Well-established non-destructive testing methods in aero engine industry are time-consuming and expensive with a negative impact on economic viability, especially for parts from additive manufacturing. To improve the economics of electron beam powder bed fusion (PBF-EB), the detection and evaluation of backscattered electrons (BSEs) during the PBF-EB process is a highly promising approach. Electron optical (ELO) images are obtained using the electron beam in a way comparable with scanning electron microscopy. The method is capable of detecting defects (e.g., pores) and the part contour for each layer, thus providing information about the quality of the resulting component. The estimation of dimensional and geometrical accuracy is obtained from the comparison of design data (target geometry) with ELO data (actual geometry). The purpose of our investigation is the utilization of backscattered electron detection as a non-destructive in-situ testing method for additively manufactured aero engine parts of the second component class which includes turbine blades, fuel nozzles and casings.

A major advantage of metal additive manufacturing is the possibility for tool-free production of complex shaped parts. Currently, the geometrical and dimensional accuracy of these parts can only be reliably controlled by time and cost intensive post-process inspection, e.g. using x-ray computed tomography (XCT). The current investigation demonstrates the first in-situ metrology technique for electron beam powder bed fusion (PBF-EB) using electron-optical imaging (ELO). After a calibration experiment, the approach was validated for a PBF-EB build job by comparing in-situ ELO imaging data to XCT data of an as-built part. The quantitative comparison showed a remarkable high agreement between both imaging techniques. It is demonstrated that ELO imaging is capable of making accurate predictions on the geometrical and dimensional accuracy of the as-build part. This result is the basis of new possibilities for in-situ process and quality control in PBF-EB.

Background:Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.Methods:In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.Results:Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall.Conclusions:In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

The current study evaluates the capabilities of electron-optical (ELO) in situ imaging with respect to monitoring and prediction of manufacturing precision in electron beam powder bed fusion. Post-process X-ray computed tomography of two different as-built parts is used to quantitatively evaluate the accuracy and limitations of ELO imaging. Additionally, a thermodynamic simulation is performed to improve the understanding of ELO data and to assess the feasibility of predicting dimensional accuracy numerically. It is demonstrated that ELO imaging captures the molten layers accurately (deviations <100 μm) and indicates the creation of surface roughness. However, some geometrical features of the as-built parts exhibit local inaccuracies associated with thermal stress-induced deformation (deviations up to 500 μm) which cannot be captured by ELO imaging. It is shown that the comparison between in situ and post-process data enables a quantification of these effects which might provide the possibility for developing effective countermeasures in the future.

OBJECTIVES:The Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal exam to exclude endogenous Candida endophthalmitis. Our objective was to determine if there are significant risk factors in candidemic patients for developing endogenous Candida endophthalmitis METHODS: We conducted a retrospective study of all candidemic patients at three academic medical centers between 2012 and 2017. We extracted risk factors for Candida endophthalmitis based on prior literature and compared them between patients with and without endophthalmitis. We then built a multivariate logistic regression model to assess which ones were significant. RESULTS:We found 771 patients with candidemia. 120 (15.6%) of these patients were diagnosed with Candida endophthalmitis. In our logistic regression analysis, central venous catheter presence (OR 8.35), intravenous drug use (OR 4.76), immunosuppression (OR 2.40), total parenteral nutrition recipient (OR 2.28), race (OR 1.65), age (OR 1.02), and gender (OR 0.57) were risk factors for developing Candida endophthalmitis. Additionally, Candida albicans was more likely to result in Candida endophthalmitis (OR 1.86). CONCLUSIONS:This cohort represents the largest study of risk factors for candidemic patients who developed endogenous Candida endophthalmitis. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening.

Thermal expansion plays an important role during additive manufacturing by electron beam powder bed fusion because it strongly affects the quality of the manufactured parts. However, prediction and control of thermal expansion is a difficult task due to the high complexity of part geometries and the corresponding temperature distribution. Therefore, powerful process monitoring tools are required to improve insight into the process. In the current study, the capabilities of in-situ acquisition of electron optical images are assessed with respect to measurement of thermal expansion. For this purpose, a large series of electron-optical images was recorded during cooling down of a PBF-EB build job. The subsequent image analysis revealed that the image quality is high enough to monitor thermal shrinkage of the part and to quantify thermal strain with remarkable accuracy. These findings are very promising and give rise to new applications of in-situ electron-optical observation with regard to temperature management and validation of numerical frameworks.

Process parameters for manufacturing of complex parts in electron beam powder bed fusion are usually derived from material-specific process windows, which are established by fabrication and evaluation of standardized cuboid specimen. The mechanisms defining low- and high-energy boundaries of the process window are well understood. The boundary emerging at high scan speeds and beam power however, was observed but the underlying mechanism is not further discussed. In addition, appropriate methodologies to transfer process parameters from standardized process windows to complex geometries are not readily available, as the meltpool geometry is significantly affected by the scan length. This work introduces and verifies a characteristic scan length dependent process parameter limit for the fabrication of complex geometries. Electron-optical process monitoring enables the surface characterization for a wide range of process parameter and the subsequent identification of the process parameter limit as a linear function of scan length. A semi-analytical heat conduction model is used to examine the corresponding meltpool geometries. The underlying mechanism is determined as the meltpool stability limit, which occurs, when the aspect ratio of the meltpool reaches the threshold for a liquid film instability. Based on the meltpool geometries for different scan lengths, an analytical relationship for the process parameter limit as a function of scan length is proposed. This relationship may be used as a guideline for the selection of process parameters and the development of new scan strategies for the fabrication of complex geometries.

Background A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value. Case presentation We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis. Conclusions This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.

Materials processed by additive manufacturing often exhibit a very fine-scaled microstructures due to high cooling rates in the process. In this study, single-layer surface electron beam melting is used to create very high cooling rates similar to additive manufacturing processes to investigate the resulting microstructure. In the case of Nb-Si-Cr in-situ composites, a nano-scaled eutectic microstructure is beneficial for improving the mechanical and oxidational properties. Fast solidification results in the formation of supersaturated phases of Nb ss and Cr 2 Nb with phase diameters down to 10 nm as well as in the stabilization of the metastable Nb 9 (Cr,Si) 5 phase at room temperature. After processing with different solidification rates, the decomposition of the Nb 9 (Cr,Si) 5 phase has been studied in detail with atom probe microscopy. The stabilization of mixed silicide phases by electron beam melting shows a new pathway for improving hardness and enhancing oxidation resistance of nanostructured eutectic in-situ composites, by which the inherent weaknesses of Nb-Si-Cr can be overcome without further alloying elements. Graphical Abstract

Eutectic NiAl-(Cr,Mo) composites are promising high temperature materials due to their high melting point, excellent oxidation behavior and low density. To enhance the strength, hardness and fracture toughness, high cooling rates are beneficial to obtain a fine cellular-lamellar microstructure. This can be provided by the additive process of selective electron beam melting. The very high temperature gradient achieved in this process leads to the formation of the finest microstructure that has ever been reported for NiAl-(Cr,Mo) in-situ composites. A very high hardness and fracture toughening mechanisms were observed. This represents a feasibility study towards additive manufacturing of eutectic NiAl-(Cr,Mo) in-situ composites by selective electron beam melting.

Additive manufacturing by electron beam melting (EBM) is a complex process, which still lacks reliable tools for process monitoring. Demanding processing conditions such as high temperature, high vacuum, and X‐ray radiation impede the continuous operation of standard process monitoring devices such as light‐optical camera systems. To overcome this deficit, the detection of backscattered electrons (BSEs) is a highly promising approach. A detection system for BSEs is used for recording the in operando signal during melting inside an EBM system. The acquired data are postprocessed by mapping the data points to spatial coordinates. A comparison between the obtained intensity map and the as‐built surface shows a remarkable correlation, which might be suitable for process monitoring and quality control purposes.

The availability of a reliable processing window is the basic requirement for processing new materials via selective electron beam melting (SEBM). Typically, these processing windows are derived by a time-consuming procedure comprising fabrication, metallographic preparation and analysis of standardized specimens for every parameter set. This study demonstrates the immediate development of a processing window during one single SEBM process. An electron optical image acquisition system provides the necessary information for evaluation and subsequent adaption of process parameters. It is shown that this immediate approach delivers processing windows with sufficient accuracy, while the required time is substantially reduced from weeks or even months to several hours. (C) 2019 Elsevier B.V. All rights reserved.

Abstract Background In this prospective nation-wide survey of bloodstream isolates associated with first episode of FN in high-risk cancer patients from 14 US cancer centers (December 2016 and June 2018), viridans group Streptococci (VGS) were the most common Gram-positive isolate. We sought to clinically and microbiologically characterize VGS bloodstream infections (BSI). Methods Among 343 patients,we compared 90 with VGS vs 253 with non-VGS BSI. Minimum inhibitory concentrations for blood culture isolates were determined by broth dilution for selected agents at our reference microbiology laboratory (UNMC). Clinical data were electronically captured in RedCap, including local site isolate identification and confirmatory reference lab identification via MALDI. Categorical and continuous variables were assessed via chi-square and Mann–Whitney U tests, respectively. Results Ninety-two VGS isolates were identified among 90 FN patients, representing 27% of all BSI isolates. S. mitis or oralis comprised 64 (70%) of VGS. There were no differences between age, sex, and primary diagnosis (50% with AML) among the 2 groups; 1/3 were HSCT recipients. Fluoroquinolone prophylaxis was used in 64 (71%) vs. 139 (55%), P < 0.01, in VGS vs non-VGS groups. Critical illness composite (new need for pressor(s), mechanical ventilation or death within 30 days) was 6 (7%) vs. 44 (17%), P = 0.01, in the VGS vs non-VGS groups. Figure 1 displays an overview of antibiotic susceptibilities for 79 testable isolates. VGS susceptibilities to levofloxacin, penicillin, and ceftriaxone were 39%, 47%, and 94%, respectively. Conclusion VGS are common pathogens in FN patients. Prior fluoroquinolone prophylaxis use may be a risk factor. VGS BSI was not associated with increased critical illness compared with non-VGS. Finally, assuming ceftriaxone susceptibility confers that of cefepime, >90% of VGS are susceptible to empiric FN cefepime regimens. Disclosures All authors: No reported disclosures.

Abstract Background The Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal examination to exclude invasive ocular candidiasis. However, it remains unclear whether there are patients with candidemia who do not warrant routine surveillance because the risk of ocular infection is low. Methods We conducted a retrospective cohort study of all patients with candidemia diagnosed at three academic medical centers (Duke, University of North Carolina and University of Virginia) from 2012 to 2017. We collected risk factors for invasive ocular candidiasis based on previous literature and compared them between patients with and without invasive ocular candidiasis. We then built a multivariate logistic regression model to assess which risk factors were significant for developing invasive ocular candidiasis. Results Overall, 942 patients were diagnosed with candidemia over the study period. The mean age was 55.9 years, 56% were men, 25% were non-White. Among these patients, 120 (13%) were also diagnosed with invasive ocular candidiasis, 10% with chorioretinitis and 3% with vitreous involvement. In our logistic regression analysis, central venous catheter presence [OR 8.35 (3.53, 19.77)], intravenous drug use [OR 5.02 (2.63, 9.58)], immunosuppression [OR 2.40 (1.55, 3.70)], total parenteral nutrition [OR 2.28 (1.42, 3.66)], non-White race [OR 1.65 (1.07, 2.55)], older age [OR 1.02 (1.01, 1.03)],and female gender [OR 0.57 (0.37, 0.89)] were risk factors for developing invasive ocular candidiasis. In addition, we found that persons with candidemia due to C. albicans were more likely to have invasive ocular candidiasis [OR 1.86 (1.22, 2.85)]. Conclusion This cohort represents the largest study of patients with candidemia who developed invasive ocular candidiasis to date. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening. Disclosures All authors: No reported disclosures.

Purpose The purpose of this study is the introduction and validation of a new technique for process monitoring during electron beam melting (EBM). Design/methodology/approach In this study, a backscatter electron detector inside the building chamber is used for image acquisition during EBM process. By systematic variation of process parameters, the ability of displaying different topographies, especially pores, is investigated. The results are evaluated in terms of porosity and compared with optical microscopy and X-ray computed tomography. Findings The method is capable of detecting major flaws (e.g. pores) and gives information about the quality of the resulting component. Originality/value Image acquisition by evaluating backscatter electrons during EBM process is a new approach in process monitoring which avoids disadvantages restricting previously investigated techniques.

Abstract Background Blood stream infection (BSI) during neutropenia is associated with high risk for morbidity and mortality in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplant (HCT). We sought to identify factors associated with increased risk for critical illness (CI) morbidities within 7 days of BSI with index FN following chemotherapy. Methods A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with blood stream infection (BSI) during first FN after cytotoxic chemotherapy or HCT. We evaluated factors influencing poor outcomes defined as critical illness (need for pressor support, mechanical ventilation, new pneumonia or new BSI) within 7 days of BSI with index FN. Concordance between antibiotic and BSI isolate was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with the initial antimicrobial regimen (IAR) used, for single organism bacteremias only. Results Among 294 FN bacteremic episodes (93 HCT) were 336 bacterial pathogens (48.5% Gram-negative [GN], 46.5% Gram-positive [GP], and 6% anaerobes). Death occurred in 11/294 (4%) and 41/294 (14%) had CI by day 8. At FN presentation, mean MASCC score of those with CI vs. those without was 16.9 vs. 18.6 (P = 0.03) and there was a trend toward higher mean PITT scores for patients with CI by day 8 vs. those without (1.54 vs. 0.82 (P = 0.08)). Among GN bacteremias, 15% developed CI vs. 14.5% in nonviridans group Streptococci (VGS) GP bacteremias, and 10.9% in VGS bacteremias (NS). Among patients with single organism bacteremias (88% of all BSI), mismatch of IAR coverage with isolate susceptibilities occurred in 16.7% (38/227). Among patients whom IAR was active vs. inactive against BSI isolate, 16% vs 14.3%, respectively, developed CI (P = 0.81). Conclusion These data indicate that the MASCC score applied to high-risk inpatients may be a predictor for CI in the first week after bacteremia FN. The PITT shows less correlation with poor outcomes. There was no association between isolate type (GN, GP, or VGS) and CI. Notably there was no association between mismatched BSI susceptibility and antimicrobial spectrum of the IAR and early CI. Disclosures A. G. Freifeld, Merck: Investigator, Research grant. A. Zimmer, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee. Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant. JMI Laboratories: Investigator, Research grant. Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient. Astellas: Investigator, Grant recipient. Shionogi (Japan): Investigator, Grant recipient. Gilead: Investigator, Grant recipient. Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant. Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Scynexis: Grant Investigator, Research grant. Amplyx: Grant Investigator, Research grant. Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit. Y. Zhang, Merck: Investigator, Research grant. J. Meza, Merck: Investigator, Research grant.

The empiric initial antibiotic regimen (IAR) for treatment of febrile neutropenia (FN) relies on a knowledge of epidemiology and susceptibility patterns of bacterial bloodstream infections (BSI), especially in high-risk patient populations, i.e., those receiving chemotherapy for hematologic malignancies (HM) or undergoing hematopoietic stem cell transplant (HCT). As the last US national survey of BSI epidemiology in cancer patients was published in 2003, we sought to update these data focusing exclusively on high-risk patients with attention to IARs used and their concordance with susceptibilities of isolated bloodstream pathogens. A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with BSI during first FN after cytotoxic chemotherapy or HCT. Concordance between antibiotic and BSI was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with IAR used, for single organism bacteremias only. Among 294 FN bacteremic episodes (93 HCT), there were 336 bacterial pathogens (48.5% Gram negative [GN] 46.5% Gram positive [GP] and 6% anaerobes), with 88% monomicrobial episodes. E. coli and viridans group Streptococci (VGS) were the most commonly isolated GN and GP, respectively, each accounting for nearly 25% of total organisms identified. IARs included cefepime 61%, piperacillin–tazobactam 24%, and meropenem 8%. Isolates were nonsusceptible to the IAR in 38/227 (17%) of FN episodes. Antibiotic mismatch was more likely to occur with a non-VGS GP (37%) vs. GN (13%) or VGS (2%) P < 0.001. This is the first US national survey of high-risk BSI in FN. Although mismatch between BSI and IAR occurs in 17% of FN bacteremia episodes, this is driven primarily by non-VGS GP isolates such as CoNS and MRSA. Currently used IARs, comprised primarily of cefepime and piperacillin–tazobactam, generally provide reliable coverage for GN isolates across the United States (87%) but careful tracking of this rate is essential to identify further erosion of coverage in the current era of antimicrobial resistance. A. Zimmer, Merck: Investigator, Research grant. A. G. Freifeld, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee; Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient; Astellas: Investigator, Grant recipient; Shionogi (Japan): Investigator, Grant recipient; Gilead: Investigator, Grant recipient; Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit.. J. Meza, Merck: Investigator, Research grant. Y. Zhang, Merck: Investigator, Research grant.

Objective The objective of this study was to determine the time to hematologic recovery and the incidence of secondary sepsis and mortality among neutropenic infants treated or not treated with granulocyte colony-stimulating factor (G-CSF).Study Design We identified all neutropenic infants discharged from 348 neonatal intensive care units from 1997 to 2012. Neutropenia was defined as an absolute neutrophil count <= 1,500/mu L for >= 1 day during the first 120 days of life. Incidence of secondary sepsis and mortality and number of days required to reach an absolute neutrophil count > 1,500/mu L for infants exposed to G-CSF were compared with those of unexposed infants.Results We identified 30,705 neutropenic infants, including 2,142 infants (7%) treated with G-CSF. Treated infants had a shorter adjusted time to hematologic recovery (hazard ratio: 1.36, 95% confidence interval [CI]: 1.30-1.44) and higher adjusted odds of secondary sepsis (odds ratio [OR]: 1.50, 95% CI: 1.20-1.87), death (OR: 1.33, 95% CI: 1.05-1.68), and the combined outcome of sepsis or death (OR: 1.41, 95% CI: 1.19-1.67) at day 14 compared with untreated infants. These differences persisted at day 28.Conclusion G-CSF treatment decreased the time to hematologic recovery but was associated with increased odds of secondary sepsis and mortality in neutropenic infants. G-CSF should not routinely be used for infants with neutropenia.

The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.