Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Aims Experimental data point towards a favourable effect of low serum concentrations of complement mannose-binding lectin (MBL) on myocardial ischaemia/reperfusion (I/R) injury. As comparable data on the role of MBL in human I/R injury is lacking, we investigated the influence of low serum MBL concentrations on mortality of patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods and results Mannose-binding lectin was determined in 890 acute STEMI patients that were prospectively recruited in the APEX-AMI trial. This trial had a primary endpoint of death through Day 30 and secondary endpoints of death through Day 90 and the composite of death, cardiogenic shock, or congestive heart failure (CHF) through Days 30 and 90. Samples were taken immediately before PCI and the analysis of MBL limited to patients having received placebo. Patients with serum MBL levels of or below 100 ng/mL were considered to be functionally deficient. Of the 890 patients, 127 had functional MBL deficiency (14.3%). Characteristics of patients with MBL deficiency and those with MBL levels >100 ng/mL did not differ. In patients with MBL deficiency, there was 1 death (0.79%) compared with 42 deaths (5.51%) in patients with MBL levels >100 ng/mL (P = 0.0233) representing an absolute and relative lower mortality in MBL deficient patients of 4.7 and 85%, respectively. Functional MBL deficiency, however, was not associated with decreased risk of the combined endpoints of death and shock or death, shock, and CHF, respectively. Conclusion Functional deficiency of complement MBL is associated with reduced mortality in patients with STEMI undergoing PCI. This unique finding suggests that a component of the innate immune system affects mortality in STEMI patients undergoing primary PCI. Trial Registration: clinicaltrials.gov, Identifier: NCT0009163

Effects of Selective Matrix Metalloproteinase Inhibitor (PG-116800) to Prevent Ventricular Remodeling After Myocardial Infarction Results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) Trial

ObjectivesWe sought to determine whether matrix metalloproteinase (MMP) inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial infarction (MI).BackgroundPG-116800 is an oral MMP inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure.MethodsIn an international, randomized, double-blind, placebo-controlled study, 253 patients with first ST-segment elevation MI and ejection fraction between 15% and 40% were enrolled 48± 24 h after MI and treated with placebo or PG-116800 for 90 days. Major efficacy end points were changes in LV volumes as determined by serial echocardiography, and clinical and safety outcomes were also collected.ResultsIn total, 203 patients (80%) completed 90 days of treatment and had evaluable baseline and 90-day echocardiograms. The proportion of patients with anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs. 91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ between PG-116800-treated and placebo-treated patients. There was no difference in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800 versus placebo (5.09 ± 1.45 ml/m2vs. 5.48 ± 1.41 ml/m2, p = 0.42). Changes in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity index, plus rates of death or reinfarction were not significantly improved with PG-116800. PG-116800 was well tolerated; however, there was increased incidence of arthralgia and joint stiffness without significant increase in overall musculoskeletal adverse events (21% vs. 15%, p = 0.33).ConclusionsMatrix metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or improve clinical outcomes after MI

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Border crossings in the African travel narratives of Ibn Battuta, Richard Burton and Paul Theroux

This article compares the representation of African borders in the 14th-century travelogue of Ibn Battuta, the 19th-century travel narrative of Richard Burton and the 21st-century travel writing of Paul Theroux. It examines the mutually constitutive relationship between conceptions of literal territorial boundaries and the figurative boundaries of the subject that ventures across borders in Africa. The border is seen as a liminal zone which paradoxically separates and joins spaces. Accounts of border crossings in travel writing from different periods suggest the historicity and cultural specificity of conceptions of geographical borders, and the way they index the “boundaries” of the subjects who cross them. Tracing the transformations in these conceptions of literal and metaphorical borders allows one to chart the emergence of the dominant contemporary idea of “Africa” as the inscrutable, savage continent

Characterizing benthic macroinvertebrate and algal biological condition gradient models for California wadeable Streams, USA

The Biological Condition Gradient (BCG) is a conceptual model that describes changes in aquatic communities under increasing levels of anthropogenic stress. The BCG helps decision-makers connect narrative water quality goals (e.g., maintenance of natural structure and function) to quantitative measures of ecological condition by linking index thresholds based on statistical distributions (e.g., percentiles of reference distributions) to expert descriptions of changes in biological condition along disturbance gradients. As a result, the BCG may be more meaningful to managers and the public than indices alone. To develop a BCG model, biological response to stress is divided into 6 levels of condition, represented as changes in biological structure (abundance and diversity of pollution sensitive versus tolerant taxa) and function. We developed benthic macroinvertebrate (BMI) and algal BCG models for California perennial wadeable streams to support interpretation of percentiles of reference-based thresholds for bioassessment indices (i.e., the California Stream Condition Index [CSCI] for BMI and the Algal Stream Condition Index [ASCI] for diatoms and soft-bodied algae). Two panels (one of BMI ecologists and the other of algal ecologists) each calibrated a general BCG model to California wadeable streams by first assigning taxa to specific tolerance and sensitivity attributes, and then independently assigning test samples (264 BMI and 248 algae samples) to BCG Levels 1–6. Consensus on the assignments was developed within each assemblage panel using a modified Delphi method. Panels then developed detailed narratives of changes in BMI and algal taxa that correspond to the 6 BCG levels. Consensus among experts was high, with 81% and 82% expert agreement within 0.5 units of assigned BCG level for BMIs and algae, respectively. According to both BCG models, the 10th percentiles index scores at reference sites corresponded to a BCG Level 3, suggesting that this type of threshold would protect against moderate changes in structure and function while allowing loss of some sensitive taxa. The BCG provides a framework to interpret changes in aquatic biological condition along a gradient of stress. The resulting relationship between index scores and BCG levels and narratives can help decision-makers select thresholds and communicate how these values protect aquatic life use goals

Anaesthesia and airway management in mucopolysaccharidosis

Abstract This paper provides a detailed overview and dis-cussion of anaesthesia in patients with mucopolysacchari-dosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical mani-festations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardio-vascular manifestations poses a high anaesthetic risk to these patients. Typical anaesthetic problems include airway obstruction after induction or extubation, intubation diffi-culties or failure [can’t intubate, can’t ventilate (CICV)], possible emergency tracheostomy and cardiovascular and cervical spine issues. Because of the high anaesthetic risk, the benefits of a procedure in patients with MPS shoul

Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y(12) Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial

Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.Peer reviewe

Knowing and teaching the indigenous other : teachers’ engagement with Aboriginal and Torres Strait Islander cultures

This is the first empirical study of teacher knowledge and classroom practice in Aboriginal and Torres Strait Islander education. It describes the construction of a survey instrument to measure non-Indigenous Australian teachers’ knowledge of Indigenous culture and place, frequency of everyday intercultural exchanges, and attempts to integrate Indigenous knowledge into classroom practice. Many teachers reported low levels of knowledge of Indigenous cultures, and limited encounters outside of school. While the cohort expressed dissatisfaction with pre-service training, exposure to pre- and in-service courses in Indigenous education correlated with higher levels of cultural knowledge and cultural engagement. Teachers with higher levels of cultural engagement were more likely to attempt to integrate Indigenous knowledges in curriculum and pedagogy