A large multicentre, randomized, double-blind, cross-over study in healthy volunteers to compare pharmacokinetics, pharmacodynamics and safety of a pegfilgrastim biosimilar with its US- and EU-reference biologics.

Aims: Recombinant PEGylated human granulocyte colony-stimulating factor (pegfilgrastim) is indicated for the reduction of chemotherapy-induced neutropenia and prevention of febrile neutropenia. Biosimilar pegfilgrastim is expected to reduce the financial burden of this complication of chemotherapy. The aim of this study was to demonstrate biosimilarity between Sandoz biosimilar pegfilgrastim and its US- and EU-approved reference biologics.

Safety analysis of proposed pegfilgrastim biosimilar in Phase I and Phase III studies.

This analysis compares safety data for Sandoz proposed biosimilar (LA-EP2006) and reference pegfilgrastim from a Phase I pharmacokinetic/pharmacodynamic study in healthy volunteers (HVs) and two Phase III confirmatory studies in patients with breast cancer (BC; total n = 808). Baseline characteristics were summarized, and event rates of bone pain and headache calculated. HVs in the Phase I pharmacokinetic/pharmacodynamic study were generally younger, with lower mean body mass index, versus BC patients in PROTECT-1/-2.

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.

Objective: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients.

Study Selection: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included.

Data Sources: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421).

Clinical Chemistry Reference Intervals for C57BL/6J, C57BL/6N, and C3HeB/FeJ Mice (Mus musculus).

Although various mouse inbred strains are widely used to investigate disease mechanisms and to establish new therapeutic strategies, sex-specific reference intervals for laboratory diagnostic analytes that are generated from large numbers of animals have been unavailable. In this retrospective study, we screened data from more than 12,000 mice phenotyped in the German Mouse Clinic from January 2006 through June 2014 and selected animals with the genetic background of C57BL/6J, C57BL/6N, or C3HeB/FeJ. In addition, we distinguished between the C57BL/6NTac substrain and C57BL/6N mice received from other vendors.

Acid Sphingomyelinase Promotes Endothelial Stress Response in Systemic Inflammation and Sepsis.

The pathophysiology of sepsis involves activation of acid sphingomyelinase (SMPD1) with subsequent generation of the bioactive mediator ceramide. We herein evaluated the hypothesis that the enzyme exerts biological effects in endothelial stress response. Plasma-secreted sphingomyelinase activity, ceramide generation and lipid raft formation were measured in human microcirculatory endothelial cells (HMEC-1) stimulated with serum obtained from sepsis patients.

Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach.

Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated.

Impact of antibiotic treatment intensity on long-term sepsis-associated kidney injury in a polymicrobial peritoneal contamination and infection model.

Background/aims: Long-term kidney affections after sepsis are poorly understood. Animal models for investigating kidney damage in the late phase of disease progression are limited. The aim of this study was to investigate the impact of two antibiotic regimes on persistence of kidney injury after peritonitis.

Impact of plasma histones in human sepsis and their contribution to cellular injury and inflammation.

Introduction: Circulating histones have been identified as mediators of damage in animal models of sepsis and in patients with trauma-associated lung injury. Despite existing controversies on actual histone concentrations, clinical implications and mechanism of action in various disease conditions, histone levels in human sepsis, association with disease progression and mediated effects on endothelial and immune cells remain unreported. This study aimed to determine histone levels and its clinical implication in septic patients and to elucidate histone-mediated effects ex-vivo.

Renal outcome after vancomycin treatment and renal replacement therapy in patients with severe sepsis and septic shock: a retrospective study.

Purpose: Acute kidney injury during systemic infections is common; however, renal outcome is poorly investigated. The increase of multiresistant pathogens leads to the use of potential nephrotoxic antibiotics as vancomycin. We investigated the impact of vancomycin and renal replacement therapy (RRT) for renal recovery during sepsis.

Potential effect of physiotherapeutic treatment on mortality rate in patients with severe sepsis and septic shock: a retrospective cohort analysis.

Purpose: The aim of the study was to examine the onset and frequency of physiotherapeutic interventions (PTI) and their potential effects on the intensive care unit (ICU) mortality rate in patients with severe sepsis or septic shock.

Material And Methods: Retrospective data analysis. Univariate and multivariate Cox proportional-hazards regression analyses were performed.

Novel approach for bacteremia detection in patients with end-stage renal failure undergoing hemodialysis.

Severe systemic infections are one of the leading causes of death in patients with end-stage renal disease and are often associated with hospitalization. Since bacteria can be identified in used hemofilters in an ICU setting, it was investigated whether this method might be useful in patients undergoing regular intermittent hemodialysis. By analyzing used hemodialyzers in (n = 13) patients, we identified systemic bacteremia in two patients (15.

Physical exercise induces specific adaptations resulting in reduced organ injury and mortality during severe polymicrobial sepsis.

Objectives: High physical activity levels are associated with wide-ranging health benefits, disease prevention, and longevity. In the present study, we examined the impact of regular physical exercise on the severity of organ injury and survival probability, as well as characteristics of the systemic immune and metabolic response during severe polymicrobial sepsis.

Design: Animal study.

Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients.

Analyzing medical records of 979 patients with severe sepsis or septic shock provided some evidence that the use of low-dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) was associated with decreased hospital mortality. However, the benefit was abolished when aspirin and NSAIDs were given together.

Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on the outcome in patients with severe sepsis or septic shock.

Sepsis and its sequelae of multiple organ failure is one of the leading causes of death in the industrial countries. Several studies have shown that patients who are treated with low-dose acetyl salicylic acid (ASA) for secondary prevention of atherothrombosis may have a lower risk to develop organ failure in the case of critical illness. The benefit of ASA is probably due to an inhibition of platelet activation as well as an increase in the formation of anti-inflammatory lipoxin A4.

Persistent Chlamydia trachomatis infection of HeLa cells mediates apoptosis resistance through a Chlamydia protease-like activity factor-independent mechanism and induces high mobility group box 1 release.

Intracellular persistence of Chlamydia trachomatis has been implicated in the development of chronic infection that can result in pelvic inflammatory disease and tubal sterility. By inhibition of host cell apoptosis, chlamydiae have evolved a strategy to maintain the intracellular environment for replication and persistence. Both antiapoptotic host cell-derived factors and the chlamydial protease-like activity factor (CPAF) are involved in Chlamydia-mediated apoptosis resistance.

The late phase of sepsis is characterized by an increased microbiological burden and death rate.

Introduction: Recent models capturing the pathophysiology of sepsis and ex-vivo data from patients are speculating about immunosuppression in the so-called late phase of sepsis. Clinical data regarding survival and microbiological burden are missing. The aim of this study was to determine the clinical significance of the 'late phase' of sepsis with respect to overall survival and occurrence of microbiological findings.

Cell-derived microparticles promote coagulation after moderate exercise.

Unlabelled: Cell-derived procoagulant microparticles (MP) might be able to contribute to exercise-induced changes in blood hemostasis.

Purposes: This study aimed to examine (i) the concentration and procoagulant activity of cell-derived MP after a moderate endurance exercise and (ii) the differences in the release, clearance, and activity of MP before and after exercise between trained and untrained individuals.

Methods: All subjects performed a single bout of physical exercise on a bicycle ergometer for 90 min at 80% of their individual anaerobic threshold.

HES 130/0.4 impairs haemostasis and stimulates pro-inflammatory blood platelet function.

Introduction: Hydroxyethyl starch (HES) solutions are widely used for volume replacement therapy but are also known to compromise coagulation, impair renal function and increase long-term mortality. To test the hypotheses that HES 130/0.4 has fewer adverse effects than HES 200/0.