Daclizumab therapy for children with corticosteroid-resistant acute graft-vs.-host disease

Abstract:  MAbs such as daclizumab have shown promising results in the treatment of corticosteroid-resistant aGVHD. Data describing the efficacy of MAbs in children are limited. We describe the efficacy of daclizumab in children with corticosteroid-resistant aGVHD. Seventeen children (0.4–16.2 yr) received daclizumab for aGVHD. Safety was evaluated in all 17. Response was evaluated in the 15 children who received a full course of daclizumab. A PR was defined as improvement of aGVHD symptoms in at least one organ without worsening in other organs. We observed an overall response rate (CR plus PR) of 40% (6/15). Four children had a CR and two had a PR. aGVHD involving the gut had the highest response rate (five of 10; 50%). Adverse effects attributed to daclizumab were limited to an episode of reactive arthritis. Mortality was high (47%; eight of 17) though five of the six responders to daclizumab survived. The mean length of follow-up in the surviving nine patients was 32 months (range seven to 48). We conclude that daclizumab is effective in the treatment of children with corticosteroid-resistant aGVHD, especially in patients with gut involvement.     

Circulating leptin levels after cardiopulmonary bypass in children

OBJECTIVE: To characterize the dynamics of circulating leptin in children after cardiac surgery with cardiopulmonary bypass (CPB), which is known to induce a systemic inflammatory response. DESIGN: Investigative study. SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: Eight children (age range, 3 months to 13 years) undergoing CPB to correct congenital heart disease. INTERVENTIONS: The time courses of leptin and cortisol levels were determined. Serial blood samples were collected from the arterial catheter or from the CPB circuit preoperatively; on termination of CPB; and at 2, 4, 8, 12, 18, and 24 hours postoperatively. Plasma was recovered immediately, divided into aliquots, and frozen at -70 degrees C until use. Leptin was measured by a human leptin radioimmunoassay kit. MEASUREMENTS AND MAIN RESULTS: Leptin levels during CPB decreased to 50% of pre-CPB levels (p < 0.01). After termination of CPB, levels increased gradually and peaked at 12 hours postoperatively (10 P.M. to 1 A.M.). Cortisol levels were inversely correlated to leptin levels (p = 0.016). CONCLUSION: CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, showing an inverse relationship between leptin and cortisol, suggesting a relationship between the neurobiology of these systems that could be important for the neuroendocrine response to CPB. A prognostic role of leptin and its relationship to cortisol after CPB warrant further study.     

An intradermal skin test for determination of immunity to varicella

AIMS—To evaluate the usefulness of a diluted, inactivated solution of attenuated varicella vaccine in predicting susceptibility to varicella and its correlation with specific antibody titre to varicella.METHODS—In a prospective blinded study, 63 healthy subjects (aged 2-43 years) were studied. Skin test solution was prepared from vials of OKA strain virus which was inactivated by exposure of the vials to room temperature for 10 days; solution was diluted at 1/50 with normal saline and kept at 4°C until used for skin testing. The material was injected intradermally. Serum samples were drawn prior to skin testing and kept at ?70°C until analysis for antibody assay by the indirect fluorescent antibody (IFA) method.RESULTS—Forty three patients were IFA antibody positive; 41 of them reacted to the skin test. One of the 20 IFA negative patients reacted to the skin test. Sixteen patients had two serological tests performed, one month apart. Four out of these 16 patients tested negative with the skin test. All four had negative serology on both samples. Six of the 12 IFA positive patients showed a boost in the antibody titre one month after application of the skin test. The specificity and sensitivity of the skin test compared to the IFA assay were both 95%, and the positive and negative predictive values were 97% and 90% respectively.CONCLUSIONS—Results suggest that a varicella skin test prepared using this simple and relatively cheap method is a safe, sensitive, and specific tool by which to assess immunity to varicella.     

Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections

The aim of this study was to evaluate the impact of carbapenem-resistant K. pneumoniae bloodstream infections on mortality. During the study period 42, 68 and 120 patients were identified with carbapenem-resistant, extended-spectrum b-lactamase producers (ESBL) and susceptible K. pneumoniae bloodstream infections, respectively. Patients with carbapenem-resistant K. pneumoniae had higher rates of prior antimicrobial exposure, other nosocomial infections, and use of invasive devices. Infection-related mortality was 48% for carbapenem-resistant, 22% for ESBL producers and 17% for susceptible K. pneumoniae. Independent risk factors for infection-related mortality were Pitt bacteraemia score, Charlson score and carbapenem resistance.     

BK virus-associated hemorrhagic cystitis presenting as mural nodules in the urinary bladder after hematopoietic stem cell transplantation

We report an unusual sonographic presentation of late-onset hemorrhagic cystitis caused by BK virus infection in an 8-year-old who had undergone hematopoietic stem cell transplantation for treatment of relapsed acute lymphoblastic leukemia. Sonography showed the presence of multiple bladder nodules in a background of diffuse bladder wall thickening. The dominant bladder nodule showed increase in size on serial sonograms and was vascularized on Doppler interrogation. Biopsy confirmed BK virus-associated cystitis. Recognition of this sonographic appearance in the appropriate clinical setting might obviate the need for biopsy in these children.     

Rehabilitation of Children With Traumatic Brain Injury: A Critical Review

The purpose of this critical review of the English literature published between 1975 and 2009 was to assess the quality of the evidence for the efficacy of rehabilitation intervention after traumatic brain injury in children. “Evidence for intervention studies” was used to classify the research strength of design and report. Only a minority (16/439) of the published studies has been related to traumatic brain injury in children and has used a scientific or quasiscientific design. Only one study met the criteria of class I “evidence for intervention” studies. However, this study included adults, as well as children. The other 15 studies, although reporting positive results, had many methodologic deficiencies, and consequently their validity is questionable. Although the methodologic and ethical difficulties involved are acknowleged, a multicenter approach is required to achieve valid conclusions. Use of designs such as comparative effectiveness research might prove to be a practical solution. High-quality intervention research would facilitate stronger evidence-based counseling for children and families requiring posttraumatic brain injury intervention and to policy makers.     

Optimal echo times for multi‐gradient echo‐based B0 field‐mapping

B₀ field maps are used ubiquitously in neuroimaging, in disciplines ranging from magnetic resonance spectroscopy to temperature mapping and susceptibility‐weighted imaging. Most B₀ maps are acquired using standard gradient‐echo–based vendor‐provided sequences, often comprised of two echoes spaced a few milliseconds apart. Herein, we analyze the optimal spacing of echo times, defined as those maximizing precision—minimizing the standard deviation—for a fixed total acquisition time. Field estimation is carried out using a weighted least squares estimator. The standard deviation is shown to be approximately inversely proportional to the total acquisition time, suggesting a law of diminishing returns, whereby substantial gains are obtained up to a certain point, with little improvement beyond that point. Validations are provided in a phantom and a group of volunteers. Multi‐gradient echo sequences are readily available on all manufacturer platforms, making our recommendations straightforward to implement on any modern scanner.