The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study

OBJECTIVE: The purpose of this study was to determine whether Hu23F2G (LeukoArrest), an antibody to the CD11/CD18 integrin receptors, would reduce infarct size in patients undergoing primary angioplasty for an acute myocardial infarction. BACKGROUND: Reperfusion injury in acute myocardial infarction has been shown experimentally to be related to neutrophil accumulation. Inhibitors of the CD11/CD18 or CD18 integrin receptors have been shown to reduce infarct size in experimental models. METHODS: Patients within 6 h of onset of chest pain with ST-segment elevation were randomized to receive either 0.3 mg/kg or 1.0 mg/kg of Hu23F2G or placebo just before angioplasty of occluded arteries (Thrombolysis in Myocardial Infarction TIMI flow grade 0 or 1). The primary end point was infarct size as measured by sestamibi single-photon emission computed tomography (SPECT) scan five to nine days later. RESULTS: Four-hundred and twenty patients were enrolled and received a placebo or the study drug. The groups did not differ in baseline or angiographic characteristics or angioplasty results. Infarct size was 16%, 17.2% and 16.6%, for placebo, 0.3 mg/kg and 1.0 mg/kg, respectively, of the left ventricle (p = NS). No differences were evident in those patients with anterior myocardial infarction or those presenting within 2 h of onset of chest pain. Corrected TIMI frame count was also not different between groups. Clinical events at 30 days were very low, with a mortality of 0.8%, 1.4% and 3.3%, respectively. The drug was well tolerated, with a slight increase in minor infections in the high dose group. CONCLUSIONS: The results of this multicenter, double-blind, placebo-controlled, randomized clinical trial demonstrated that an antibody to CD11/CD18 leukocyte integrin receptor did not reduce infarct size in patients who underwent primary angioplasty.     

Fibrous dysplasia of bone: craniofacial and dental implications

Fibrous dysplasia (FD) is a rare bone disease caused by postzygotic somatic activating mutations in the GNAS gene, which lead to constitutive activation of adenylyl cyclase and elevated levels of cyclic AMP, which act on downstream signaling pathways and cause normal bone to be replaced with fibrous tissue and abnormal (woven) bone. The bone disease may occur in one bone (monostotic), multiple bones (polyostotic), or in combination with hyperfunctioning endocrinopathies and hyperpigmented skin lesions (in the setting of McCune–Albright Syndrome). FD is common in the craniofacial skeleton, causing significant dysmorphic features, bone pain, and dental anomalies. This review summarizes the pathophysiology, clinical findings, and treatment of FD, with an emphasis on the craniofacial and oral manifestations of the disease.     

A prospective cohort study of risk prediction in simultaneous pancreas and kidney transplantation

IntroductionCurrent risk prediction scoring systems in pancreas transplantation are limited to organ factors and are specific to predicting graft outcome. They do not consider recipient factors or inform regarding recipient morbidity. The aim of this study was to assess the utility of commonly used general surgical risk prediction models (P-POSSUM [Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity], MODS [multiple organ dysfunction score], Charlson co-morbidity index, revised cardiac risk index, ASA [American Society of Anesthesiologists] grade and Waterlow score), and to correlate them with total length of hospital stay (LOS) and critical care unit (CCU) LOS, important surrogate markers of patient outcome.MethodsAll risk prediction scores were calculated prospectively for all simultaneous pancreas and kidney (SPK) transplant recipients from November 2011 to October 2013, and correlated with outcome measures.ResultsOverall, 57 SPK transplant recipients were analysed. The mean age was 42.0 years (standard deviation [SD]: 7.60 years), 27 (52%) were male and the mean body mass index was 25.43kg/m² (SD: 3.11kg/m²). The mean pancreas and kidney cold ischaemic times were 703 minutes (SD: 182 minutes) and 850 minutes (SD: 192 minutes) respectively. The median total LOS and mean CCU LOS was 17 days (range: 8–79 days) and 7 days (SD: 4.04 days) respectively. When correlated with risk prediction scores, Waterlow score was the only significant predictor of total LOS and CCU LOS (p<0.001 [Spearman’s correlation] and p=0.001 [Pearson’s correlation] respectively).ConclusionsPreoperative risk prediction plays an important part in planning perioperative care. To date, no validated risk prediction scoring system exists for SPK transplantation. This prospective study indicates that Waterlow score identifies high risk individuals and has value in the prediction of outcome following SPK transplantation.     

Experience of managing open fractures of the lower limb at a major trauma centre

Introduction

In April 2012 the John Radcliffe Hospital in Oxford became a major trauma centre (MTC). The British Orthopaedic Association and British Association of Plastic, Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4) require system-wide changes in referral practice that may be facilitated by the MTC and its associated major trauma network.

Methods

From 2008 to 2013 a multistep audit of compliance with BOAST 4 was conducted to assess referral patterns, timing of surgery and outcomes (surgical site infection rates), to determine changes following local intervention and the establishment of the MTC.

Results

Over the study period, 50 patients had soft tissue cover for an open lower limb fracture and there was a significant increase in the proportion of patients receiving definitive fixation in our centre (p=0.036). The median time from injury to soft tissue cover fell from 6.0 days to 3.5 days (p=0.051) and the median time from definitive fixation to soft tissue cover fell from 5.0 days to 2.0 days (p=0.003). The deep infection rate fell from 27% to 8% (p=0.247). However, in 2013 many patients still experienced a delay of >72 hours between injury and soft tissue cover, primarily owing to a lack of capacity for providing soft tissue cover.

Conclusions

Our experience may be relevant to other MTCs seeking to identify barriers to optimising the management of patients with these injuries.     

Phosphorylation of Izumo1 and its role in male infertility

Izumo1 is a testis-specific gene product, whose function is essential for sperm-egg fusion. Throughout its lifespan, Izumo1 is posttranslationally modified, being both N-linked glycosylated on its extracellular domain and phosphorylated on the intracellular C-terminal tail. Within the caput regions of the rat epididymis, two phosphorylation events have been documented. However, as sperm pass through the epididymis, this cytoplasmic portion of Izumo1 has been shown to contain up to seven phosphorylation sites. Remarkably, in the rat, in correlation with these events, Izumo1 undergoes sub-cellular re-location, moving from the head/tail regions of the spermatozoa, to a predominantly equatorial segment location once they have reached the caudal end of the epididymis.