Biological therapies in the treatment of inflammatory disease and cancer: impact on pulmonary infection.

Biological therapies are increasingly used for the treatment of inflammatory conditions in the realms of rheumatology, dermatology, and gastroenterology due to their ability to target specific cytokines in the inflammatory cascade. The impact of these biologic therapies is immunosuppression leading to an increased risk of infection. This review focuses on commonly used biologic agents in the treatment of inflammatory conditions and cancer and their impact on pulmonary infections. We have summarized potential pathogens in this group of patients. The hope being that this will increase awareness and therefore prevention timely diagnosis and successful treatment of patients receiving biologic therapies. It is also important to note that it is not solely the choice of an agent that predisposes to particular infections. Concomitant factors that might increase an individuals' risk of contracting an infection include the underlying disease, comorbid diseases, increased age, and other medical treatment as well as exposure to opportunistic pathogens. In the treatment of cancers many immunotherapies are being developed. The most notable adverse effects from immunotherapy are due to stimulation of the immune response, and these may mimic infection by causing flu-like symptoms and breathlessness due to pneumonitis. The treatment of this is immunosuppression, further leading to an increased risk of infection. Biologic therapies have been a revolution in the treatment of inflammatory conditions and cancers. They have improved outcomes and quality of life for patients. However, the use of these drugs needs to be balanced against the risk of infection and every patient needs to be assessed on an individual basis

Mikis Theodorakis and the articulation of modern Greek identity

Drawing on contemporary identity theories, such as those of Martin Stokes and Simon Frith, my aim, in this research report, is to interrogate the construction of modern Greek identity in Theodorakis’ music. In Chapter One, I unpack the complex webs spun by history and culture to shape the modern nation, and the ways in which Theodorakis’ political and musical life have intersected with them in the twentieth century. In Chapter Two I discuss the establishment of the Popular Art Song as a powerful agent of modern Greek identity. Chapter Three examines major moves in Theodorakis’ advancing of popular art forms and hence his own renegotiation of modern Greek identity, while discussing theatre, `metasymphonic’ music and lyric tragedy. Chapter Four explores Theodorakis’ inner world, beliefs and perspectives, in particular his theory of Universal Harmony. Chapter Five discusses the phenomenon of Theodorakis’ Zorba as the allencompassing representation of modern Greek identity. It is concluded that Theodorakis shaped modern Greek identity through his music, mainly in the sixties; however, with the thrust of the technological revolution, a new Greek identity has emerged with which Theodorakis’ music cannot contend. He has nevertheless remained a Greek cultural symbol, and an international symbol of culture, peace and freedom. Ironically, his most commercial piece, ‘Zorba’s Dance’ from the film Zorba the Greek, has become an international marker of Greek identity

Biologic therapies for systemic lupus erythematosus: where are we now?

Advances in molecular biology have led to the development of biologic therapies. This is particularly relevant in systemic lupus erythematosus (SLE), which is a multisystem autoimmune rheumatic disease (ARD) associated with potentially life-threatening complications if not adequately treated. The availability of new biologic drugs has improved the prognosis of SLE in selected cases associated with unsatisfactory response to conventional therapies. Over the last decade, there have been developments in the availability of biologic agents for SLE treatment based upon the advances in the understanding of the disease pathogenesis. Even if the evidence of biologic treatment efficacy in SLE is weaker than in other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA), significant progress was made, as the first biologic treatment for use in SLE patients received approval in 2011. These new biologic therapies for SLE range from anti-CD20/CD22 (clusters of differentiation characteristic to B cells), to anti-B cell activating factors and anti-interferon alpha (IFNα). This chapter reviews the various biologic agents used in SLE, their mechanism of action and safety profile. The most common side effects to biologic treatments include infection, tuberculosis (TB) reactivation and allergic reactions. Less common side effects include development of lymphoma and anti-drug or autoimmune antibody formation. Despite their toxicity profile, biologic agents are gaining ground in clinical practice due to the limited efficacy or increased toxicity of conventional disease modifying agents (DMARD’s). Biologic therapies targeting B cells, such as rituximab, and B cell activation factors, such as belimumab, are currently used in the treatment of refractory SLE. Furthermore, aggressive treatment, including the use of biologic agents, reduces long-term complications associated with prolonged use of steroids in SLE, such as cardiovascular disease and osteoporosis. In the short term, the biologic agents are expensive when compared to traditional DMARDs; however there is evidence that their use is associated with long term benefits for patients with SLE, such as reduced hospital admission and disease complications, and improved patient outcomes. This chapter provides a summary of most biologic agents tested in SLE patients, considering their efficacy and safety profile, as well as the health implications associated with their use. We also take a brief look at newer agents currently investigated in clinical trials

Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis

Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation

Hypovitaminosis D among rheumatology outpatients in clinical practice.

OBJECTIVES: A role for vitamin D in the pathogenesis of autoimmune and inflammatory diseases is emerging. We undertook an audit of 25-hydroxyvitamin D (25OHD) investigation and treatment in rheumatology outpatients. METHODS: Serum 25OHD requests were matched to electronic medical records from rheumatology and metabolic bone clinics (April 2006-March 2007). Data were analysed separately for two groups, 'Documented osteoporosis/osteopaenia' (Group 1) and 'General rheumatology outpatients' (Group 2, sub-divided by diagnosis). Hypovitaminosis D was defined by 25OHD levels <50 nmol/l. Values were compared with healthy adults to calculate geometric z-scores. RESULTS: A total of 263 patients were included (Group 1, n = 122; Group 2, n = 141) with an overall median 25OHD of 44 nmol/l. The 25OHD level among general rheumatology patients (median 39 nmol/l, mean z score -1.2, was statistically significantly lower than among osteoporotic/osteopaenic patients (median 49 nmol/l, mean z score of -0.9, p < 0.05 for the difference). 25OHD was lower in inflammatory arthritis and chronic pain/fibromyalgia than in other groups. Prescribing was recorded in 100 in Group 1 (of whom 95% were prescribed calcium/800 IU cholecalciferol) and 83 in Group 2 (91% calcium/800 IU). Only 31% of the patients with 25OHD <50 nmol/l would have been identified using general guidelines for screening patients at 'high risk' of hypovitaminosis D. CONCLUSIONS: Improved guidelines for managing hypovitaminosis D in rheumatology patients are needed. We found a high prevalence of hypovitaminosis D among secondary care patients in rheumatology and widespread supplementation with 800 IU cholecalciferol. Substantially reduced levels of serum 25OHD were identified among patients with inflammatory arthritis and chronic pain

Clinical features of rheumatoid arthritis

Rheumatoid arthritis (RA) is a multiorgan chronic inflammatory condition that affects >430,000 people in the UK, constituting approximately 0.84% of the UK population. The cardinal clinical feature is a symmetrical polyarthritis that predominantly affects the small joints. RA can affect other components of the musculoskeletal system (bursitis, tendinopathy, muscle atrophy, osteoporosis) and almost every organ in the body. Extra-articular manifestations of RA can be cutaneous, haematological, neurological, pulmonary, cardiac, renal and ocular. A better understanding of the varied clinical aspects of RA is vital to instigating appropriate management. This review provides a detailed description of the clinical manifestations of RA, both musculoskeletal and extra-articular

Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence

There is limited evidence relating to the impact of disease modifying anti-rheumatic drugs (DMARDs) upon male fertility and peri-conception paternal exposure in men with rheumatic disease. Therefore, we conducted a systematic review of available evidence to update information on this subject and guide paternal counselling. A systematic search of PubMed and Embase was carried out up to September 2017, to find relevant peer-reviewed papers, using keywords for fertility/spermatogenesis/conception, men, and disease modifying or biologic drugs commonly prescribed in patients with rheumatic disease. The search yielded 724 papers, and the titles/abstracts were screened independently by 2 authors, duplicates removed and 233 potentially relevant papers selected for full text review. A total of 84 papers were included in the final analysis which covered the impact on fertility of over 611 male exposures to relevant drugs, and over 5986 pregnancies conceived during paternal exposure to (or within 3 months of stopping) these drugs. Aside from the known adverse impact of cyclophosphamide and sulfasalazine on spermatogenesis, overall there was no firm evidence of harm to fertility or pregnancy outcomes with paternal exposure to anti-TNF therapies, abatacept, rituximab, azathioprine, cyclosporine A, hydroxychloroquine, leflunomide, methotrexate or mycophenolate mofetil. There was no evidence found pertaining to the effects of male exposure to IVIG, tacrolimus, golimumab, anakinra or belimumab on fertility or pregnancy outcomes. These results provide further reassurance as to the safety of many DMARDs for men trying to conceive and will be useful when counselling men about risks of anti-rheumatic drugs to fertility and pregnancies, and following accidental conception