Bacterial infection profiles in lung cancer patients with febrile neutropenia

<p>Abstract</p> <p>Background</p> <p>The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France.</p> <p>Methods</p> <p>We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm³) and fever (temperature > 38.3°C).</p> <p>Results</p> <p>The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. <it>Staphylococcus </it>species (mainly <it>S. aureus</it>) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm³.</p> <p>Conclusion</p> <p>Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.</p

Elevated Peripheral Neutrophils and Matrix Metalloproteinase 9 as Biomarkers of Functional Outcome Following Subarachnoid Hemorrhage

There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (N = 55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6–8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0–14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (N = 35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (p = 0.0003) and neutrophil (p = 0.0002) counts during post-SAH days 0–14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2–3, p = 0.018), blood MMP-9 (post-SAH days 4–5, p = 0.045), and CSF MMP-9 (post-SAH days 2–3, p = 0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6–8, R = 0.39; p = 0.055; post-SAH days 10–14, R = 0.79; p < 0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4–5, R = 0.72; p = 0.0002). Elevation of CSF MMP-9 during post-SAH days 0–14 is associated with poor 3-month outcome (p = 0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy

Regional differentiation of felid vertebral column evolution: a study of 3D shape trajectories

Recent advances in geometric morphometrics provide improved techniques for extraction of biological information from shape and have greatly contributed to the study of ecomorphology and morphological evolution. However, the vertebral column remains an under-studied structure due in part to a concentration on skull and limb research, but most importantly because of the difficulties in analysing the shape of a structure composed of multiple articulating discrete units (i.e. vertebrae). Here, we have applied a variety of geometric morphometric analyses to three-dimensional landmarks collected on 19 presacral vertebrae to investigate the influence of potential ecological and functional drivers, such as size, locomotion and prey size specialisation, on regional morphology of the vertebral column in the mammalian family Felidae. In particular, we have here provided a novel application of a method—phenotypic trajectory analysis (PTA)—that allows for shape analysis of a contiguous sequence of vertebrae as functionally linked osteological structures. Our results showed that ecological factors influence the shape of the vertebral column heterogeneously and that distinct vertebral sections may be under different selection pressures. While anterior presacral vertebrae may either have evolved under stronger phylogenetic constraints or are ecologically conservative, posterior presacral vertebrae, specifically in the post-T10 region, show significant differentiation among ecomorphs. Additionally, our PTA results demonstrated that functional vertebral regions differ among felid ecomorphs mainly in the relative covariation of vertebral shape variables (i.e. direction of trajectories, rather than in trajectory size) and, therefore, that ecological divergence among felid species is reflected by morphological changes in vertebral column shape

Vasculogenesis and Angiogenesis in VEGF Receptor-1 Deficient Mice

Vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1 is a transmembrane tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF). VEGFR-1 is an enigmatic molecule whose precise role in postnatal angiogenesis remains controversial. Although many postnatal and adult studies have been performed by manipulating VEGFR-1 ligands, including competitive binding by truncated VEGFR-1 protein, neutralization by antibodies, or specific ligand overexpression or knockout, much less is known at the level of the receptor per se, especially in vivo. Perplexingly, while VEGFR-1 negatively regulates endothelial cell differentiation during development, it has been implied in promoting angiogenesis under certain conditions in adult tissues, especially in tumors and ischemic tissues. Additionally, it is unclear how VEGFR-1 is involved in vascular maturation and maintenance of vascular quiescence in adult tissues. To facilitate further investigation, we generated a conditional knockout mouse line for VEGFR-1 and characterized angiogenesis in postnatal and adult mice, including angiogenesis in ischemic myocardium. We discuss these findings in the context of the interplay between VEGF family members and their receptors, and summarize various mouse models in the VEGF pathway