Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

BACKGROUND: Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients. MATERIAL AND METHODS: Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months. RESULTS: Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6–8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion. CONCLUSIONS: Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs

Resonantly enhanced nonlinear optics in semiconductor quantum wells: An application to sensitive infrared detection

A novel class of coherent nonlinear optical phenomena, involving induced transparency in quantum wells, is considered in the context of a particular application to sensitive long-wavelength infrared detection. It is shown that the strongest decoherence mechanisms can be suppressed or mitigated, resulting in substantial enhancement of nonlinear optical effects in semiconductor quantum wells.Comment: 4 pages, 3 figures, replaced with revised versio

National Early Warning Score Accurately Discriminates the Risk of Serious Adverse Events in Patients With Liver Disease.

BACKGROUND & AIMS: The National Early Warning Score (NEWS) is used to identify deteriorating adult hospital inpatients. However, it includes physiological parameters frequently altered in patients with cirrhosis. We aimed to assess the performance of the NEWS in acute and chronic liver diseases. METHODS: We collected vital signs, recorded in real time, from completed consecutive admissions of patients 16 years or older to a large acute-care hospital in Southern England, from January 1, 2010, through October 31, 2014. Using International Classification of Diseases, 10th revision, codes, we categorized patients as having primary liver disease, secondary liver disease, or none. For patients with liver disease, 2 analysis groups were developed: the first was based on clinical group (such as acute or chronic, alcohol-induced, or associated with portal hypertension), and the second was based on a summary of liver-related, hospital-level mortality indicator diagnoses. For each, we compared the abilities of the NEWS and 34 other early warning scores to discriminate 24-hour mortality, cardiac arrest, or unanticipated admission to the intensive care unit using the area under the receiver operating characteristic (AUROC) curve and early warning score efficiency curve analyses. RESULTS: The NEWS identified patients with primary, nonprimary, and no diagnoses of liver disease with AUROC values of 0.873 (95% CI, 0.860-0.886), 0.898 (95% CI, 0.891-0.905), and 0.879 (95% CI, 0.877-0.881), respectively. High AUROC values were also obtained for all clinical subgroups; the NEWS identified patients with alcohol-related liver disease with an AUROC value of 0.927 (95% CI, 0.912-0.941). The NEWS identified patients with liver diseases with higher AUROC values than other early warning scoring systems. CONCLUSIONS: The NEWS accurately discriminates patients at risk of death, admission to the intensive care unit, or cardiac arrest within a 24-hour period for a range of liver-related diagnoses. Its widespread use provides a ready-made, easy-to-use option for identifying patients with liver disease who require early assessment and intervention, without the need to modify parameters, weightings, or escalation criteria

Analysis of Bile Colonization and Intestinal Flora may Improve Management in Liver Transplant Recipients Undergoing ERCP

Background: Immunosuppression, denervation of biliary tract, and presence of biliary strictures favor colonization of bile with microorganisms after liver transplantation. Little is known about spectrum and antibiotic susceptibility of this colonization. Material and Methods: Bile and feces were collected prospectively from 38 patients who underwent endoscopic retrograde cholangiopancreaticography after liver transplantation. Samples were analyzed for colonization and antibiotic susceptibility. Results: From the 38 tested bile samples, 86.6% tested positive. Of those, 26 (78.8%) were polymicrobial. Of isolated bile samples, 52 (64.2%) were gram-positive, 22.2% were gram-negative, and 13.6% revealed Candida albicans. Most detectable gram-positive bacteria were Enterococcus faecium. Most detectable gram-negative bacteria were E. coli and Klebsiella pneumonia. Our analyses revealed high resistance rates of the isolates. Only 55.6% of isolates were sensitive to ciprofloxacin, 54% were sensitive to piperacillin/tazobactam, and 60.3% were sensitive to imipenem. High susceptibility rates were found for linezolid and vancomycin (72.9% and 72.6%, respectively). We found a high correlation between microorganisms found in bile and those isolated from stool. Conclusions: Bile of liver transplant recipients is frequently colonized with microorganisms. The starting point of this colonization is usually the intestine. Systematic analysis of bile colonization during endoscopic interventions on biliary tracts of liver transplant recipients might help to select effective prophylactic antibiotic regimes as well as to facilitate the choice of suitable antimicrobial therapy in case of septic complications

Modeling of Photoionized Plasmas

In this paper I review the motivation and current status of modeling of plasmas exposed to strong radiation fields, as it applies to the study of cosmic X-ray sources. This includes some of the astrophysical issues which can be addressed, the ingredients for the models, the current computational tools, the limitations imposed by currently available atomic data, and the validity of some of the standard assumptions. I will also discuss ideas for the future: challenges associated with future missions, opportunities presented by improved computers, and goals for atomic data collection.Comment: 17 pages, 8 figures, to appear in the proceedings of Xray2010, Utrecht, the Netherlands, March 15-17 201

A Real-Space Full Multigrid study of the fragmentation of Li11+ clusters

We have studied the fragmentation of Li11+ clusters into the two experimentally observed products (Li9+,Li2) and (Li10+,Li) The ground state structures for the two fragmentation channels are found by Molecular Dynamics Simulated Annealing in the framework of Local Density Functional theory. Energetics considerations suggest that the fragmentation process is dominated by non-equilibrium processes. We use a real-space approach to solve the Kohn-Sham problem, where the Laplacian operator is discretized according to the Mehrstellen scheme, and take advantage of a Full MultiGrid (FMG) strategy to accelerate convergence. When applied to isolated clusters we find our FMG method to be more efficient than state-of-the-art plane wave calculations.Comment: 9 pages + 6 Figures (in gzipped tar file

BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs

Background: A clinical study to investigate the leukotriene B4 (LTB4)-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients. Methods: P. aeruginosa DNA in the blood of CF patients during and after acute pulmonary exacerbations and in stable patients with non-CF bronchiectasis (NCFB) and healthy individuals was assessed by PCR. The effect of BIIL 284 treatment was tested in an agar bead murine model of P. aeruginosa lung infection. Bacterial count and inflammation were evaluated in lung and other organs. Results: Most CF patients (98%) and all patients with NCFB and healthy individuals had negative P. aeruginosa DNA in their blood. Similarly, the P. aeruginosa-infected mice showed bacterial counts in the lung but not in the blood or spleen. BIIL 284 treatment decreased pulmonary neutrophils and increased P. aeruginosa numbers in mouse lungs leading to significantly higher bacteremia rates and lung inflammation compared to placebo treated animals. Conclusions: Decreased airway neutrophils induced lung proliferation and severe bacteremia in a murine model of P. aeruginosa lung infection. These data suggest that caution should be taken when administering anti-inflammatory compounds to patients with bacterial infections

Impact of introducing an electronic physiological surveillance system on hospital mortality

YesBackground Avoidable hospital mortality is often attributable to inadequate patient vital signs monitoring, and failure to recognise or respond to clinical deterioration. The processes involved with vital sign collection and charting; their integration, interpretation and analysis; and the delivery of decision support regarding subsequent clinical care are subject to potential error and/or failure. Objective To determine whether introducing an electronic physiological surveillance system (EPSS), specifically designed to improve the collection and clinical use of vital signs data, reduced hospital mortality. Methods A pragmatic, retrospective, observational study of seasonally adjusted in-hospital mortality rates in three main hospital specialties was undertaken before, during and after the sequential deployment and ongoing use of a hospital-wide EPSS in two large unconnected acute general hospitals in England. The EPSS, which uses wireless handheld computing devices, replaced a paper-based vital sign charting and clinical escalation system. Results During EPSS implementation, crude mortality fell from a baseline of 7.75% (2168/27 959) to 6.42% (1904/29 676) in one hospital (estimated 397 fewer deaths), and from 7.57% (1648/21 771) to 6.15% (1614/26 241) at the second (estimated 372 fewer deaths). At both hospitals, multiyear statistical process control analyses revealed abrupt and sustained mortality reductions, coincident with the deployment and increasing use of the system. The cumulative total of excess deaths reduced in all specialties with increasing use of the system across the hospital. Conclusions The use of technology specifically designed to improve the accuracy, reliability and availability of patients’ vital signs and early warning scores, and thereby the recognition of and response to patient deterioration, is associated with reduced mortality in this study

Scientific Highlights of the HETE-2 Mission

The HETE-2 mission has been highly productive. It has observed more than 250 GRBs so far. It is currently localizing 25 - 30 GRBs per year, and has localized 43 GRBs to date. Twenty-one of these localizations have led to the detection of X-ray, optical, or radio afterglows, and as of now, 11 of the bursts with afterglows have known redshifts. HETE-2 has confirmed the connection between GRBs and Type Ic supernovae, a singular achievement and certainly one of the scientific highlights of the mission so far. It has provided evidence that the isotropic-equivalent energies and luminosities of GRBs are correlated with redshift, implying that GRBs and their progenitors evolve strongly with redshift. Both of these results have profound implications for the nature of GRB progenitors and for the use of GRBs as a probe of cosmology and the early universe. HETE-2 has placed severe constraints on any X-ray or optical afterglow of a short GRB. It is also solving the mystery of "optically dark' GRBs, and revealing the nature of X-ray flashes.Comment: 10 pages, 9 figures, to appear in proc. "The Restless High-Energy Universe", Royal Tropical Institute, Amsterdam; revised text, added ref