Using quantitative breath sound measurements to predict lung function following resection

<p>Abstract</p> <p>Background</p> <p>Predicting postoperative lung function is important for estimating the risk of complications and long-term disability after pulmonary resection. We investigated the capability of vibration response imaging (VRI) as an alternative to lung scintigraphy for prediction of postoperative lung function in patients with intrathoracic malignancies.</p> <p>Methods</p> <p>Eighty-five patients with intrathoracic malignancies, considered candidates for lung resection, were prospectively studied. The projected postoperative (ppo) lung function was calculated using: perfusion scintigraphy, ventilation scintigraphy, and VRI. Two sets of assessments made: one for lobectomy and one for pneumonectomy. Clinical concordance was defined as both methods agreeing that either a patient was or was not a surgical candidate based on a ppoFEV₁% and ppoDLCO% > 40%.</p> <p>Results</p> <p>Limits of agreement between scintigraphy and VRI for ppo following lobectomy were -16.47% to 15.08% (mean difference = -0.70%;95%CI = -2.51% to 1.12%) and for pneumonectomy were -23.79% to 19.04% (mean difference = -2.38%;95%CI = -4.69% to -0.07%). Clinical concordance between VRI and scintigraphy was 73% for pneumonectomy and 98% for lobectomy. For patients who had surgery and postoperative lung function testing (<it>n </it>= 31), ppoFEV₁% using scintigraphic methods correlated with measured postoperative values better than projections using VRI, (adjusted R²= 0.32 scintigraphy; 0.20 VRI), however the difference between methods failed to reach statistical significance. Limits of agreement between measured FEV₁% postoperatively and ppoFEV₁% based on perfusion scintigraphy were -16.86% to 23.73% (mean difference = 3.44%;95%CI = -0.29% to 7.16%); based on VRI were -19.56% to 28.99% (mean difference = 4.72%;95%CI = 0.27% to 9.17%).</p> <p>Conclusions</p> <p>Further investigation of VRI as an alternative to lung scintigraphy for prediction of postoperative lung function is warranted.</p

Using data-driven rules to predict mortality in severe community acquired pneumonia

Prediction of patient-centered outcomes in hospitals is useful for performance benchmarking, resource allocation, and guidance regarding active treatment and withdrawal of care. Yet, their use by clinicians is limited by the complexity of available tools and amount of data required. We propose to use Disjunctive Normal Forms as a novel approach to predict hospital and 90-day mortality from instance-based patient data, comprising demographic, genetic, and physiologic information in a large cohort of patients admitted with severe community acquired pneumonia. We develop two algorithms to efficiently learn Disjunctive Normal Forms, which yield easy-to-interpret rules that explicitly map data to the outcome of interest. Disjunctive Normal Forms achieve higher prediction performance quality compared to a set of state-of-the-art machine learning models, and unveils insights unavailable with standard methods. Disjunctive Normal Forms constitute an intuitive set of prediction rules that could be easily implemented to predict outcomes and guide criteria-based clinical decision making and clinical trial execution, and thus of greater practical usefulness than currently available prediction tools. The Java implementation of the tool JavaDNF will be publicly available. © 2014 Wu et al

Vascular Endothelial Growth Factor Receptor-3 Directly Interacts with Phosphatidylinositol 3-Kinase to Regulate Lymphangiogenesis

Background Dysfunctional lymphatic vessel formation has been implicated in a number of pathological conditions including cancer metastasis, lymphedema, and impaired wound healing. The vascular endothelial growth factor (VEGF) family is a major regulator of lymphatic endothelial cell (LEC) function and lymphangiogenesis. Indeed, dissemination of malignant cells into the regional lymph nodes, a common occurrence in many cancers, is stimulated by VEGF family members. This effect is generally considered to be mediated via VEGFR-2 and VEGFR-3. However, the role of specific receptors and their downstream signaling pathways is not well understood. Methods and Results Here we delineate the VEGF-C/VEGF receptor (VEGFR)-3 signaling pathway in LECs and show that VEGF-C induces activation of PI3K/Akt and MEK/Erk. Furthermore, activation of PI3K/Akt by VEGF-C/VEGFR-3 resulted in phosphorylation of P70S6K, eNOS, PLCc1, and Erk1/2. Importantly, a direct interaction between PI3K and VEGFR-3 in LECs was demonstrated both in vitro and in clinical cancer specimens. This interaction was strongly associated with the presence of lymph node metastases in primary small cell carcinoma of the lung in clinical specimens. Blocking PI3K activity abolished VEGF-C-stimulated LEC tube formation and migration. Conclusions Our findings demonstrate that specific VEGFR-3 signaling pathways are activated in LECs by VEGF-C. The importance of PI3K in VEGF-C/VEGFR-3-mediated lymphangiogenesis provides a potential therapeutic target for the inhibition of lymphatic metastasis

Characterising chromosome rearrangements: recent technical advances in molecular cytogenetics

Genomic rearrangements can result in losses, amplifications, translocations and inversions of DNA fragments thereby modifying genome architecture, and potentially having clinical consequences. Many genomic disorders caused by structural variation have initially been uncovered by early cytogenetic methods. The last decade has seen significant progression in molecular cytogenetic techniques, allowing rapid and precise detection of structural rearrangements on a whole-genome scale. The high resolution attainable with these recently developed techniques has also uncovered the role of structural variants in normal genetic variation alongside single-nucleotide polymorphisms (SNPs). We describe how array-based comparative genomic hybridisation, SNP arrays, array painting and next-generation sequencing analytical methods (read depth, read pair and split read) allow the extensive characterisation of chromosome rearrangements in human genomes