Intestinal transplantation under tacrolimus monotherapy after perioperative lymphoid depletion with rabbit anti-thymocyte globulin (thymoglobulin®)

Modifications in the timing and dosage of immunosuppression can ameliorate the morbidity and mortality that has prevented widespread use of intestinal transplantation (ITx) in children. Thirty-six patients receiving ITx, aged 5 months to 20 years were given 2-3 mg(kg of rabbit anti-thymocyte globulin (rATG, thymoglobulin®) just before ITx, and 2-3 mg(kg post-operatively (total 5 mg(kg). Twice daily doses of tacrolimus (TAC) were begun enterally within 24 h after graft reperfusion with reduction of dose quantity or frequency after 3 months. Prednisone or other agents were given to treat breakthrough rejection. After 8-28 months follow-up (mean 15.8 ± 5.3), 1- and 2-year patient and graft survival is 100% and 94%, respectively. Despite a 44% incidence of acute rejection in the first month, 16 of the 34 (47%) survivors are on TAC (n = 14) or sirolimus (n = 2) monotherapy; 15 receive TAC plus low dose prednisone; one each receive TAC plus sirolimus, TAC plus azathioprine and TAC plus sirolimus and prednisone. There was a low incidence of immunosuppression-related complications. This strategy of immunosuppression minimized maintenance TAC exposure, facilitated the long-term control of rejection, decreased the incidence of opportunistic infections, and resulted in a high rate of patient and graft survival. Copyright © Blackwell Munksgaard 2005

Adherence to secondary prophylaxis and disease recurrence in 536 Brazilian children with rheumatic fever

<p>Abstract</p> <p>Background</p> <p>More than 15 million people worldwide have rheumatic fever (RF) and rheumatic heart disease due to RF. Secondary prophylaxis is a critical cost-effective intervention for preventing morbidity and mortality related to RF. Ensuring adequate adherence to secondary prophylaxis for RF is a challenging task. This study aimed to describe the rates of recurrent episodes of RF, quantify adherence to secondary prophylaxis, and examine the effects of medication adherence to the rates of RF in a cohort of Brazilian children and adolescents with RF.</p> <p>Methods</p> <p>This retrospective study took place in the Pediatric Rheumatology outpatient clinic at a tertiary care hospital (Instituto de Puericultura e Pediatria Martagão Gesteira) in Rio de Janeiro, Brazil, and included patients with a diagnosis of RF from 1985 to 2005.</p> <p>Results</p> <p>536 patients with RF comprised the study sample. Recurrent episodes of RF occurred in 88 of 536 patients (16.5%). Patients with a recurrent episode of RF were younger (p < 0.0001), more frequently males (p = 0.003), and less adherent (p < 0.0001) to secondary prophylaxis than patients without RF recurrence. Non-adherence to medication at any time during follow-up was detected in 35% of patients. Rates of non-adherence were higher in the group of patients that were lost to follow-up (42%) than in the group of patients still in follow-up (32%) (p = 0.027). Appointment frequency was inadequate in 10% of patients. Higher rates of inadequate appointment frequency were observed among patients who were eventually lost to follow-up (14.5%) than in patients who were successfully followed-up (8%) (p = 0.022). 180 patients (33.5%) were lost to follow up at some point in time.</p> <p>Conclusions</p> <p>We recommend implementation of a registry, and a system of active search of missing patients in every service responsible for the follow-up of RF patients. Measures to increase adherence to secondary prophylaxis need to be implemented formally, once non-adherence to secondary prophylaxis is the main cause of RF recurrence. Detection of irregularity in secondary prophylaxis or in appointments should be an alert about the possibility of loss of follow-up and closer observation should be instituted.</p

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/