissue Engineering

The aim of this study was to use CO2 at sub-critical pressures as a tool to sinter 3D, macroporous, microsphere-based scaffolds for bone and cartilage Tissue Engineering Porous scaffolds composed of ~200 µm microspheres of either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) were prepared using dense phase CO2 sintering, which were seeded with rat bone marrow mesenchymal stromal cells (rBMSCs), and exposed to either osteogenic (PLGA, PCL) or chondrogenic (PLGA) conditions for 6 weeks. Under osteogenic conditions, the PLGA constructs produced over an order of magnitude more calcium than the PCL constructs, whereas the PCL constructs had far superior mechanical and structural integrity (125 times stiffer than PLGA constructs) at week 6, along with twice the cell content of the PLGA constructs. Chondrogenic cell performance was limited in PLGA constructs, perhaps as a result of the polymer degradation rate being too high. The current study represents the first long-term culture of CO2-sintered microsphere-based scaffolds, and has established important thermodynamic differences in sintering between the selected formulations of PLGA and PCL, with the former requiring adjustment of pressure only, and the latter requiring the adjustment of both pressure and temperature. Based on more straightforward sintering conditions and more favorable cell performance, PLGA may be the material of choice for microspheres in a CO2 sintering application, although a different PLGA formulation with the encapsulation of growth factors, extracellular matrix-derived nanoparticles, and/or buffers in the microspheres may be advantageous for achieving a more superior cell performance than observed here

Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States

Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States.BackgroundIt is hypothesized, but not proven, that peritoneal dialysis might be the optimal treatment for end-stage renal disease (ESRD) patients with established congestive heart failure (CHF) through better volume regulation compared with hemodialysis.MethodsNational incidence data on 107,922 new ESRD patients from the Center for Medicare and Medicaid Services (CMS) Medical Evidence Form were used to test the hypothesis that peritoneal dialysis was superior to hemodialysis in prolonging survival of patients with CHF. Nonproportional Cox regression models evaluated the relative hazard of death for patients with and without CHF by dialysis modality using primarily the intent-to-treat but also the as-treated approach. Diabetics and nondiabetics were analyzed separately.ResultsThe overall prevalence of CHF was 33% at ESRD initiation. There were 27,149 deaths (25.2%), 5423 transplants (5%), and 3753 (3.5%) patients lost to follow-up over 2years. Adjusted mortality risks were significantly higher for patients with CHF treated with peritoneal dialysis than hemodialysis [diabetics, relative risk (RR) = 1.30, 95% confidence interval (CI) 1.20 to 1.41; nondiabetics, RR = 1.24, 95% CI 1.14 to 1.35]. Among patients without CHF, adjusted mortality risk were higher only for diabetic patients treated with peritoneal dialysis compared with hemodialysis (RR = 1.11, 95% CI 1.02 to 1.21) while nondiabetics had similar survival on peritoneal dialysis or hemodialysis (RR = 0.97, 95% CI 0.91 to 1.04).ConclusionNew ESRD patients with a clinical history of CHF experienced poorer survival when treated with peritoneal dialysis compared with hemodialysis. These data suggest that peritoneal dialysis may not be the optimal choice for new ESRD patients with CHF perhaps through impaired volume regulation and worsening cardiomyopathy

Tailoring of processing parameters for sintering microsphere-based scaffolds with dense phase carbon dioxide

Jeon, J. H., Bhamidipati, M., Sridharan, B., Scurto, A. M., Berkland, C. J. and Detamore, M. S. (2013), Tailoring of processing parameters for sintering microsphere-based scaffolds with dense-phase carbon dioxide. J. Biomed. Mater. Res., 101B: 330–337. doi:10.1002/jbm.b.32843Microsphere-based polymeric tissue-engineered scaffolds offer the advantage of shape-specific constructs with excellent spatiotemporal control and interconnected porous structures. The use of these highly versatile scaffolds requires a method to sinter the discrete microspheres together into a cohesive network, typically with the use of heat or organic solvents. We previously introduced subcritical CO2 as a sintering method for microsphere-based scaffolds; here we further explored the effect of processing parameters. Gaseous or subcritical CO2 was used for making the scaffolds, and various pressures, ratios of lactic acid to glycolic acid in poly(lactic acid-co-glycolic acid), and amounts of NaCl particles were explored. By changing these parameters, scaffolds with different mechanical properties and morphologies were prepared. The preferred range of applied subcritical CO2 was 15–25 bar. Scaffolds prepared at 25 bar with lower lactic acid ratios and without NaCl particles had a higher stiffness, while the constructs made at 15 bar, lower glycolic acid content, and with salt granules had lower elastic moduli. Human umbilical cord mesenchymal stromal cells (hUCMSCs) seeded on the scaffolds demonstrated that cells penetrate the scaffolds and remain viable. Overall, the study demonstrated the dependence of the optimal CO2 sintering parameters on the polymer and conditions, and identified desirable CO2 processing parameters to employ in the sintering of microsphere-based scaffolds as a more benign alternative to heat-sintering or solvent-based sintering methods

Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment

Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity. Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment

D-branes in PP-wave light cone string field theory

The cubic interaction vertex and the dynamical supercharges are constructed for open strings ending on D7-branes, in light-cone superstring field theory in PP-wave background. In this context, we write down the symmetry generators in terms of the relevant group structure: SU(2) x SU(2) x SO(2) x SO(2), originating from the eight transverse directions in the PP-wave background and use the expressions to explicitly construct the vertex at the level of stringy zero modes. The results are further generalized to include all the stringy excitations as well.Comment: 30 pages, correction in eqn. (4.28), few equations (appendix), Comments (p.17-18) and a reference (no. 58) added, typo is corrected in eqn. (4.5

The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation.This work was undertaken as a contribution to the Rapid Assistance in Modelling the Pandemic (RAMP) initiative, coordinated by the Royal Society