Musculoskeletal symptoms and non-prescribed treatments are common in an urban African population of people living with HIV.

There are no data from West Africa reporting musculoskeletal (MSK) disease in people living with HIV (PLWH). Our primary outcome was to measure the prevalence of MSK symptoms in PLWH in urban West Africa. Our secondary outcomes were to describe the disability, impact on work and treatment use associated with the presence of MSK pain. We conducted an e-questionnaire-based point prevalence study of musculoskeletal symptoms, associated disability and treatment in 292 PLWH attending routine follow-up in Lagos, Nigeria. Seventy-three (25%) patients reported MSK pain; 28 (38%) reported chronic symptoms (> 3 months). HIV suppression rates were high in this population (n = 240, 82%) and comparable between individuals with and without chronic pain. MSK pain was associated with female gender and higher body mass index (BMI). Mechanical pain was the most common pain syndrome identified (n = 34, 47%). Lumbar spine and knee were the most common sites. Chronic pain was associated with increased disability compared with the presence of any MSK pain. High rates of treatment-seeking behaviour were seen in those individuals reporting MSK pain (n = 62, 85%). The majority of these individuals sought traditional treatments (n = 48, 66%). Chronic MSK pain and non-prescribed treatments are common in PLWH established on ART in urban West Africa. Studies are required to measure the long-term impact of these symptoms and medicines on retention in HIV care and ART adherence, besides other long-term health outcomes.

Intravenous immunogobulin therapy for severe gastrointestinal involvement in systemic sclerosis.

OBJECTIVES: Gastrointestinal (GI) disease is one of the major causes of morbidity in patients with systemic sclerosis (SSc). The most common manifestation of GI disease is oesophageal involvement affecting 70-90% of patients. Severe GI disease is uncommon, but results in symptoms such as early satiety, pseudo-obstruction, weight loss and malnutrition. The pathogenesis is relatively poorly understood, and management focuses on symptomatic control rather than immunomodulation. METHODS: We describe two cases of patients with SSc myositis overlap syndrome with severe GI involvement who demonstrated improvements in swallowing, early satiety and diarrhoea following the administration of intravenous immunoglobulin (IVIg). RESUTS: Clinical data related to the two cases were collected by review of medical records. CONCLUSIONS: GI complications range from mild symptoms to debilitating and life threatening. We propose that IVIg may have an immunomodulatory effect in a subset of patients with SSc myositis overlap syndrome.

Simulation training for acute medical specialist trainees: a pilot.

Simulation training is a method of interactive teaching and training for healthcare professionals. Medical education research demonstrates that high fidelity simulation leads to effective learning. Acute Medical Specialist Year Three-plus Trainee (ST3+) doctors are often required to manage high-pressure situations, requiring a combination of clinical and non-clinical abilities. We therefore hypothesised that simulation training could be an ideal training tool for this cohort. We designed a simulation training day for ST3+trainees which exposed them to ethically challenging scenarios. The learning objectives were mapped to the acute medical curriculum, focusing on areas trainees may traditionally describe as either difficult to achieve, or for those for which providing evidence may be challenging. Simulation scenarios and debriefing sessions enabled trainees to explore different views in a protected environment, and feedback was strongly positive. We strongly recommend simulation training as a teaching tool for Acute Medical ST3+ doctors.

Systemic sclerosis in pregnancy.

Systemic sclerosis is a rare multisystem connective tissue disease. It predominantly affects women and poses a significant risk to mother and baby during pregnancy if not managed appropriately. The commonest manifestations are skin fibrosis and Raynaud's phenomenon. Subgroups of women have an increased risk of organ involvement, especially interstitial lung disease, pulmonary arterial hypertension and renal crises. Pregnancy increases the risk to the mother, especially those with established organ involvement, but also the development of new organ dysfunction; and risks to the fetus. Optimising these women prior to conception, along with careful management and surveillance during pregnancy, is vital for optimising pregnancy outcome. Women with scleroderma need to be managed in a specialised centre with coordinated care from the multi-disciplinary teams including physicians, obstetricians, anaesthetists, neonatologists and midwives. This review aims to describe the risks associated with systemic sclerosis and pregnancy, with management advice for physicians looking after pregnant women with this chronic condition.

Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration.

Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.

Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

INTRODUCTION: Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients. METHODS: Dermal interstitial fluid sample from the involved forearm skin, and synchronous plasma samples were collected from SSc patients (n = 26, diffuse cutaneous SSc (DcSSc) n = 20, limited cutaneous SSc (LcSSc) n = 6), and healthy controls (HC) (n = 10) and profiled by Luminex® array for inflammatory cytokines, chemokines, and growth factors. RESULTS: Luminex® profiling of the dermal blister fluid showed increased inflammatory cytokines (median interleukin ( IL)-6 in SSc 39.78 pg/ml, HC 5.51 pg/ml, p = 0.01, median IL-15 in SSc 6.27 pg/ml, HC 4.38 pg/ml, p = 0.03), chemokines (monocyte chemotactic protein (MCP)-3 9.81 pg/ml in SSc, 7.18 pg/ml HC, p = 0.04), and profibrotic growth factors (platelet derived growth factor (PDGF)-AA 10.38 pg/ml versus 6.94 pg/ml in HC, p = 0.03). In general dermal fluid and plasma cytokine levels did not correlate, consistent with predominantly local production of these factors within the dermal lesions, rather than leakage from the serum. In hierarchical clustering and network analysis IL-6 emerged as a key central mediator. CONCLUSIONS: Our data confirm that an immuno-inflammatory environment and aberrant vascular repair are intimately linked to fibroblast activation in lesional skin in SSc. This non-invasive method could be used to profile disease activity in the clinic, and identifies key inflammatory or pro-fibrotic proteins that might be targeted therapeutically. Distinct subgroups of SSc may be defined that show innate or adaptive immune cytokine signatures.