Predicting 30-Day Mortality in Hospitalized Patients with Community-Acquired Pneumonia Using Statistical and Machine Learning Approaches

Background: Predicting if a hospitalized patient with community-acquired pneumonia (CAP) will or will not survive after admission to the hospital is important for research purposes as well as for institution of early patient management interventions. Although population-level mortality prediction scores for these patients have been around for many years, novel patient-level algorithms are needed. The objective of this study was to assess several statistical and machine learning models for their ability to predict 30-day mortality in hospitalized patients with CAP. Methods: This was a secondary analysis of the University of Louisville (UofL) Pneumonia Study database. Six different statistical and/or machine learning methods were used to develop patientlevel prediction models for hospitalized patients with CAP. For each model, nine different statistics were calculated to provide measures of the overall performance of the models. Results: A total of 3249 unique hospitalized patients with CAP were enrolled in the study, 2743 were included in the model building (training) dataset, while the remaining 686 were included in the testing dataset. From the full population, death at 30-days post discharge was documented in 458 (13.4%) patients. All models resulted in high variation in the ability to predict survivors and non-survivors at 30 days. Conclusions: In conclusion, this study suggests that accurate patient-level prediction of 30-day mortality in hospitalized patients with CAP is difficult with statistical and machine learning approaches. It will be important to evaluate novel variables and other modeling approaches to better predict poor clinical outcomes in these patients to ensure early and appropriate interventions are instituted

Lung Cytokines and Systemic Inflammation in Patients with COPD

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by lung and systemic inflammation. The role of cytokines in local and systemic inflammation in COPD is not well understood. This study aimed to compare plasma and bronchoalveolar lavage (BAL) fluid cytokine levels in COPD and non-COPD subjects with the intent of better understand their potential roles in driving local and systemic inflammation. Methods: This cross-sectional study analyzed data from 65 subjects: 31 with COPD confirmed by spirometry and 34 non-COPD controls. All subjects underwent spirometry, plasma sample collection, and bronchoscopy/BAL. Levels of 21 inflammatory cytokines were measured in the plasma (systemic inflammation) and BAL (lung inflammation) using a multiplex assay. Results:COPD subjects were overall older (median age 59 vs 36; p = Conclusion: Elevated levels of cytokines were identified in the plasma of COPD subjects when compared to controls, supporting the role of these mediators as one of the mechanisms of systemic inflammation in COPD. In contrast, lung cytokines were not elevated suggesting that inflammation in the setting of COPD may not originate and/or perpetuate in the lungs, or that the BAL fluid is not an optimal source of information when evaluating inflammation in COPD. Although the role of these cytokines remains uncertain, anti-cytokine therapy might modulate inflammation in COPD and perhaps improve outcomes

Using Cluster Analysis of Cytokines to Identify Patterns of Inflammation in Hospitalized Patients with Community-acquired Pneumonia:A Pilot Study

Purpose: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies

Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness. DOI: http://dx.doi.org/10.7554/eLife.04499.00

Neutrophil Function in Elderly Patients Hospitalized with Community- Acquired Pneumonia

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP. Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H2O2) production. The Mann-Whitney U-test was used to compare differences in neutrophil function. Results: A total of 12 HC, 28 NE-CAP, and 12 E-CAP were evaluated. There were no significant differences between NE-CAP and E-CAP patients in regard to CD35 expression (p=0.465), CD66b expression (p=0.601), phagocytosis (p=0.654), or H2O2 production (p=0.541) Conclusions: We failed to demonstrate any significant difference in neutrophil function in nonelderly versus elderly patients hospitalized with CAP in relation to membrane expression of CD35 and CD66b, phagocytosis, and respiratory burst. Abnormal neutrophil function is unlikely to be an important component of the immunosenescence described in elderly patients with CAP

Music, computing and health: A roadmap for the current and future roles of music technology for health care and well-being.

Health and self-regulatio

Quantification of unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples

Hypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation. QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types. Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits. In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings

Fungal biodiversity profiles 21–30

The authors describe ten new taxa for science using mostly both morphological and molecular data. In Basidiomycota, descriptions are provided for Botryobasidium fusisporum sp. nov., B. triangulosporum sp. nov., Cantharellus hydnoides sp. nov. and Hydnum aerostatisporum sp. nov. in Cantharellales; Lactarius rahjamalensis sp. nov. and Russula pseudoaurantiophylla sp. nov. in Russulales and for Mycena paraguayensis comb. nov. in Agaricales. In Ascomycota and hyphomycetes, descriptions are provided for Colletotrichurn eryngiicola sp. nov. (Glomerellales), Corynesporella indica sp. nov. (incertae sedis) and Repetophragma zygopetali sp. nov. (Microthyriales)