Explore the vast range of titles available.

Background Interferon (IFN) beta drugs have been approved for the treatment of relapsing forms of multiple sclerosis (RMS) for more than 20 years and are considered to offer a favourable benefit-risk profile. In July 2014, subcutaneous (SC) peginterferon beta-1a 125 μg dosed every 2 weeks, a pegylated form of interferon beta-1a, was approved by the EMA for the treatment of adult patients with RRMS and in August 2014 by the FDA for RMS. Peginterferon beta-1a shows a prolonged half-life and increased systemic drug exposure resulting in a reduced dosing frequency compared to other available interferon-based products in MS. In the Phase 3 ADVANCE trial peginterferon beta-1a demonstrated significant positive effects on clinical and MRI outcome measures versus placebo after one year. Furthermore, in the ATTAIN extension study, sustained efficacy with long-term treatment for nearly 6 years was shown. Main text In July 2016, an interdisciplinary panel of German and Austrian experts convened to discuss the management of side effects associated with peginterferon beta-1a and other interferon beta-based treatments in MS in daily practice. The panel was composed of experts from university hospitals and private clinics comprised of neurologists, dermatologists, and an MS nurse. In this paper we report recommendations regarding best practices for adverse event management, focussing on peginterferon beta-1a. Injection site reactions (ISRs) and influenza-like illness are the most common adverse effects of interferon beta therapies and can present a burden for MS patients leading to non-adherence and discontinuation of therapy. Peginterferon beta-1a shows improved pharmacological properties. In clinical trials, the adverse event (AE) profile of peginterferon beta-1a was similar to other interferon beta formulations. The most common AEs were mild to moderate ISRs, influenza-like illness, pyrexia, and headache. Current information on the underlying cause of skin reactions associated with SC interferon treatment, and the management strategies for these AEs are limited. In pivotal trials, ISRs were mainly characterized and classified by neurologists, while dermatologists were only rarely consulted. Conclusions This report addresses expert recommendations on the management of most relevant adverse effects related to peginterferon beta-1a and other interferon betas, based on literature and interdisciplinary experience.

Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

Background Published models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence. Methods Using logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton & Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test. Results Treating culture as reference, the rapid diagnostic test had positive predictive values of 64.8% and 54.0% in derivation and internal validation corhorts with prevalences of 2.3% and 1.7%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66%) of mecA -negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with “A” or “J” were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test’s expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score. Conclusions Given a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test’s expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method.

Few bacteria are capable of causing infections of the central nervous system (CNS), one of the most subtly shielded anatomical structures within the human body. Neisseria meningitidis is an important cause of bacterial meningitis and commonly affects otherwise healthy infants and adolescents. In contrast, Listeria monocytogenes is a cause of septicaemia and meningitis in neonates and immunocompromised adults. Dendritic cells (DCs) provide the physical link between the innate and adaptive immune system and play a crucial role in host defence against invading bacterial pathogens. The mechanisms of interaction of L. monocytogenes and N. meningitidis with DCs are entirely distinct. Whereas L. monocytogenes is readily phagocytosed by DCs by a serum-dependent mechanism, N. meningitidis is largely protected against phagocytotic uptake by its polysaccharide capsule. In addition, the pattern of secreted cytokines induced by L. monocytogenes is dominated by interleukin (IL)-12 and IL-18, capable of initiating a Th-1 response, whereas N. meningitidis induces high levels of proinflammatory cytokines. Therefore, we propose distinct functions of DCs in both types of bacterial meningitis.

Human hematopoietic stem cells (HSCs) are generated in the bone marrow and differentiate into erythrocytes, granulocytes, monocytes, megacaryocytes, and lymphocytes. HSCs may be manipulated under different conditions. Advances in cell biology result in a better understanding of the relationship between viruses/bacteria and hematopoietic cells. Microbial infections can lead to profound disturbance of hematopoiesis. Infection may augment the production of cytokines, with proliferation and differentiation of the stem cells. Alternatively, infection may lead to destruction of progenitor cells. This results in defective hematopoiesis in certain infections. Since circulating CD34+ cells represent a distinct progenitor pool responsible for seeding extramedullary sites of hematopoiesis, infected peripheral blood-derived CD34+ progenitor cells may serve to disseminate pathogens into diverse anatomic sites. Therefore, progenitor cell infection may additionally effect long-term functional consequences within extramedullary sites of lymphopoiesis. A variety of viruses have been reported to target HSCs, whereas quiescent human HSCs are fully resistant to infection by different bacteria. For susceptibility of HSCs to infectious agents pathogen–receptor interaction plays an important role in virus/bacteria tropism and pathogenesis.

On the basis of attenuated intracellular bacteria, we have developed two delivery systems for either heterologous proteins or DNA vaccine vectors. The first system utilizes attenuated strains of Gram-negative bacteria which are engineered to secrete heterologous antigens via the α-hemolysin secretion system (type I) of Escherichia coli. The second system is based on attenuated suicide strains of Listeria monocytogenes, which are used for the direct delivery of eukaryotic antigen expression vectors into professional antigen-presenting cells (APC) like macrophages and dendritic cells in vitro and can be also used in animal models.

Human hematopoietic stem cells (HSCs) are generated in the bone marrow and differentiate into erythrocytes, granulocytes, monocytes, megacaryocytes, and lymphocytes. HSCs may be manipulated under different conditions. Advances in cell biology result in a better understanding of the relationship between viruses/bacteria and hematopoietic cells. Microbial infections can lead to profound disturbance of hematopoiesis. Infection may augment the production of cytokines, with proliferation and differentiation of the stem cells. Alternatively, infection may lead to destruction of progenitor cells. This results in defective hematopoiesis in certain infections. Since circulating CD34 + cells represent a distinct progenitor pool responsible for seeding extramedullary sites of hematopoiesis, infected peripheral blood-derived CD34 + progenitor cells may serve to disseminate pathogens into diverse anatomic sites. Therefore, progenitor cell infection may additionally effect long-term functional consequences within extramedullary sites of lymphopoiesis. A variety of viruses have been reported to target HSCs, whereas quiescent human HSCs are fully resistant to infection by different bacteria. For susceptibility of HSCs to infectious agents pathogen–receptor interaction plays an important role in virus/bacteria tropism and pathogenesis.