Diagnosis of insulin autoimmune syndrome using polyethylene glycol precipitation and gel filtration chromatography with ex vivo insulin exchange.

CONTEXT: Insulin-binding antibodies may produce severe dysglycaemia in insulin-naïve patients ('insulin autoimmune syndrome' (IAS) or Hirata disease), while rendering routine insulin assays unreliable. OBJECTIVE: To assess the performance of clinically used insulin assays and an optimal analytical approach in the context of IAS. DESIGN: Observational biochemical study of selected patients with hyperinsulinaemic hypoglycaemia. PATIENTS: Three patients without diabetes with recurrent spontaneous hyperinsulinaemic hypoglycaemia and 'positive' insulin antibodies. MEASUREMENTS: A panel of clinically used insulin assays (Siemens ADVIA® Centaur, Siemens Immulite® 2000, DiaSorin LIAISON® XL, PE AutoDELFIA® and the Beckman Coulter Access® 2) were used before and after plasma dilution or polyethylene glycol (PEG) precipitation. Anti-insulin IgG antibodies were measured by Isletest™ -IAA ELISA. Gel filtration chromatography (GFC) was undertaken with and without preincubation of plasma with exogenous insulin. RESULTS: Dilution of IAS plasma with assay-specific buffer increased insulin recovery, supporting negative immunoassay interference by antibodies. PEG precipitation of IAS plasma decreased insulin recovery using all assays except the Immulite® 2000. GFC discriminated high molecular weight and monomeric insulin, while ex vivo addition of exogenous insulin to plasma increased insulin bound to antibody, thereby improving the sensitivity of detection of insulin immunocomplexes. CONCLUSIONS: Immunoprecipitation with PEG must be used with caution in screening for insulin-antibody complexes as results are assay dependent. GFC with addition of exogenous insulin can identify significant insulin immunocomplexes with enhanced sensitivity, with attendant greater clinical utility and avoidance of radiolabelled reagents.Diabetes Research & Wellness Foundation Sutherland-Earl Clinical Fellowship (Grant ID: RG68554), Wellcome Trust (Grant ID: WT098498), Medical Research Council (Grant ID: MRC_MC_UU_12012/5), National Institute for Health Research (NIHR), Cambridge Biomedical Research CentreThis is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/cen.1317

Identification of proteins found to be significantly altered when comparing the serum proteome from Multiple Myeloma patients with varying degrees of bone disease

Background: Bone destruction is a feature of multiple myeloma, characterised by osteolytic bone destruction due to increased osteoclast activity and suppressed or absent osteoblast activity. Almost all multiple myeloma patients develop osteolytic bone lesions associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Biomarkers of bone remodelling are used to identify disease characteristics that can help select the optimal management of patients. However, more accurate biomarkers are needed to effectively mirror the dynamics of bone disease activity. Results: A label-free mass spectrometry-based strategy was employed for discovery phase analysis of fractionated patient serum samples associated with no or high bone disease. A number of proteins were identified which were statistically significantly correlated with bone disease, including enzymes, extracellular matrix glycoproteins, and components of the complement system. Conclusions: Enzyme-linked immunosorbent assay of complement C4 and serum paraoxonase/arylesterase 1 indicated that these proteins were associated with high bone disease in a larger independent cohort of patient samples. These biomolecules may therefore be clinically useful in assessing the extent of bone disease. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-904) contains supplementary material, which is available to authorized users

Believing the unbelievable: the myth of Russians 'with snow on their boots' in the United Kingdom, 1914

PublishedArticle“This is an Accepted Manuscript of an article published by Taylor & Francis in Cultural and Social History on1 May 2015, available online: http://www.tandfonline.com/ 10.2752/147800414X13802176314528.”In the opening months of the First World War, a rumour spread across the United Kingdom that Russian soldiers – identified by the ‘snow on their boots’ – had landed in Scotland en route to the Western Front. Despite being relegated to history’s footnotes as a comical but meaningless episode, this article takes the rumour seriously. Unconcerned with questions of ‘truth’ (the rumour was dismissed as fantastical by late October 1914), I will argue that the real value of this story is in what it reveals about British society at the outbreak of war. The rumour emerged as the British Expeditionary Force entered its first big test of the Great War – the battle of Mons – which would result in Germany’s first great victory and resulting in thousands of casualties. As such the rumour can be interpreted as a form of ‘secular apparition’ bringing consolation to many. It was one of the ways ordinary people made sense of their newly threatening world

The future of myelodysplastic syndrome—patient priorities and outcomes that matter

BackgroundWithout a definitive curative option available to many patients, learning to live with myelodysplastic syndrome (MDS) and manage symptoms effectively becomes a priority in their care. Anaemia is an almost universal feature of MDS. Individuals suffer differently and better individualisation of care is needed. Most MDS patient information offers scant appreciation for disease heterogeneity, variable response to treatment and each patient’s likely trajectory.MethodsWe undertook a two-part, online workshop to discuss what matters most to people living with MDS. Patients generated questions about their condition which they felt should be addressed by research or change how their care is delivered. Patients voted on the importance of each topic, creating a “prioritised” list of issues.ResultsFourteen participants of varying age and experience took part raising 56 unique questions under the themes of: prognosis; end of life; treatment; supportive care; medical staff training; diagnosis and communication. These reflect the symptoms of MDS, improving quality of life (QoL) and communication.DiscussionAlthough haemoglobin (Hb) levels have correlation to QoL, it is widely reported that other factors are important in determining QoL and need for transfusions varies despite stable Hb levels. We showed that Hb level and the need for transfusions is not comparable between different patients and even non-comparable over time meaning that the maximal benefit and timing of transfusions cannot be determined from Hb alone. This workshop highlighted patient dissatisfaction with the “numbers-led” approach and the need for an alternative method to determine when to transfuse

A restrictive versus liberal transfusion strategy to prevent myocardial injury in patients undergoing surgery for fractured neck of femur:a feasibility randomised controlled trial (RESULT-NOF)

BackgroundThe optimum transfusion strategy in patients with fractured neck of femur is uncertain, particularly if there is coexisting cardiovascular disease. MethodsWe conducted a prospective, single-centre, randomised feasibility trial of two transfusion strategies. We randomly assigned patients undergoing surgery for fractured neck of femur to a restrictive (haemoglobin, 70–90 g L −1) or liberal (haemoglobin, 90–110 g L −1) transfusion strategy throughout their hospitalisation. Feasibility outcomes included: enrolment rate, protocol compliance, difference in haemoglobin, and blood exposure. The primary clinical outcome was myocardial injury using troponin estimations. Secondary outcomes included major adverse cardiac events, postoperative complications, duration of hospitalisation, mortality, and quality of life. ResultsWe enrolled 200 (22%) of 907 eligible patients, and 62 (31%) showed decreased haemoglobin (to 90 g L −1 or less) and were thus exposed to the intervention. The overall protocol compliance was 81% in the liberal group and 64% in the restrictive group. Haemoglobin concentrations were similar preoperatively and at postoperative day 1 but lower in the restrictive group on day 2 (mean difference [MD], 7.0 g L −1; 95% confidence interval [CI], 1.6–12.4). Lowest haemoglobin within 30 days/before discharge was lower in the restrictive group (MD, 5.3 g L −1; 95% CI, 1.7–9.0). Overall, 58% of patients in the restrictive group received no transfusion compared with 4% in the liberal group (difference in proportion, 54.5%; 95% CI, 36.8–72.2). The proportion with the primary clinical outcome was 14/26 (54%, liberal) vs 24/34 (71%, restrictive), and the difference in proportion was –16.7% (95% CI, –41.3 to 7.8; P=0.18). ConclusionA clinical trial of two transfusion strategies in hip fracture with a clinically relevant cardiac outcome is feasible