135 research outputs found
Integration of systemic therapy and stereotactic radiosurgery for brain metastases
Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis
Sensitivity Analysis of Ozone Formation and Transport for a Central California Air Pollution Episode
Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance
Background: Treatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the choice and efficacy of a selected targeted therapeutic, and hence the objective of this study was to analyze discordance in EGFR status in patients with lung cancer brain metastasis (LCBM). Methods: Using PRISMA guidelines, a systematic review was performed of series in the Medline database of biopsied or resected LCBM published before May, 2020. Key words included âlung cancerâ and âbrain metastasisâ combined with âepidermal growth factor receptor/EGFR,â and âreceptor conversion/discordance or concordance.â Weighted random effects models were used to calculate pooled estimates. Results: We identified 501 patients from 19 full-text articles for inclusion in this study. All patients underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. On primary/LCBM comparison, the weighted pooled estimate for overall EGFR receptor discordance was 10% (95% CI 5â17%). The weighted effects model estimated a gain of an EGFR mutation in a brain metastases in patients with negative primary tumors was 7% (95% CI 4â12%). Alternatively, the weighted effects model estimate of loss of an EGFR mutation in patients with detected mutations in the primary tumor was also 7% (95% CI 4â10%). KRAS testing was also performed on both primary tumors and LCBM in a subset of 148 patients. The weighted effects estimate of KRAS-mutation discordance among LCBM compared to primary tumors was 13% (95% CI 5â27%). The weighted effects estimated of KRAS gain and loss in LCBM was 10% (95% CI 6â18%) and 8% (95% CI 4â15%), respectively. Meta-regression analysis did not find any association with any factors that could be associated with discordances. Conclusions: EGFR and KRAS mutation status discordance between primary tumor and LCBM occurs in approximately 10% and 13% of patients, respectively. Evaluation of LCBM receptor status is key to biomarker-driven targeted therapy for intracranial disease and awareness of subtype switching is critical for those patients treated with systemic therapy alone for intracranial disease
Factors associated with unplanned readmissions and costs following resection of brain metastases in the United States
The purpose of this study was to critically analyze the risk of unplanned readmission following resection of brain metastasis and to identify key risk factors to allow for early intervention strategies in high-risk patients. We analyzed data from the Nationwide Readmissions Database (NRD) from 2010â2014, and included patients who underwent craniotomy for brain metastasis, identified using ICD-9-CM diagnosis (198.3) and procedure (01.59) codes. The primary outcome of the study was unplanned 30-day all-cause readmission rate. Secondary outcomes included reasons and costs of readmissions. Hierarchical logistic regression model was used to identify the factors associated with 30-day readmission following craniotomy for brain metastasis. During the study period, 44,846 index hospitalizations occurred for patients who underwent resection of brain metastasis. In this cohort, 17.8% (n = 7,965) had unplanned readmissions within the first 30 days after discharge from the index hospitalization. The readmission rate did not change significantly during the five-year study period (p-trend = 0.286). The median per-patient cost for 30-day unplanned readmission was 26.4 million per year, which extrapolates to a national expenditure of $269.6 million. Increasing age, male sex, insurance status, Elixhauser comorbidity index, length of stay, teaching status of the hospital, neurological complications and infectious complications were associated with 30-day readmission following discharge after an index admission for craniotomy for brain metastasis. Unplanned readmission rates after resection of brain metastasis remain high and involve substantial healthcare expenditures. Developing tools and interventions to prevent avoidable readmissions could focus on the high-risk patients as a future strategy to decrease substantial healthcare expense
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Sensitivity analysis of ozone formation and transport for a Central California air pollution episode
CMAQ-HDDM is used to determine spatial and temporal variations in ozone limiting reagents and local vs upwind source contributions for an air pollution episode in Central California. We developed a first- and second- order sensitivity analysis approach with the Decoupled Direct Method to examine spatial and temporal variations of ozone-limiting reagents and the importance of local vs upwind emission sources in the San Joaquin Valley of central California for a five-day ozone episode (29th July-3rd Aug, 2000). Despite considerable spatial variations, nitrogen oxides (NO{sub x}) emission reductions are overall more effective than volatile organic compound (VOC) control for attaining the 8-hr ozone standard in this region for this episode, in contrast to the VOC control that works better for attaining the prior 1-hr ozone standard. Inter-basin source contributions of NO{sub x} emissions are limited to the northern part of the SJV, while anthropogenic VOC (AVOC) emissions, especially those emitted at night, influence ozone formation in the SJV further downwind. Among model input parameters studied here, uncertainties in emissions of NO{sub x} and AVOC, and the rate coefficient of the OH + NO{sub 2} termination reaction, have the greatest effect on first-order ozone responses to changes in NO{sub x} emissions. Uncertainties in biogenic VOC emissions only have a modest effect because they are generally not collocated with anthropogenic sources in this region
Hospitalization rates from radiotherapy complications in the United States
Hospitalizations due to radiotherapy (RT) complications result in significant healthcare expenditures and adversely affect the quality of life of cancer patients. Using a nationally representative dataset, the objective of this study is to identify trends in the incidence of these hospitalizations, their causes, and the resulting financial burden. Data from the National Inpatient Sample was retrospectively analyzed from 2005 to 2016. RT complications were identified using ICD-9 and ICD-10 external cause-of-injury codes. The hospitalization rate was the primary endpoint, with cost and in-hospital death as secondary outcomes. 443,222,223 weighted hospitalizations occurred during the study period, of which 482,525 (0.11%) were attributed to RT. The 3 most common reasons for RT-related hospitalization were cystitis (4.8%, standard error [SE] = 0.09), gastroenteritis/colitis (3.7%, SE = 0.07), and esophagitis (3.5%, SE = 0.07). Aspiration pneumonitis (1.4-fold) and mucositis (1.3-fold) had the highest relative increases among these hospitalizations from 2005 to 2016, while esophagitis (0.58-fold) and disorders of the rectum and anus were the lowest (0.67-fold). The median length of stay of patient for hospitalization for RT complications was 4.1 (IQR, 2.2â7.5) days and the median charge per patient was 4.9 billion. Hospitalization for RT-related complications is relatively rare, but those that are admitted incur a substantial cost. Use of advanced RT techniques should be employed whenever possible to mitigate the risk of severe toxicity and therefore reduce the need to admit patients
Microservice Transition and its Granularity Problem: A Systematic Mapping Study
Microservices have gained wide recognition and acceptance in software
industries as an emerging architectural style for autonomic, scalable, and more
reliable computing. The transition to microservices has been highly motivated
by the need for better alignment of technical design decisions with improving
value potentials of architectures. Despite microservices' popularity, research
still lacks disciplined understanding of transition and consensus on the
principles and activities underlying "micro-ing" architectures. In this paper,
we report on a systematic mapping study that consolidates various views,
approaches and activities that commonly assist in the transition to
microservices. The study aims to provide a better understanding of the
transition; it also contributes a working definition of the transition and
technical activities underlying it. We term the transition and technical
activities leading to microservice architectures as microservitization. We then
shed light on a fundamental problem of microservitization: microservice
granularity and reasoning about its adaptation as first-class entities. This
study reviews state-of-the-art and -practice related to reasoning about
microservice granularity; it reviews modelling approaches, aspects considered,
guidelines and processes used to reason about microservice granularity. This
study identifies opportunities for future research and development related to
reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table
VOC reactivity in central California: comparing an air quality model to ground-based measurements
International audienceVolatile organic compound (VOC) reactivity in central California is examined using a photochemical air quality model (the Community Multiscale Air Quality model; CMAQ) and ground-based measurements to evaluate the contribution of VOC to photochemical activity. We classify VOC into four categories: anthropogenic, biogenic, aldehyde, and other oxygenated VOC. Anthropogenic and biogenic VOC consist of primary emissions, while aldehydes and other oxygenated VOC include both primary anthropogenic emissions and secondary products from primary VOC oxidation. To evaluate the model treatment of VOC chemistry, we compare calculated and modeled OH and VOC reactivities using the following metrics: 1) cumulative distribution functions of NO<sub>x</sub> concentration and VOC reactivity (R<sub>OH,VOC</sub>), 2) the relationship between R<sub>OH,VOC</sub> and NO<sub>x</sub>, 3) total OH reactivity (R<sub>OH,total</sub>) and speciated contributions, and 4) the relationship between speciated R<sub>OH,VOC</sub> and NO<sub>x</sub>. We find that the model predicts R<sub>OH,total</sub> to within 25?40% at three sites representing urban (Sacramento), suburban (Granite Bay) and rural (Blodgett Forest) chemistry. However in the urban area of Fresno, the model under predicts NO<sub>x</sub> and VOC emissions by a factor of 2?3. At all locations the model is consistent with observations of the relative contributions of total VOC. In urban areas, anthropogenic and biogenic R<sub>OH,VOC</sub> are predicted fairly well over a range of NO<sub>x</sub> conditions. In suburban and rural locations, anthropogenic and other oxygenated R<sub>OH,VOC</sub> relationships are reproduced, but calculated biogenic and aldehyde R<sub>OH,VOC</sub> are often poorly characterized by measurements, making evaluation of the model with available data unreliable. In central California, 30?50% of the modeled urban VOC reactivity is due to aldehydes and other oxygenated species, and the total oxygenated R<sub>OH,VOC</sub> is nearly equivalent to anthropogenic VOC reactivity. In rural vegetated regions, biogenic and aldehyde reactivity dominates. This indicates that more attention needs to be paid to the accuracy of models and measurements of both primary emissions of oxygenated VOC and secondary production of oxygenates, especially formaldehyde and other aldehydes, and that a more comprehensive set of oxygenated VOC measurements is required to include all of the important contributions to atmospheric reactivity
Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon
The transverse momentum and rapidity distributions of net protons and
negatively charged hadrons have been measured for minimum bias proton-nucleus
and deuteron-gold interactions, as well as central oxygen-gold and
sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net
protons at midrapidity in central nucleus-nucleus collisions increases both
with target mass for sulphur projectiles and with the projectile mass for a
gold target. The shape of the rapidity distributions of net protons forward of
midrapidity for d+Au and central S+Au collisions is similar. The average
rapidity loss is larger than 2 units of rapidity for reactions with the gold
target. The transverse momentum spectra of net protons for all reactions can be
described by a thermal distribution with `temperatures' between 145 +- 11 MeV
(p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The
multiplicity of negatively charged hadrons increases with the mass of the
colliding system. The shape of the transverse momentum spectra of negatively
charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and
central nucleus-nucleus collisions. The mean transverse momentum is almost
constant in the vicinity of midrapidity and shows little variation with the
target and projectile masses. The average number of produced negatively charged
hadrons per participant baryon increases slightly from p+p, p+A to central
S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.
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