BackgroundThe perioperative module of the Australian Patient Blood Management guidelines recommended preoperative iron therapy for surgical patients with, or at risk of, iron deficiency anaemia. After implementing a preoperative haemoglobin optimization programme in our institution, an audit was undertaken to evaluate the benefit of preoperative iron therapy in ‘real world’ clinical practice.MethodsElective major surgery patients assessed in surgical pre‐admission clinics from 1 July 2013 to 30 June 2014 were screened for iron deficiency and anaemia. Those who were iron deficient (ferritin <30 μg/l), regardless of haemoglobin level, received either daily oral iron supplementation until day of surgery or intravenous iron polymaltose 1 g preoperatively (intervention group). Control patients who were not iron deficient were matched to the intervention group using propensity scores based on age, sex and surgical unit. The primary end‐point was the proportion of patients requiring perioperative red cell transfusion in intervention and control groups.ResultsOne hundred and fourteen patients (8·75%) had iron deficiency. Ninety‐three patients received preoperative iron therapy, 17 (18·3%) of whom required red cell transfusions postoperatively. Of the 332 control patients, 71 (21·4%) required red cell transfusion. After adjusting for preoperative haemoglobin and time from screening to surgery, the odds of red cell transfusion were significantly lower in the intervention group compared to controls (odds ratio: 0·512, 95% confidence interval: 0·268–0·977; P = 0·04).ConclusionPreoperative iron therapy was associated with reduced need for postoperative red blood cell transfusion in elective major surgery patients who were initially iron deficient.

Aims Chronic central serous chorioretinopathy (CSCR) is poorly understood. Fluid accumulates in the subretinal space and retinal pigment epitheliopathy and neurosensory atrophy may develop. Permanent vision loss occurs in approximately one third of cases. There are no effective treatments for CSCR. Recent studies have shown the mineralocorticoid receptor antagonist, eplerenone, to be effective in resolving subretinal fluid and improving visual acuity. This trial aims to compare the safety and efficacy of eplerenone in patients with CSCR in a double-masked randomised placebo-controlled trial. Methods Patients are randomised 1:1 to receive eplerenone with usual care or placebo with usual care for 12 months; 25 mg per day for 1 week, then 50 mg per day up to 12 months (unless discontinued for safety or resolution of CSCR). Key eligibility criteria are: age 18–60 years, one eye with CSCR for ≥4 months duration, best-corrected visual acuity (BCVA) >53 and <86 letters and no previous treatment. The primary outcome is BCVA at 12 months. Secondary outcomes include resolution of subretinal fluid, development of macular atrophy, subfoveal choroidal thickness, changes in low luminance visual acuity, health-related quality of life and safety. Conclusions Recruitment is complete but was slower than expected. We maintained the eligibility criteria to ensure participants had ‘true’ CSCR and recruited additional centres. Effective distribution of the investigational medicinal product (IMP) was achieved by implementing a database to manage ordering and accountability of IMP packs. The results will provide adequately powered evidence to inform clinical decisions about using eplerenone to treat patients with CSCR.

Aims/hypothesis Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. Methods Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic ( n =15), non-diabetic islet autoantibody-positive ( n =5), recent-onset (≤1.5 years duration) type 1 diabetes ( n =13), and longer-duration type 1 diabetes ( n =15). Staining for CD3, CD20 and Ki67 was used to detect primary and secondary (germinal centre-containing) follicles and CD21 and CD35 to detect follicular dendritic cell networks. Results The frequency of secondary follicles was lower in the recent-onset type 1 diabetes group compared with the non-diabetic control group. The presence of insulitis (as evidence of ongoing beta cell destruction) and diagnosis of type 1 diabetes at a younger age, however, did not appear to be associated with a lower frequency of secondary follicles. A higher proportion of primary B cell follicles were observed to lack follicular dendritic cell networks in the recent-onset type 1 diabetes group. Conclusions/interpretation Histological analysis of rare PLNs from individuals with type 1 diabetes suggests a previously unrecognised phenotype comprising decreased primary B cell follicle frequency and fewer follicular dendritic cell networks in recent-onset type 1 diabetes.

Type 1 diabetes (T1D) results from a T cell–mediated destruction of pancreatic β-cells following the infiltration of leukocytes (including CD8+, CD4+, and CD20+ cells) into and around pancreatic islets (insulitis). Recently, we reported that two distinct patterns of insulitis occur in patients with recent-onset T1D from the U.K. and that these differ principally in the proportion of infiltrating CD20+ B cells (designated CD20Hi and CD20Lo, respectively). We have now extended this analysis to include patients from the Network for Pancreatic Organ Donors with Diabetes (U.S.) and Diabetes Virus Detection (DiViD) study (Norway) cohorts and confirm that the two profiles of insulitis occur more widely. Moreover, we show that patients can be directly stratified according to their insulitic profile and that those receiving a diagnosis before the age of 7 years always display the CD20Hi profile. By contrast, individuals who received a diagnosis beyond the age of 13 years are uniformly defined as CD20Lo. This implies that the two forms of insulitis are differentially aggressive and that patients with a CD20Hi profile lose their β-cells at a more rapid rate. In support of this, we also find that the proportion of residual insulin-containing islets (ICIs) increases in parallel with age at the onset of T1D. Importantly, those receiving a diagnosis in, or beyond, their teenage years retain ∼40% ICIs at diagnosis, implying that a functional deficit rather than an absolute β-cell loss may be causal for disease onset in these patients. We conclude that appropriate patient stratification will be critical for correct interpretation of the outcomes of intervention therapies targeted to islet-infiltrating immune cells in T1D.

The islets of Langerhans play a critical role in glucose homeostasis. Islets are predominantly composed of insulin-secreting beta cells and glucagon-secreting alpha cells. In type 1 diabetes, the beta cells are destroyed by autoimmune destruction of insulin producing beta cells resulting in hyperglycemia. This is a gradual process, taking from several months to decades. Much of the beta cell destruction takes place during a silent, asymptomatic phase. Type 1 diabetes becomes clinically evident upon destruction of approximately 70-80 % of beta cell mass. Studying the decline in beta cell mass and the cells which are responsible for their demise is difficult as pancreatic biopsies are not feasible in patients with type 1 diabetes. The relative size of islets and their dispersed location throughout the pancreas means in vivo imaging of human islets is currently not manageable. At present, there are no validated biomarkers which accurately track the decline in beta cell mass in individuals who are at risk of developing, or have already developed, type 1 diabetes. Therefore, studies of pancreatic tissue retrieved at autopsy from donors with type 1 diabetes, or donors with high risk markers of type 1 diabetes such as circulating islet-associated autoantibodies, is currently the best method for studying beta cells and the associated inflammatory milieu in situ. In recent years, concerted efforts have been made to source such tissues for histological studies, enabling great insights to be made into the relationship between islets and the inflammatory insult to which they are subjected. This article describes in detail, a robust immunohistochemical method which can be utilized to study both recent, and archival human pancreatic tissue, in order to examine islet endocrine cells and the surrounding immune cells.

In the article listed above, there are two errors in the research design and methods section. In the section with the heading “Studies on Islet-Infiltrating Leukocytes,” the antibody listed as #M0701 should be attributed to Dako and not to Abcam and the Abcam rabbit anti-CD8 catalogue number should read #ab4055 and not #GR404-4. The online version reflects these changes.

Geochemical data are presented for the kimberlitic Holocene Igwisi Hills volcanoes (IHV), Tanzania, which preserve extra-crater lavas and pyroclastic rocks. Their young age and exceptional preservation enable investigation of kimberlite magma compositions and alteration pathways of kimberlites. The IHV lavas have a variable matrix assemblage dominated by calcite, olivine and a serpentine-like mineral (termed serpentine-X). Minor primary groundmass phases include apatite, phlogopite, monticellite, perovskite and spinel representing late-stage crystalisation. Secondary phases include hydrogarnet, a mixed-layer chlorite–vermiculite–montmorrilonite, minor brucite and low-temperature oxides and clays such as goethite and jamborite. The matrix of pyroclastic rocks is dominated by calcite with fewer groundmass phases. The parental magmas are inferred to have had ~21wt.% SiO2, ~22wt.% CaO, ~23wt.% MgO and Mg# ~70. The IHV are classified as calcite kimberlites. The total volatile concentrations of the primary melt are ~14wt.%, which predominantly consists of CO2 although the H2O content is also high. Whole-rock geochemical analyses indicate minor crustal contamination, low-temperature alteration and weathering. Pervasive serpentinisation in both lavas and pyroclastic rocks results from low-temperature alteration induced by the circulation of meteoric waters during cooling. Serpentine-X is potentially a new mineral and is richer in Al2O3 and FeO and poorer in SiO2 than published analyses of serpentine minerals. These compositions are attributed to a 1:2 mixture of serpentine and hydrotalcite. We propose that serpentine-X has replaced a reactive, late stage residual silicate glass, the existence of which helps explain the presence of vesicular scoria (similar to glassy basaltic pyroclasts) and viscous kimberlite lavas.

Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of β-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ–positive, multiautoantibody-positive) and partially regulated (interleukin-10–positive, pauci-autoantibody–positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed “hyper-immune CD20Hi” and “pauci-immune CD20Lo.” Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies.