Patient-reported lower limb edema after primary radiotherapy for prostate cancer.

Background: Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patient-reported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT.

Material And Methods: A total of 302 patients with PCa with prospective registration of patient-reported LLE (EORTC QLQ-PR25 (Question 46)) were included.

The Effect of Conflicting Public Health Guidance on Smokers' and Vapers' E-cigarette Harm Perceptions.

Background: E-cigarettes are increasingly being viewed, incorrectly, as more harmful than cigarettes. This may discourage smokers from switching to e-cigarettes. One potential explanation for these increasingly harmful attitudes is conflicting information presented in the media and online, and from public health bodies.

Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections.

Background: Necrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) or Streptococcus pyogenes (mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive.

Tackling Smoker Misperceptions About E-cigarettes Using Expert Videos.

Background: The pervasive misperception that e-cigarettes are equally or more harmful than combustible cigarettes is a barrier to current smokers switching to e-cigarettes. To tackle misperceptions, public health bodies are using informational videos, although their efficacy is unknown.

Methods: In our online study, current UK smokers who do not vape (n = 382) were randomized to view either: (1) a Cancer Research UK (CRUK) text-only video; (2) a video featuring leading e-cigarette experts (expert); or (3) a no video control condition, and then completed questions regarding e-cigarette harm perceptions.

Accessing Forbidden Glass Regimes through High-Pressure Sub-T Annealing.

Density and hardness of glasses are known to increase upon both compression at the glass transition temperature (T) and ambient pressure sub-T annealing. However, a serial combination of the two methods does not result in higher density and hardness, since the effect of compression is countered by subsequent annealing and vice versa. In this study, we circumvent this by introducing a novel treatment protocol that enables the preparation of high-density, high-hardness bulk aluminosilicate glasses.

Volume and structural relaxation in compressed sodium borate glass.

The structure and properties of glass can be modified through compression near the glass transition temperature (T), and such modified structure and properties can be maintained at ambient temperature and pressure. However, once the compressed glass undergoes annealing near T at ambient pressure, the modified structure and properties will relax. The challenging question is how the property relaxation is correlated with both the local and the medium-range structural relaxation.

A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies.

Purpose: To establish and validate a rapid, cost-effective and accurate screening assay for the simultaneous testing of human naturally occurring anti-cytokine autoantibodies (c-aAb) targeting interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon α (IFNα). Because the c-aAbs can be transferred to patients through blood transfusion, the assay was used to assess c-aAb levels in a cohort of patients who were receiving blood transfusions and subsequently presented with or without febrile reactions.

Materials And Methods: The microsphere-based Luminex platform was used.

Pressure-induced changes in interdiffusivity and compressive stress in chemically strengthened glass.

Glass exhibits a significant change in properties when subjected to high pressure because the short- and intermediate-range atomic structures of glass are tunable through compression. Understanding the link between the atomic structure and macroscopic properties of glass under high pressure is an important scientific problem because the glass structures obtained via quenching from elevated pressure may give rise to properties unattainable under standard ambient pressure conditions. In particular, the chemical strengthening of glass through K(+)-for-Na(+) ion exchange is currently receiving significant interest due to the increasing demand for stronger and more damage-resistant glass.

Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease.

A 61 year old woman with active luminal Crohn's disease was successfully treated with infliximab induction therapy followed by 5 infusions every 8 weeks. However, symptoms returned in the weeks preceding the 7th and 8th infusions. The 9th infusion was therefore given only 4 weeks after the 8th infusion, but an acute severe anaphylactoid reaction occurred immediately after start of the infusion.

Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease.

Background: Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD).

Aim: To investigate the role of anti-IFX antibodies (Ab) and other risk factors.

Methods: The study included all IBD patients treated with IFX at a Danish university hospital until 2010 either continuously (IFX every 4-12 weeks) or episodically (reinitiation after >12 weeks).

Fidelity to clinical guidelines using a care pathway in the treatment of first episode psychosis.

Objective: To evaluate the implementation of clinical practice guidelines in the initial stages of treatment of first episode psychosis, through use of a care pathway within one area mental health service.

Methods: A fidelity audit was undertaken using data from local Early Psychosis Care Pathway documents, completed for the cohort of clients with early psychosis seen in the first 2 years of an integrated early psychosis programme model, at St Vincent's Mental Health Service, Melbourne, Australia.

Results: The utilisation of a care pathway greatly supported both the documentation of clinical process and fidelity to clinical guidelines in early psychosis treatment.

Preparation and validation of radio iodinated recombinant human IL-10 for the measurement of natural human antibodies against IL-10.

Radio iodinated recombinant human IL-10 was prepared and validated for the measurement of natural human anti-IL-10 antibodies. Iodination of IL-10 was accomplished by means of the chloramine-T method. The crude tracer was purified by size chromatography as homo-dimeric IL-10 with a specific activity of 75 cpm/pg.

Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis.

Background: Tumour necrosis factor alpha (TNFalpha) neutralising antibody constructs are increasingly being used to treat rheumatoid arthritis (RA).

Objective: To determine potential differences in clinical responses, soluble drug levels and antibody formation between patients with RA receiving infliximab and adalimumab.

Methods: 69 patients with RA fulfilling the 1987 American College of Rheumatology criteria and about to start treatment with infliximab or adalimumab, were enrolled consecutively.

Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies.

Objectives: Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mouse-human IgG1/kappa antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we have compared different methods of assessing drug levels and anti-infliximab antibodies (Abs) and analysed the character of these Abs in sera of RA patients treated with infliximab for 1.

Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation.

IL-6 is involved in inflammation and a therapeutic target. 0.1% of Danish blood donors have nanomolar plasma concentrations of polyclonal, picomolar affinity and in vitro as well as in vivo neutralizing IgG autoantibodies to IL-6 (aAb-IL-6).

Transfusion-related inhibition of cytokines (TRICK). Experimental transfer of neutralizing autoantibodies to interleukin-6 by plasma transfusions.

Background: For some unknown reason humans may 'spontaneously' produce high amounts of neutralizing autoantibodies to a number of growth factors and cytokines. Reaching a certain high level the antibodies render the person cytokine deficient, mostly without overt clinical manifestations. The autoantibodies in question are detectable in normal immunoglobulin preparations and correspondingly in normal human plasma for transfusion.

[Treatment of rheumatoid arthritis (RA) with anti-TNF-alpha antibody (Remicade). Individual monitoring of bioavailability and immunogenicity--secondary publication].

Remicade/infliximab is effective in rheumatoid arthritis (RA), but response failure is frequent. Sera from 106 RA patients were monitored using an RIA for functional infliximab and an RIA for anti-infliximab antibody (Ab). S-infliximab varied considerably, e.

Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab.

Objective: Infliximab, an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial. This study was undertaken to investigate whether serologic monitoring of infliximab bioavailability and immunogenicity in individual patients would be useful in optimizing treatment regimens to improve efficacy and tolerability.

Inhibition of rBet v 1-induced basophil histamine release with specific immunotherapy -induced serum immunoglobulin G: no evidence that FcgammaRIIB signalling is important.

Background: Human basophils and mast cells express the low-affinity immunoglobulin (Ig)G receptor FcgammaRIIB. It has previously been shown in artificial model systems that cross-linking of the high-affinity IgE receptor FcepsilonRI and FcgammaRIIB leads to inhibition of FcepsilonRI signalling.

Objective: The aim of the present study was to investigate whether cross-linking of FcepsilonRI and FcgammaRIIB contributes to IgG-mediated inhibition of histamine release in human basophils in a system using the sera from specific immunotherapy (SIT) patients and the major allergen from birch pollen, Bet v 1.

Is immunotherapy-induced birch-pollen-specific IgG4 a marker for decreased allergen-specific sensitivity?

Background: The role of IgG4 during allergen-specific immunotherapy (SIT) is still controversial. The available studies present paramount differences in in vitro techniques, allergens, and clinical outcome parameters. By implementing a sensitive method, and pivotal clinical outcome parameters, we wanted to ascertain the utility of IgG4 as a clinical marker of decreased allergen-specific sensitivity to a common aeroallergen.

High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors.

IL-6-specific autoantibodies (aAb-IL-6) have been reported in diseased and healthy individuals. We recently established a model for aAb-IL-6 in different mouse strains, based on vaccination with immunogenic IL-6 analogues, in which titers of aAb-IL-6 above 1,000 resulted in an in vivo IL-6 deficiency. Here, we examined aAb-IL-6 in 4,230 blood donors.

The blocking activity of birch pollen-specific immunotherapy-induced IgG4 is not qualitatively superior to that of other IgG subclasses.

Allergen-specific IgG antibodies induced by specific immunotherapy (SIT) interfere with the allergen-IgE interaction, and act as blocking antibodies in vitro. It has been hypothesised that IgG4, as opposed to other IgG subclasses, is particularly important in this function, which may play a role for the clinical efficacy of SIT. In this study, fractionated serum samples from 14 SIT-treated birch pollen allergic individuals enabled determination of the inhibitory capacity of IgG4 alone versus non-IgG4 IgG.

TNF and LT binding capacities in the plasma of arthritis patients: effect of etanercept treatment in juvenile idiopathic arthritis.

Background: Etanercept (Enbrel) induces a rapid and sustained decline in disease activity in the majority of patients with refractory juvenile idiopathic arthritis (JIA). For unknown reasons, however, a number of JIA patients fail to respond to this therapy. During this treatment neutralisation of tumour necrosis factor (TNF, previously termed TNF alpha) and lymphotoxin (LT, previously termed TNF beta) may be mediated by etanercept itself as well as by naturally occurring soluble TNF receptors.

Knocking out IL-6 by vaccination.

Inappropriate expression of IL-6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL-6-receptor interactions. Here we present a simple and highly effective approach based on vaccination with a pool of specifically mutated IL-6 analogues to induce a neutralizing IL-6 antibody response in mice.