A trial of intracranial pressure monitoring in traumatic brain injury

Background Intracranial pressure (ICP) monitoring is considered the standard of care for severe traumatic brain injury (TBI) and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. Methods Objective: The objective was to compare efficacy of guideline-based management in which a protocol for monitoring intraparenchymal ICP was used (ICP group) or a protocol in which treatment was based on imaging and clinical examination (exam group). Design: A multicenter randomized controlled trial was conducted. Setting: The trial was set in ICUs in Bolivia or Ecuador. Subjects: Patients had severe TBI (n = 324) and were 13 years of age or older. Interventions: Patients were randomly allocated to ICP This composite measure was based on performance across 21 measures of functional and cognitive status and was calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). Results There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score 56 in the pressure-monitoring group versus 53 in the imaging-clinical examination group; P= 0.49). Six-month mortality rates were 39% in the pressuremonitoring group and 41% in the imaging-clinical examination group (P = 0.60). The median lengths of stay in the ICU were similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imagingclinical examination group; P = 0.25), although the number of days of brain-specific treatments (for example, administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 versus 3.4, P = 0.002). The distributions of serious adverse events were similar in the two groups. Conclusions For patients with severe TBI, care focused on maintaining monitored ICP at 20 mmHg or less was not shown to be superior to care based on imaging and clinical examination. monitoring or clinical exam-based monitoring. Outcomes: The primary outcome was a composite of survival time, impaired consciousness, functional status at 3 and 6 months, and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of the protocol assignment. © 2014 BioMed Central Ltd

Comparison of chemotherapy and hematopoietic stem cell transplantation pre and postterm DMFT scores: A preliminary study

Aims: Chemotherapy is frequently used as a conditioning regimen to destroy malignant marrow cells before transplantation. Xerostomia, dysphagia, altered taste perception, mucositis, soft‑tissue ulceration, and infection are common adverse oral effects of chemotherapy. The study was aimed to compare decayed, missing, filled teeth (DMFT) scores before and after hematopoietic stem cell transplantation (HSCT) and chemotherapy.Materials and Methods: Thirty‑six patients undergoing HSCT were included in the study. Apre‑HSCT dental treatment protocol was implemented that consisted of restoration of all active carious lesions, treatment of periodontal infections, and extraction of all teeth with advanced periodontal disease. Upon completion of dental treatment, the importance of rigorous and effective oral hygiene was reemphasized, and patients were recalled 6 months later. DMFT scores were calculated prior to the initiation of HSCT treatment and 6 months after transplantation.Statistical Analysis Used: Regression analysis was used to evaluate the effects of HSCT and chemotherapy on DMFT scores.Results: Wilcoxon T test showed a statistically significant difference in DMFT scores before and after HSCT (P < 0.001). Conclusions: DMFT scores were found to increase after chemotherapy and HSCT, suggesting that the risk of infection is higher among HSCT patients when compared to other individuals. The results emphasize the need for dental examinations as an integral part of examination and treatment planning for patients undergoing HSCT and chemotherapy.Key words: Chemotherapy, decayed missing filled teeth scores, hematopoietic stem cell transplantatio

Impact of pro-domain stability of matrix metalloproteinase-8 on the outcome of sepsis

Citation: Berx, B., M. Dickey-Collas, M.D. Skogen, Y.-H. De Roeck, H. Klein, R. Barciela, R.M. Forster, E. Dombrowsky, M. Huret, M. Payne, Y. Sagarminaga, and C. Schrum. 2011. Does operational oceanography address the needs of fisheries and applied environmental scientists? Oceanography 24(1):166–171, doi:10.5670/oceanog.2011.14.Although many oceanographic data products are now considered operational, continued dialogue between data producers and their user communities is still needed. The fisheries and environmental science communities have often been criticized for their lack of multidisciplinarity, and it is not clear whether recent developments in operational oceanographic products are addressing these needs. The International Council for the Exploration of the Sea (ICES) Working Group on Operational Oceanographic products for Fisheries and Environment (WGOOFE) identified a potential mismatch between user requirements and the perception of requirements by the providers. Through a questionnaire (98 respondents), WGOOFE identified some of these issues. Although products of physical variables were in higher demand, several biological parameters scored in the top 10 rankings. Users placed specific focus on historic time series products with monthly or annual resolution and updating on similar time scales. A significant percentage requested access to numerical data rather than graphical output. While the outcomes of this survey challenge our views of operational oceanography, several initiatives are already attempting to close the gap between user requirements and products available

Farsighted Risk Mitigation of Lateral Movement Using Dynamic Cognitive Honeypots

Lateral movement of advanced persistent threats has posed a severe security challenge. Due to the stealthy and persistent nature of the lateral movement, defenders need to consider time and spatial locations holistically to discover latent attack paths across a large time-scale and achieve long-term security for the target assets. In this work, we propose a time-expanded random network to model the stochastic service links in the user-host enterprise network and the adversarial lateral movement. We design cognitive honeypots at idle production nodes and disguise honey links as service links to detect and deter the adversarial lateral movement. The location of the honeypot changes randomly at different times and increases the honeypots' stealthiness. Since the defender does not know whether, when, and where the initial intrusion and the lateral movement occur, the honeypot policy aims to reduce the target assets' Long-Term Vulnerability (LTV) for proactive and persistent protection. We further characterize three tradeoffs, i.e., the probability of interference, the stealthiness level, and the roaming cost. To counter the curse of multiple attack paths, we propose an iterative algorithm and approximate the LTV with the union bound for computationally efficient deployment of cognitive honeypots. The results of the vulnerability analysis illustrate the bounds, trends, and a residue of LTV when the adversarial lateral movement has infinite duration. Besides honeypot policies, we obtain a critical threshold of compromisability to guide the design and modification of the current system parameters for a higher level of long-term security. We show that the target node can achieve zero vulnerability under infinite stages of lateral movement if the probability of movement deterrence is not less than the threshold

The Role of the Receptor for Advanced Glycation End-Products in a Murine Model of Silicosis

Background: The role of the receptor for advanced glycation end-products (RAGE) has been shown to differ in two different mouse models of asbestos and bleomycin induced pulmonary fibrosis. RAGE knockout (KO) mice get worse fibrosis when challenged with asbestos, whereas in the bleomycin model they are largely protected against fibrosis. In the current study the role of RAGE in a mouse model of silica induced pulmonary fibrosis was investigated. Methodology/Principal Findings: Wild type (WT) and RAGE KO mice received a single intratracheal (i.t.) instillation of silica in saline or saline alone as vehicle control. Fourteen days after treatment mice were subjected to a lung mechanistic study and the lungs were lavaged and inflammatory cells, protein and TGF-β levels in lavage fluid determined. Lungs were subsequently either fixed for histology or excised for biochemical assessment of fibrosis and determination of RAGE proteinand mRNA levels. There was no difference in the inflammatory response or degree of fibrosis (hydroxyproline levels) in the lungs between WT and RAGE KO mice after silica injury. However, histologically the fibrotic lesions in the RAGE KO mice had a more diffuse alveolar septal fibrosis compared to the nodular fibrosis in WT mice. Furthermore, RAGE KO mice had a significantly higher histologic score, a measure of affected areas of the lung, compared to WT silica treated mice. A lung mechanistic study revealed a significant decrease in lung function after silica compared to control, but no difference between WT and RAGE KO. While a dose response study showed similar degrees of fibrosis after silica treatment in the two strains, the RAGE KO mice had some differences in the inflammatory response compared to WT mice. Conclusions/Significance: Aside from the difference in the fibrotic pattern, these studies showed no indicators of RAGE having an effect on the severity of pulmonary fibrosis following silica injury. © 2010 Ramsgaard et al

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 mu g/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5-4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6-3.8, p <0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2-3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5-6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6-9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.Peer reviewe

Effects of intra-abdominal sepsis on atherosclerosis in mice

Introduction: Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis.Methods: We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation.Results: ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2 and vascular cell adhesion molecule 1) and the adhesion assay, a functional measure of endothelial activation, were elevated at 72 hours and 120 hours in mice that underwent CLP versus sham-operations (all at P <0.05).Conclusions: Using a combination of existing murine models for atherosclerosis and sepsis, we found that CLP, a model of intra-abdominal sepsis, accelerates atheroma development. Accelerated atheroma burden was associated with prolonged systemic, endothelial and intimal inflammation and was not explained by ongoing infection. These findings support observations in humans and demonstrate the feasibility of a long-term follow-up murine model of sepsis