Isolation of a novel intertypic recombinant human mastadenovirus B2 from two unrelated bone marrow transplant recipients.

Human adenoviruses (HAdV) are well-known opportunistic pathogens of immunocompromised adult and pediatric patients but specific associations between HAdV species or individual HAdV types and disease are poorly understood. In this study we report the isolation of a novel HAdV-B2 genotype from two unrelated immunocompromised patients, both recipients of a hematopoietic cell transplant. In both patients, the course of HAdV infection is consistent with a scenario of reactivation of a latent virus rather than a primary opportunistic infection. Archived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular characterization. Virus isolates were recovered from patient 1 from PCR-positive urine specimens obtained at days 103 and 116 after transplant in association with gross hematuria, and from a stool specimen obtained 138 days after transplant in association with diarrhea. An isolate was recovered from patient 2 from a PCR-positive urine specimen. Hexon and fiber gene amplification and sequencing were carried out for initial molecular typing, identifying the isolates as an intertypic recombinant with a HAdV-11-like hexon gene and a HAdV-77-like fiber gene. Comprehensive restriction fragment length polymorphism (RFLP) analysis was performed on viral DNA purified from urine and stool isolates, and next generation whole genome sequencing was carried out on purified viral genomic DNA. The genomes of the two isolated strains are 99.5% identical and represent the same RFLP genomic variant. The identified virus is a novel HAdV-B2 genotype designated HAdV-78 exhibiting a HAdV-11-like penton base, a HAdV-11-like hexon and a HAdV-77-like fiber (P11H11F77).

Invasive candidiasis in liver transplant patients: Incidence and risk factors in a pediatric cohort.

Prolonged OR, re-transplantation, and high-volume intraoperative transfusion have been associated with increased risk for IC in adult LT recipients. Antifungal prophylaxis is recommended for adult patients with these risk factors. There are limited data on the incidence of and risk factors for IC in pediatric LT recipients. A retrospective cohort study of all pediatric LT patients at the CHOP between 2000 and 2012 and the CHP between 2004 and 2012 was performed to define the incidence of IC within 30 days of LT. A 3:1 matched case-control study with incidence density sampling was performed. Conditional logistic regression analyses were used to explore risk factors associated with IC. Among 397 recipients, the incidence of IC was 2.5%. Bivariate analyses showed that ICU admission prior to transplant, OR > 10 h, intraoperative volume infusion of >300 mL/kg, and broad-spectrum antibiotics were significantly associated with IC. In a multivariate model, only ICU admission remained significantly associated with IC. Antifungal prophylaxis was not significantly protective against IC. The low incidence of IC and lack of an identified protective effect from antifungal prophylaxis suggest that prophylaxis in pediatric LT recipients should not be routinely recommended to prevent IC events in the first 30 days post-transplant.

A Case of Adenovirus Viremia in a Pediatric Liver Transplant Recipient With Neutropenia and Lymphopenia: Who and When Should We Treat?

Human adenovirus (HAdV) is one of the most feared infections among immunocompromised patients. In particular, in liver transplant patients, HAdV has been implicated in acute liver failure with resultant mortality. The development of current molecular techniques and surveillance testing protocols have provided tools for early detection of HAdV infection, prior to or at the early onset of HAdV disease. Although reduction in immune suppression is the mainstay of therapy, many researchers have also advocated for early administration of antiviral therapy. In multiple reports, cidofovir treatment has been associated with declines in HAdV viral loads or clinical improvement in solid organ and bone marrow transplant recipients. However, there have also been case reports that raise questions about the effectiveness of antiviral therapy in controlling systemic HAdV disease. We report a case of a 26-month-old male recipient of a liver transplantation for hepatoblastoma who developed adenoviremia with an associated hepatitis and gastroenteritis. He recovered with reduced immune suppression but without antiviral therapy, thus avoiding potential toxicities associated with cidofovir therapy. This case a contrast to previous reports, and it highlights the ambiguity regarding which patients should receive HAdV-specific antiviral therapy. Additional knowledge regarding specific pediatric host factors and HAdV factors that predict poor outcomes are needed. Such information would allow clinicians to better stratify patients by risk at the time of adenoviremia detection so that low-risk patients are not unnecessarily exposed to medications with potential toxicities.

Merging of the National Cancer Institute-funded cooperative oncology group data with an administrative data source to develop a more effective platform for clinical trial analysis and comparative effectiveness research: a report from the Children's Oncology Group.

PURPOSE: The National Cancer Institute-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions. METHODS: COG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data. RESULTS: Of 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described. CONCLUSIONS: These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy.

Invasive fungal infections in the paediatric and neonatal population: diagnostics and management issues.

Invasive fungal infections in children appear to have increased over the past few decades. Especially neonates and children with primary and secondary immunodeficiencies are at risk. Candida and Aspergillus spp. are the most commonly isolated organisms. In addition, Malassezia may cause systemic infections in newborns and zygomycosis is important because of its rising incidence and high case fatality rate. Timely diagnosis and initiation of appropriate antifungal therapy is imperative for improving outcomes. However, traditional techniques are time-consuming and representative sample material, using invasive procedures, may be difficult to obtain in the paediatric setting. This review provides an overview of the advances in detection and rapid species identification, with a focus on issues relevant in these settings. Subsequently, the current antifungal treatment options for neonates and children are discussed in light of the antifungal spectrum of the available agents and the specific pharmacokinetic properties in different age groups. Although a multitude of newer antifungal compounds have become available within the last decade, further studies are necessary to clearly establish the role for each of these agents among neonates and children.

Determination of excimer laser ablation rates of corneal tissue using wax impressions of ablation craters and white-light interferometry.

BACKGROUND AND OBJECTIVE: Efforts to better understand the processes of corneal ablation are aided by a means to precisely measure corneal tissue ablation rates. MATERIALS AND METHODS: A white-light interferometer was used to measure the depth of argon fluoride laser ablation craters and wax impressions of the ablation craters. The technique was validated using polymethylmethacrylate (PMMA), and was then used to measure the ablation rate of bovine corneal tissue. RESULTS: The ablation rate was measured as 0.47 microm/pulse from direct measurement of the PMMA ablation craters and as 0.48 microm/pulse from measurement of the corresponding wax impressions. The ablation rate of bovine corneal tissue was found to be 0.90 microm/pulse. CONCLUSIONS: Wax impressions provide a valid representation of ablation craters. The ablation depth of corneal tissue and PMMA was found to increase linearly with increasing number of laser pulses, and the slope of the regression lines provided a measure of the laser ablation rate.

Resuscitation of pulmonary contusion: hypertonic saline is not beneficial.

We postulated that hypertonic solutions could minimize the accumulation of lung water and subsequent respiratory derangements that occur after pulmonary contusion. Anesthetized pigs underwent contusion of the right chest at baseline and then were hemorrhaged (30 cc/kg) over 20 min. They were resuscitated with either 7.5% NaCl (4 cc/kg) or .9% saline (90 cc/kg) for 20 min and observed for 4 h. Gravimetric lung weights and spiral computed tomography scans were used to quantitate lung water. The hemodynamic response to contusion and hemorrhage was similar in both resuscitation groups. Arterial oxygen tension was not significantly altered by the method of resuscitation and remained close to baseline values for the entirety of the experiment. Static compliance measurements were significantly decreased from baseline in both groups following pulmonary contusion. There were no differences in wet to dry lung weights or computed tomography scan injury volume between groups. We conclude that small volume hypertonic saline resuscitation does not reduce the magnitude of lung injury or provide substantial physiologic benefit over isotonic solutions following pulmonary contusion.

Resuscitation of pulmonary contusion: effects of a red cell substitute.

OBJECTIVE: To determine the impact of a vasoactive red cell substitute, diaspirin cross-linked hemoglobin, on respiratory derangements after traumatic lung injury. DESIGN: Randomized, controlled animal experiment. SETTING: Large-animal laboratory. SUBJECTS: Mechanically ventilated, anesthetized young Yorkshire male swine (15 to 20 kg). INTERVENTIONS: Pigs (n = 6/group) received two pneumatic blasts to the right thoracic cage at baseline, were hemorrhaged 30 mL/kg from t = 0 to 20 mins, resuscitated with 0.9% saline (group 1, 90 mL/ kg) or diaspirin cross-linked hemoglobin (group 2, 15 mL/kg) from t = 20 to 40 mins, and then observed to t = 240 mins. MEASUREMENTS AND MAIN RESULTS: Serial pulmonary and systemic hemodynamic measurements, total thoracic compliance assessment, spiral three-dimensional computed tomography scan, and lung weights (n = 3/group) were used to assess lesion size and lung water. Mean arterial pressure was restored in both animal groups. Mean pulmonary arterial pressure was significantly higher after resuscitation in animals receiving the red cell substitute. Oxygenation worsened mildly in both groups. Compliance diminished in both groups but was significantly worse at the end of the experiment in animals infused with diaspirin cross-linked hemoglobin. Right lung weights and right thoracic computed tomography scan volume were higher with diaspirin cross-linked hemoglobin than with saline. CONCLUSIONS: After pulmonary contusion, resuscitation with diaspirin cross-linked hemoglobin led to pulmonary hypertension, greater pulmonary contusion lesion size, and stiffer lungs in this porcine model.

Do surgeons have a role as infectious disease consultants?

BACKGROUND: Antibiotic drug restriction policies have become widespread in North America hospitals mandating medical infectious disease consultation for use of routine antimicrobial agents. OBJECTIVE: To determine physician and institutional attitudes regarding the credibility of surgeons in the area of infectious disease. DESIGN: A survey of the Surgical Infectious Disease Society (SIS) membership. PARTICIPANTS: Members of the SIS practicing in the United States and Canada (n = 464) were sent a simple opinion poll regarding surgical infectious disease specialists. After receiving the survey, the SIS members were given approximately 4 weeks to anonymously complete the questionnaire and return it to our office. RESULTS: Responses were received from 198 SIS members (43%). Most were from large (> 400 bed) institutions (63%), and the majority of them were from university centers (76%). Predictably, 86% of the respondents were in full-time academic practice. Some SIS respondents (21%) had undergone special training in infectious disease, and of these, 63% actually had completed a formal surgical infectious disease fellowship. Antibiotic restriction policies were nearly universal and required in 87% of institutions. Only 44% of surgeons in these hospitals, however, were privileged to release antibiotic drugs. Medical infectious disease physicians recognized surgical expertise in infectious disease in few instances (32%). The great majority of responding SIS members (81%) believed that an examination or certification in infectious disease for surgeons was not warranted. CONCLUSIONS: Antibiotic drug restriction is prevalent in North America, and medical infectious disease specialists do not generally recognize surgical expertise in the area of infectious disease. Despite this environment, responding SIS members believe that special credentialing of surgeons in the area of infectious disease is unnecessary.