Foxp3+ T cells induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes.

Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.

Outreach and Early Warning Systems (EWS) for the prevention of intensive care admission and death of critically ill adult patients on general hospital wards

BACKGROUND: Despite the fact that outreach and early warning systems (EWS) are an integral part of a hospital wide systems approach to improve the early identification and management of deteriorating patients on general hospital wards, the widespread implementation of these interventions in practice is not based on robust research evidence. OBJECTIVES: The primary objective was to determine the impact of critical care outreach services on hospital mortality rates. Secondary objectives included determining the effect of outreach services on intensive care unit (ICU) admission patterns, length of hospital stay and adverse events. SEARCH STRATEGY: The review authors searched the following electronic databases: EPOC Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) and other Cochrane databases (all on The Cochrane Library 2006, Issue 3), MEDLINE (1996-June week 3 2006), EMBASE (1974-week 26 2006), CINAHL (1982-July week 5 2006), First Search (1992-2005) and CAB Health (1990-July 2006); also reference lists of relevant articles, conference abstracts, and made contact with experts and critical care organisations for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials (CCTs), controlled before and after studies (CBAs) and interrupted time series designs (ITS) which measured hospital mortality, unanticipated ICU admissions, ICU readmissions, length of hospital stay and adverse events following implementation of outreach and EWS in a general hospital ward to identify deteriorating adult patients versus general hospital ward setting without outreach and EWS were included in the review. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and two review authors assessed the methodological quality of the included studies. Meta-analysis was not possible due to heterogeneity. Summary statistics and descriptive summaries of primary and secondary outcomes are presented for each study. MAIN RESULTS: Two cluster-randomised control trials were included: one randomised at hospital level (23 hospitals in Australia) and one at ward level (16 wards in the UK). The primary outcome in the Australian trial (a composite score comprising incidence of unexpected cardiac arrests, unexpected deaths and unplanned ICU admissions) showed no statistical significant difference between control and medical emergency team (MET) hospitals (adjusted P value 0.640; adjusted odds ratio (OR) 0.98; 95% confidence interval (CI) 0.83 to 1.16). The UK-based trial found that outreach reduced in-hospital mortality (adjusted OR 0.52; 95% CI 0.32 to 0.85) compared with the control group. AUTHORS' CONCLUSIONS: The evidence from this review highlights the diversity and poor methodological quality of most studies investigating outreach. The results of the two included studies showed either no evidence of the effectiveness of outreach or a reduction in overall mortality in patients receiving outreach. The lack of evidence on outreach requires further multi-site RCT's to determine potential effectiveness.

Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death. Published on behalf of the European Society of Cardiology. © The Author 2010.

Children’s Burial Grounds in Ireland (Cilliní) and Parental Emotions Toward Infant Death

Cilliní—or children’s burial grounds—were the designated resting places for unbaptized infants and other members of Irish society who were considered unsuitable by the Roman Catholic Church for burial in consecrated ground. The sites appear to have proliferated from the seventeenth century onwards in the wake of the Counter-Reformation. While a number of previous studies have attempted to relate their apparently marginal characteristics to the liminality of Limbo, evidence drawn from the archaeological record and oral history accounts suggests that it was only the Roman Catholic Church that considered cilliní, and those interred within, to be marginal. In contrast, the evidence suggests that the families of the dead regarded the cemeteries as important places of burial and treated them in a similar manner to consecrated burial grounds.

Acute complications and drug misuse are important causes of death for children and young adults with type 1 diabetes - Results from the Yorkshire Register of Diabetes in Children and Young Adults

OBJECTOVE - To examine mortality rates and causes of death among subjects diagnosed with type I diabetes aged

Quantifying Alcohol-Related Mortality: Should Alcohol-Related Contributory Causes of Death be Included?

Aims: The aim of the study was to assess whether alcohol-related mortality data in the UK should be extended to include contributory as well as underlying cause of death. Methods: A total of 101,320 deaths registered in Northern Ireland between 2001 and 2007 were analysed to determine the quantity and characteristics of those with an underlying or contributory alcohol-related cause of death. Results: Alcohol was found to be an underlying cause of death in 1690 cases (1.7% of deaths) and a contributory cause in a further 1105 cases. Analyses show that the addition of alcohol-related contributory causes of deaths would increase the male-female ratio, result in steeper socio-economic gradients and amplify the apparent rate of increase of alcohol-related deaths. The significant contribution of alcohol to external causes of death, such as accidents and suicide, is also more evident. Conclusions: Using only underlying cause of death undoubtedly underestimates the burden of alcohol-related harm and may provide an inaccurate picture of those most likely to suffer from an alcohol-related death, especially among younger men.