Prevalence, risk factors and outcomes of patients coming from the community with sepsis due to multidrug resistant bacteria

Background: Although previous studies showed an increasing prevalence of infections due to multi-drug resistant (MDR) bacteria in the community, specific data on sepsis are lacking. We aimed to assess prevalence, risk factors and outcomes of patients with sepsis due to MDR bacteria. Methods: An observational, retrospective study was conducted on consecutive adult patients coming from the community and admitted to the Policlinico Hospital, Milan, Italy, with a diagnosis of sepsis between January 2011 and December 2015. Primary study outcome was in-hospital mortality. Results: Among 518 patients, at least one MDR bacteria was isolated in 88 (17%). ESBL+ Enterobacteriaceae were the most prevalent MDR bacteria (9.7%) followed by MRSA (3.9%). Independent risk factors for sepsis due to MDR bacteria were septic shock (OR: 2.2; p = 0.002) and hospitalization in the previous 90 days (OR: 2.3; p = 0.003). Independent risk factors for sepsis due to ESBL+ bacteria were hospitalization in the previous 90 days (OR: 2.1; p = 0.02) and stroke (OR: 2.1; p = 0.04). A significantly higher mortality was detected among patients with vs. without MDR bacteria (40.2% vs. 23.1% respectively, p = 0.001). Independent risk factors for mortality among patients with sepsis were coagulation dysfunction (OR: 3.2; p = 0.03), septic shock (OR: 3.2; p = 0.003), and isolation of a MDR bacteria (OR: 4.6; p < 0.001). Conclusion: In light of the prevalence and impact of MDR bacteria causing sepsis in patients coming from the community, physicians should consider ESBL coverage when starting an empiric antibiotic therapy in patients with specific risk factors, especially in the presence of septic shock

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia

BackgroundPrimary aldosteronism (PA) is characterized by several metabolic changes such as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of non-coding small RNA molecules known to be critical regulators in several cellular processes associated with AT dysfunction. The aim of this study was to evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA) compared to the samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA). MethodsThe quantitative expression of selected miRNA using real-time PCR was analyzed in surrounding adrenal neoplasia, peri-renal, and subcutaneous AT samples of 16 patients with adrenalectomy (11 patients with APA and 5 patients with NFA). ResultsReal-time PCR cycles for miRNA-132, miRNA-143, and miRNA-221 in fat surrounding adrenal neoplasia and in peri-adrenal AT were significantly higher in APA than in patients with NFA. Unlike patients with NFA, miRNA-132, miRNA-143, miRNA-221, and miRNA-26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in patients with APA. ConclusionThis study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in patients with PA

A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome

Background Aggressive mature B-cell non-Hodgkin's lymphomas (BCL) sharing features of Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) (intermediate BL/DLBCL) but deviating with respect to one or more characteristics are increasingly recognized. The limited knowledge about these biologically heterogeneous lymphomas hampers their assignment to a known entity, raising incertitude about optimal treatment approaches. We therefore searched for discriminative, prognostic, and predictive factors for their better characterization. Patients and methods We analyzed 242 cytogenetically defined aggressive mature BCL for differential protein expression. Marker selection was based on recent gene-expression profile studies. Predictive models for diagnosis were established and validated by a different set of lymphomas. Results CSE1L- and inhibitor of DNA binding-3 (ID3)-overexpression was associated with the diagnosis of BL and signal transduction and transcription-3 (STAT3) with DLBCL (P<0.001 for all markers). All three markers were associated with patient outcome in DLBCL. A new algorithm discriminating BL from DLBCL emerged, including the expression of CSE1L, STAT3, and MYC translocation. This ‘new classifier' enabled the identification of patients with intermediate BL/DLBCL who benefited from intensive chemotherapy regimens. Conclusion The proposed algorithm, which is based on markers with reliable staining properties for routine diagnostics, represents a novel valid tool in separating BL from DLBCL. Most interestingly, it allows segregating intermediate BL/DLBCL into groups with different treatment requirement

Digital image analysis and artificial intelligence in pathology diagnostics-the Swiss view

Digital pathology (DP) is increasingly entering routine clinical pathology diagnostics. As digitization of the routine caseload advances, implementation of digital image analysis algorithms and artificial intelligence tools becomes not only attainable, but also desirable in daily sign out. The Swiss Digital Pathology Consortium (SDiPath) has initiated a Delphi process to generate best-practice recommendations for various phases of the process of digitization in pathology for the local Swiss environment, encompassing the following four topics: i) scanners, quality assurance, and validation of scans; ii) integration of scanners and systems into the pathology laboratory information system; iii) the digital workflow; and iv) digital image analysis (DIA)/artificial intelligence (AI). The current article focuses on the DIA-/AI-related recommendations generated and agreed upon by the working group and further verified by the Delphi process among the members of SDiPath. Importantly, they include the view and the currently perceived needs of practicing pathologists from multiple academic and cantonal hospitals as well as private practices

Haemodynamic consequences of changing bicarbonate and calcium concentrations in haemodialysis fluids

Background. In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate haemodialysis induces hypotension. In this study, we have further investigated the changes in systemic haemodynamics induced by bicarbonate and calcium, using non-invasive procedures

Pre-encounter predictions of DART impact ejecta behavior and observability

We overview various efforts within the DART Investigation Team’s Ejecta Working Group to predict the characteristics, quantity, dynamical behavior, and observability of DART impact ejecta. We discuss various methodologies for simulation of the impact/cratering process with their advantages and drawbacks in relation to initializing ejecta for subsequent dynamical propagation through and away from the Didymos system. We discuss the most relevant forces acting on ejecta once decoupled from Dimorphos’s surface and highlight various software packages we have developed and used to dynamically simulate ejecta under the action of those forces. With some additional software packages, we explore the influence of additional perturbing effects, such as interparticle collisions within true N-body codes and nonspherical and rotating particles’ interplay with solar radiation pressure. We find that early-timescale and close-proximity ejecta evolution is highly sensitive to some of these effects (e.g., collisions) while relatively insensitive to other factors. We present a methodology for turning the time-evolving size- and spatially discretized number density field output from ejecta simulations into synthetic images for multiple platforms/cameras over wide-ranging vantage points and timescales. We present such simulated images and apply preliminary analyses to them for nominal and off-nominal cases bracketing realistic total mass of ejecta and ejecta cumulative size–frequency distribution slope. Our analyses foreshadow the information content we may be able to extract from the actual images taken during and after the DART encounter by both LICIACube and Earth-vicinity telescopes.ANII: FCE_1_2019_1_15645

Swiss digital pathology recommendations: results from a Delphi process conducted by the Swiss Digital Pathology Consortium of the Swiss Society of Pathology

Integration of digital pathology (DP) into clinical diagnostic workflows is increasingly receiving attention as new hardware and software become available. To facilitate the adoption of DP, the Swiss Digital Pathology Consortium (SDiPath) organized a Delphi process to produce a series of recommendations for DP integration within Swiss clinical environments. This process saw the creation of 4 working groups, focusing on the various components of a DP system (1) scanners, quality assurance and validation of scans, (2) integration of Whole Slide Image (WSI)-scanners and DP systems into the Pathology Laboratory Information System, (3) digital workflow-compliance with general quality guidelines, and (4) image analysis (IA)/artificial intelligence (AI), with topic experts for each recruited for discussion and statement generation. The work product of the Delphi process is 83 consensus statements presented here, forming the basis for "SDiPath Recommendations for Digital Pathology". They represent an up-to-date resource for national and international hospitals, researchers, device manufacturers, algorithm developers, and all supporting fields, with the intent of providing expectations and best practices to help ensure safe and efficient DP usage

After DART: Using the First Full-scale Test of a Kinetic Impactor to Inform a Future Planetary Defense Mission

NASA’s Double Asteroid Redirection Test (DART) is the first full-scale test of an asteroid deflection technology. Results from the hypervelocity kinetic impact and Earth-based observations, coupled with LICIACube and the later Hera mission, will result in measurement of the momentum transfer efficiency accurate to ∼10% and characterization of the Didymos binary system. But DART is a single experiment; how could these results be used in a future planetary defense necessity involving a different asteroid? We examine what aspects of Dimorphos’s response to kinetic impact will be constrained by DART results; how these constraints will help refine knowledge of the physical properties of asteroidal materials and predictive power of impact simulations; what information about a potential Earth impactor could be acquired before a deflection effort; and how design of a deflection mission should be informed by this understanding. We generalize the momentum enhancement factor β, showing that a particular direction-specific β will be directly determined by the DART results, and that a related direction-specific β is a figure of merit for a kinetic impact mission. The DART β determination constrains the ejecta momentum vector, which, with hydrodynamic simulations, constrains the physical properties of Dimorphos’s near-surface. In a hypothetical planetary defense exigency, extrapolating these constraints to a newly discovered asteroid will require Earth-based observations and benefit from in situ reconnaissance. We show representative predictions for momentum transfer based on different levels of reconnaissance and discuss strategic targeting to optimize the deflection and reduce the risk of a counterproductive deflection in the wrong direction

Expression of MAGE-C1/CT7 and MAGE-C2/CT10 Predicts Lymph Node Metastasis in Melanoma Patients

MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis

Double Asteroid Redirection Test (DART): Structural and Dynamic Interactions between Asteroidal Elements of Binary Asteroid (65803) Didymos

Abstract NASA's Double Asteroid Redirection Test (DART) mission is the first full-scale planetary defense mission. The target is the binary asteroid (65803) Didymos, in which the smaller component Dimorphos (∼164 m equivalent diameter) orbits the larger component Didymos (∼780 m equivalent diameter). The DART spacecraft will impact Dimorphos, changing the system’s mutual orbit by an amount that correlates with DART's kinetic deflection capability. The spacecraft collision with Dimorphos creates an impact crater, which reshapes the body. Also, some particles ejected from the DART impact site on Dimorphos eventually reach Didymos. Because Didymos’s rapid spin period (2.26 hr) may be close to its stability limit for structural failure, the ejecta reaching Didymos may induce surface disturbance on Didymos. While large uncertainties exist, nonnegligible reshaping scenarios on Didymos and Dimorphos are possible if certain conditions are met. Our analysis shows that given a surface slope uncertainty on Dimorphos of 45°, with no other information about its local topography, and if the DART-like impactor is treated as spherical, the ejecta cone crosses Didymos with speeds ≳14 m s−1 in 13% of simulations. Additional work is necessary to determine the amount of mass delivered to Didymos from the DART impact and whether the amount of kinetic energy delivered is sufficient to overcome cohesive forces in those cases. If nonnegligible (but small) reshaping occurs for either of these asteroids, the resulting orbit perturbation and reshaping are measurable by Earth-based observations.</jats:p