SUMMARYEfficient phagocytic clearance of apoptotic cells is crucial in many biological processes. A bewildering array of phagocyte receptors have been implicated in apoptotic cell clearance, but there is little convincing evidence that they act directly as apoptotic cell receptors. Alternatively, apoptotic cells may become opsonized, whereby naturally occurring soluble factors (opsonins) bind to the cell surface and initiate phagocytosis. Evidence is accumulating that antibodies and complement proteins opsonize apoptotic cells, leading to phagocytosis mediated by well-defined 'old-fashioned' receptors for immunoglobulin-Fc and complement. In this review we summarize the evidence that opsonization is necessary for high capacity clearance of apoptotic cells, which would render putative direct apoptotic cell receptors redundant.

SummaryUnderstanding the complex immunological consequences of red cell transfusion is essential if we are to use this valuable resource wisely and safely. The decision to transfuse red cells should be made after serious considerations of the associated risks and benefits. Immunological risks of transfusion include major incompatibility reactions and transfusion-related acute lung injury, while other immunological insults such as transfusion-related immunomodulation are relatively underappreciated. Red cell transfusions should be acknowledged as immunological exposures, with consequences weighed against expected benefits. This article reviews immunological consequences and the emerging evidence that may inform risk-benefit considerations in clinical practice.

In the community, acute hypoglycaemia is commonly caused by therapies for diabetes mellitus or the excessive consumption of alcohol. Although most episodes do not require admission to hospital, little information is available on the causes and outcome of those that do. We retrospectively surveyed adult patients admitted to a large urban teaching hospital with acute hypoglycaemia in a 12-month period, identifying 56 admissions of 51 patients. Forty-one had diabetes mellitus, 33 (80%) of whom were receiving treatment with insulin. The others had hypoglycaemia induced by excessive consumption of alcohol or by deliberate self-poisoning with insulin. A history of psychiatric illness and/or chronic alcoholism was common. Neurological manifestations of hypoglycaemia were the principal reason for admission, observed on 50 occasions (89%), and 11 events (20%) had precipitated convulsions. Although many patients (59%) had received treatment for hypoglycaemia before admission, hypoglycaemia recurred in 16% of patients in hospital. Four patients (7%) died following admission, but in only one case was this the direct result of hypoglycaemia. However, within 15 months of the index hypoglycaemia event, a further six patients (11%) had died, mostly of causes unrelated to hypoglycaemia. Patients who require hospital admission for treatment of hypoglycaemia have a high incidence of neurological manifestations, a high rate of mental illness and other medical disorders, and may represent a high-risk subgroup with a poor long-term prognosis.

BackgroundBreathlessness is distressing for patients and is a common reason for emergency department attendance. Chronic refractory breathlessness is associated with anxiety, embarrassment and fear, and effective management is essential to improve quality of life and reduce hospital admissions.1 Interventions such as breathing control, activity pacing and anxiety management are beneficial.2 This study examined the effect of attending a dedicated respiratory physiotherapist led breathlessness service on patient reported outcomes.MethodPatients attending the breathlessness clinic between April 2015 and April 2016 completed Numerical Rating Scales (NRS) out of 10 to grade their breathlessness. Data were collected before and 1–2 weeks after clinic attendance. Lower NRS scores represented a lower symptom burden. A change of 1 or more on the NRS was considered clinically significant. Responses were compared using t-tests and Wilcoxon signed-rank tests. Data are presented as mean ± SD.ResultsFifty-two patients attended the breathless clinic during the study period (mean age 73, range 49–92 years). Patients had a range of diagnoses causing their breathlessness with idiopathic pulmonary fibrosis (44.2%), lung cancer (19.2%), and non-specified interstitial lung disease (11.5%) being most common.Significant improvements were observed across all domains. Average breathlessness experienced in the past 24 hours reduced from 3.9 ± 1.7 to 3.6 ± 1.6 (p = 0.001). The worst breathlessness experienced in the past 24 hours reduced by 1 point to 6.3 ± 1.9 (p < 0.001). The distress experienced from breathlessness reduced from 5.8 ± 6.4 to 4.8 ± 4.8 (p < 0.001). Patients’ perceived ability to cope with their breathlessness improved by 1 point (p < 0.001).ConclusionsA specialist breathlessness clinic provided a valuable service for patients with chronic refractory breathlessness. Significant, clinically meaningful benefits were observed in terms of the severity of breathlessness that patients experienced. Furthermore, patients perceived a reduction in distress and increased ability to cope.ReferencesEkström M, Abernethy A, Currow D. The management of chronic breathlessness in patients with advanced and terminal illness. BMJ 2015;349:g7617.Higginson IJ, Bausewein C, Reilly C, et al. An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respiratory Medicine2014;2:979–87.

The acute presentation of alcoholic ketoacidosis accompanied by hyperglycaemia is rare, but it may lead to the misdiagnosis of metabolically decompensated Type 1 (insulin‐dependent) diabetes and to inadvertent treatment with insulin. A case of alcoholic ketoacidosis is described in which recent excessive alcohol consumption was concealed by the patient, which resulted in a diagnosis of diabetic ketoacidosis. The blood glucose concentration in alcoholic ketoacidosis may be determined by the extent to which endogenous insulin secretion is suppressed and the extent of the peripheral insulin resistance induced by alcohol and the concomitant secretion of counter‐regulatory hormones.

Based on an annual unit cost of £22, 245.96 for pirfenidone (without undisclosed discount). To date 96 patients have been treated for a total of 876 months at a total cost of £1,623,955 in two and a half years. Conclusion This study highlights both the health and economic impacts of pirfenidone over a two and a half year period of prescribing.

Introduction and objectivesHeterogeneity of idiopathic pulmonary fibrosis (IPF) means it is difficult to identify those at highest risk of progression who are most likely to benefit from treatment. A biomarker that predicts disease activity, prognosis and treatment response would be beneficial. We previously reported increased platelet reactivity in IPF,1 and here we explore whether platelet reactivity warrants further investigation as a biomarker.MethodsData were obtained from two studies: Study 1. a study of platelet reactivity in IPF; and Study 2. a pilot randomised-controlled trial of an investigational IPF treatment. Standard protocols were used to measure platelet-monocyte aggregate (PMA) formation, P-selectin expression, and fibrinogen binding in blood samples. Platelet reactivity in IPF was compared with controls. Correlation between platelet reactivity and forced vital capacity (FVC) was assessed. Study 2 data were used to assess the change in platelet reactivity in response to the intervention and correlation between baseline platelet reactivity, symptoms (KBILD) and exercise capacity (6MWD).ResultsStudy 1 included 13 IPF patients (mean± SD, Age 70.3 ± 5.8 years, 69% male, FVC 91.9 ± 17.8% predicted) and 12 controls (Age 66.2 ± 10.2, 66.7% males). Study 2 included 19 IPF patients (Age 71.5 ± 8.7, 72% males, FVC 84.4 ± 16.8% predicted). IPF patients demonstrated significantly increased platelet reactivity compared to controls (P < 0.01). Platelet reactivity and FVC did not correlate. In study 2, stimulated platelets expressed significantly less P-selectin in response to the intervention (P = 0.03). Unstimulated PMA formation moderately correlated with KBILD (r = 0.38. P = 0.01), but other platelet markers showed no correlation with symptoms or exercise capacity.ConclusionIPF patients exhibit increased platelet reactivity compared to controls. The reduction in platelet reactivity in response to an intervention may indicate responsiveness to treatment effect. Although there was no correlation between FVC and platelet activation, further investigation is warranted to assess associations between platelet reactivity and lung function decline and mortality.Reference1 Crooks MG, Fahim A, Naseem KM, Morice AH, Hart SP. Increased platelet reactivity in idiopathic pulmonary fibrosis is medicated by a plasma factor. PLoS One 2014;9(10):e111347

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