Should a Sentinel Node Biopsy Be Performed in Patients with High-Risk Breast Cancer?

A negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded upfront exploration of the axilla or comprehensive axillary irradiation

Fast-ignition design transport studies: realistic electron source, integrated PIC-hydrodynamics, imposed magnetic fields

Transport modeling of idealized, cone-guided fast ignition targets indicates the severe challenge posed by fast-electron source divergence. The hybrid particle-in-cell [PIC] code Zuma is run in tandem with the radiation-hydrodynamics code Hydra to model fast-electron propagation, fuel heating, and thermonuclear burn. The fast electron source is based on a 3D explicit-PIC laser-plasma simulation with the PSC code. This shows a quasi two-temperature energy spectrum, and a divergent angle spectrum (average velocity-space polar angle of 52 degrees). Transport simulations with the PIC-based divergence do not ignite for > 1 MJ of fast-electron energy, for a modest 70 micron standoff distance from fast-electron injection to the dense fuel. However, artificially collimating the source gives an ignition energy of 132 kJ. To mitigate the divergence, we consider imposed axial magnetic fields. Uniform fields ~50 MG are sufficient to recover the artificially collimated ignition energy. Experiments at the Omega laser facility have generated fields of this magnitude by imploding a capsule in seed fields of 50-100 kG. Such imploded fields are however more compressed in the transport region than in the laser absorption region. When fast electrons encounter increasing field strength, magnetic mirroring can reflect a substantial fraction of them and reduce coupling to the fuel. A hollow magnetic pipe, which peaks at a finite radius, is presented as one field configuration which circumvents mirroring.Comment: 16 pages, 17 figures, submitted to Phys. Plasma

Propofol and sevoflurane induce distinct burst suppression patterns in rats

Burst suppression is an EEG pattern characterized by alternating periods of high-amplitude activity (bursts) and relatively low amplitude activity (suppressions). Burst suppression can arise from several different pathological conditions, as well as from general anesthesia. Here we review current algorithms that are used to quantify burst suppression, its various etiologies, and possible underlying mechanisms. We then review clinical applications of anesthetic-induced burst suppression. Finally, we report the results of our new study showing clear electrophysiological differences in burst suppression patterns induced by two common general anesthetics, sevoflurane and propofol. Our data suggest that the circuit mechanisms that generate burst suppression activity may differ among general anesthetics

Evaluation of a clinical tool for early etiology identification in status epilepticus.

OBJECTIVES: Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. METHODS: This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. RESULTS: Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4-89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4-96) (κ = 0.81). SIGNIFICANCE: This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment

Variability in pharmacologically-induced coma for treatment of refractory status epilepticus

Objective To characterize the amount of EEG suppression achieved in refractory status epilepticus (RSE) patients treated with pharmacologically-induced coma (PIC). Methods We analyzed EEG recordings from 35 RSE patients between 21–84 years-old who received PIC that target burst suppression and quantified the amount of EEG suppression using the burst suppression probability (BSP). Then we measured the variability of BSPs with respect to a reference level of BSP 0.8 ± 0.15. Finally, we also measured the variability of BSPs with respect to the amount of intravenous anesthetic drugs (IVADs) received by the patients. Results Patients remained in the reference BSP range for only 8% (median, interquartile range IQR [0, 29] %) of the total time under treatment. The median time with BSP below the reference range was 84% (IQR [37, 100] %). BSPs in some patients drifted significantly over time despite constant infusion rates of IVADs. Similar weight-normalized infusion rates of IVADs in different patients nearly always resulted in distinct BSPs (probability 0.93 (IQR [0.82, 1.0]). Conclusion This study quantitatively identified high variability in the amount of EEG suppression achieved in clinical practice when treating RSE patients. While some of this variability may arise from clinicians purposefully deviating from clinical practice guidelines, our results show that the high variability also arises in part from significant inter- and intra- individual pharmacokinetic/pharmacodynamic variation. Our results indicate that the delicate balance between maintaining sufficient EEG suppression in RSE patients and minimizing IVAD exposure in clinical practice is challenging to achieve. This may affect patient outcomes and confound studies seeking to determine an optimal amount of EEG suppression for treatment of RSE. Therefore, our analysis points to the need for developing an alternative paradigm, such as vigilant anesthetic management as happens in operating rooms, or closed-loop anesthesia delivery, for investigating and providing induced-coma therapy to RSE patients

Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios as Prognostic Factors after Stereotactic Radiation Therapy for Early-Stage Non–Small-Cell Lung Cancer

IntroductionThe hematologic indices of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are correlated with clinical outcomes after stereotactic radiation.MethodsWe retrospectively evaluated the pretreatment NLR and PLR in patients treated with stereotactic radiation for early stage non–small-cell lung cancer at our institution. A total of 149 patients treated for non–small-cell lung cancer were identified, and 59 had stage I disease with neutrophil, platelet, and lymphocyte levels within a 3-month period before treatment. Receiver operating characteristic (ROC) analysis was performed to examine cutoff values for survival and nonlocal failure followed by Kaplan–Meier analysis for survival.ResultsWith a median follow-up of 17 months, 28 deaths were observed, and the median overall survival for all patients was 43 months. Based on the ROC analysis, NLR and PLR cutoff values for further survival analysis were determined based on the ROC analysis to be 2.98 and 146. The median overall survival was not reached for patients with low NLR or PLR but the survival was 23 months for patients with high NLR or PLR. There was no correlation between NLR and nonlocal failure, but on multivariate analysis PLR was found to be associated with freedom from nonlocal failure. Nonlocal failure rates were 11% for patients with PLR less than 250 and 58% for PLR greater than 250 (p < 0.001).ConclusionThe pretreatment NLR and PLR represented significant prognostic indicators of survival in patients treated for early-stage non–small-cell lung carcinoma with stereotactic radiation. The PLR may be used as a prognostic indicator for nonlocal failure after stereotactic radiation for early-stage lung cancer

A Large-Scale Synthesis and Characterization of Quaternary CuIn\u3csub\u3e\u3cem\u3ex\u3c/em\u3e\u3c/sub\u3eGa\u3csub\u3e1−\u3cem\u3ex\u3c/em\u3e\u3c/sub\u3eS\u3csub\u3e2\u3c/sub\u3e Chalcopyrite Nanoparticles via Microwave Batch Reactions

Various quaternary CuInxGa1−xS2 (0 ≤ x ≤ 1) chalcopyrite nanoparticles have been prepared from molecular single-source precursors via microwave decomposition. We were able to control the nanoparticle size, phase, stoichiometry, and solubility. Depending on the choice of surface modifiers used, we were able to tune the solubility of the resulting nanoparticles. This method has been used to generate up to 5 g of nanoparticles and up to 150 g from multiple batch reactions with excellent reproducibility. Data from UV-Vis, photoluminescence, X-ray diffraction, TEM, DSC/TGA-MS, and ICP-OES analyses have shown high reproducibility in nanoparticle size, composition, and bandgap

A Large-scale Synthesis and Characterization of Quaternary CuInₓGa₁₋ₓS₂ Chalcopyrite Nanoparticles via Microwave Batch Reactions

Various quaternary CuInxGa1-xS2 (0≤x≤1) chalcopyrite nanoparticles have been prepared from molecular single-source precursors via microwave decomposition. We were able to control the nanoparticle size, phase, stoichiometry, and solubility. Depending on the choice of surface modifiers used, we were able to tune the solubility of the resulting nanoparticles. This method has been used to generate up to 5g of nanoparticles and up to 150g from multiple batch reactions with excellent reproducibility. Data from UV-Vis, photoluminescence, X-ray diffraction, TEM, DSC/TGA-MS, and ICP-OES analyses have shown high reproducibility in nanoparticle size, composition, and bandgap

Translation of immunomodulatory therapy to treat chronic heart failure: Preclinical studies to first in human

BACKGROUND: Inflammation has been associated with progression and complications of chronic heart failure (HF) but no effective therapy has yet been identified to treat this dysregulated immunologic state. The selective cytopheretic device (SCD) provides extracorporeal autologous cell processing to lessen the burden of inflammatory activity of circulating leukocytes of the innate immunologic system. AIM: The objective of this study was to evaluate the effects of the SCD as an extracorporeal immunomodulatory device on the immune dysregulated state of HF. HF. METHODS AND RESULTS: SCD treatment in a canine model of systolic HF or HF with reduced ejection fraction (HFrEF) diminished leukocyte inflammatory activity and enhanced cardiac performance as measured by left ventricular (LV) ejection fraction and stroke volume (SV) up to 4 weeks after treatment initiation. Translation of these observations in first in human, proof of concept clinical study was evaluated in a patient with severe HFrEFHFrEF ineligible for cardiac transplantation or LV LV assist device (LVAD) due to renal insufficiency and right ventricular dysfunction. Six hour SCD treatments over 6 consecutive days resulted in selective removal of inflammatory neutrophils and monocytes and reduction in key plasma cytokines, including tumor necrosis factor-alpha (TNF-α),), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. These immunologic changes were associated with significant improvements in cardiac power output, right ventricular stroke work index, cardiac index and LVSV index…. Stabilization of renal function with progressive volume removal permitted successful LVAD implantation. CONCLUSION: This translational research study demonstrates a promising immunomodulatory approach to improve cardiac performance in HFrEFHFrEF and supports the important role of inflammation in the progression of HFHF