Definition of constitutive and stage-enriched promoters in the rodent malaria parasite, Plasmodium yoelii.

BACKGROUND: Well-defined promoters are essential elements for genetic studies in all organisms, and enable controlled expression of endogenous genes, transgene expression, and gene editing. Despite this, there is a paucity of defined promoters for the rodent-infectious malaria parasites. This is especially true for Plasmodium yoelii, which is often used to study the mosquito and liver stages of malarial infection, as well as host immune responses to infection. METHODS: Here six promoters were selected from across the parasite's life cycle (clag-a, dynein heavy chain delta, lap4, trap, uis4, lisp2) that have been invoked in the literature as controlling their genes in a stage-specific manner. A minimal promoter length for the constitutive pybip promoter that confers strong expression levels was also determined, which is useful for expression of reporters and gene editing enzymes. RESULTS: Instead, it was observed that these promoters confer stage-enriched gene control, as some parasites also effectively use these promoters in other stages. Thus, when used alone, these promoters could complicate the interpretation of results obtained from promoter swaps, stage-targeted recombination, or gene editing experiments. CONCLUSIONS: Together these data indicate that achieving stage-specific effects, such as gene editing, is likely best done using a two-component system with independent promoter activities overlapping only in the intended life cycle stage.

Transitions Pop-ups: Co-designing client-centred support for disabled youth transitioning to adult life.

Background: When transitioning to adulthood, youth with disabilities and their families face many service gaps. Successful inter-agency collaborations can promote family-centred, inclusive transition support amenable to personal choice and health conditions. This paper reports the 3-year co-design process of an innovative transition service that links a pediatric hospital and adult service agencies and addresses key areas of transition preparedness with joint accountability. Methods: A team of pediatric rehabilitation professionals, adult service providers, young adults with disabilities and their families, and researchers engaged in a co-design process over three years. Following a design thinking (DT) framework, the team went through an iterative process of Empathize. Define, Ideation, Prototyping, and Testing phases. The trial-and-error process allowed for deeper reflection and an opportunity to pivot the design. Results: The co-design yielded Transitions Pop-ups, a nimble service model that can "pop up" at critical times and places to meet clients' urgent and emergent transition-related needs. Two pilot sessions were conducted at the testing phase with adult service agencies. The final model included five key elements: (1) community partnership; (2) targeted information sharing; (3) peer mentoring; (4) action (on-the-spot completion of a key transition task/activity such as submitting an adult funding application); and (5) warm handover. Conclusion: The co-design process highlighted the importance of open communication and iterative prototype testing as a means for trialing new ideas and clarifying the intent of the project. The DT framework optimally facilitated the co-development of a contextually relevant and sustainable service model for pediatric rehabilitation clients and families.

Funding employment inclusion for Ontario youth with disabilities: a theoretical cost-benefit model.

Early engagement in employment-related activities is associated with greater lifetime labor force attachment, which correlates with positive health, social, and quality of life outcomes. People with disabilities often require vocational intervention to enter and remain in the workforce and reap the employment-related health and social benefits. Their labor force attachment brings about the added societal-level benefits of increased tax contributions and reduced social assistance funding. Reason and evidence both support the need for early intervention to facilitate young people with disabilities' workforce entry. Based on available evidence and best practices, and in conjunction with expert input, a cost-benefit model was constructed to provide support for public investment in early employment intervention by demonstrating the societal-level benefits that could be projected. Results indicate the potential benefits for investment in early, targeted employment intervention at a societal level. Two personas were crafted to demonstrate the lifetime societal-level impact of investment in intervention for an individual with disabilities. The results provide relevant arguments for advocates, policy makers, program directors, and people entering adulthood with disabilities to understand the benefits of investing in interventions with the goal of long-term public savings.

Facilitating virtual social connections for youth with disabilities: lessons for post-COVID-19 programming.

PURPOSE: Social connections are essential for the development of life skills for youth. Youth with disabilities have long faced barriers to meaningful social connections. The onset of COVID-19 increased barriers to social connections for all youth, and also led to enhanced use of virtual platforms in paediatric rehabilitation programming. Harnessing this opportunity, service providers created a suite of online programs to foster social connections and friendships. The current study explores participant and service provider experiences of such programs. METHODS: This qualitative descriptive study used interviews and focus groups to explore how youth with disabilities (n = 8), their parents (n = 7), and service providers (n = 13) involved in program development and delivery experienced the programs, the accessibility of the virtual platforms, and their social connections in relation to program participation. RESULTS: Participants were satisfied with the programs' content, accessibility and ability to meet their social needs. Qualitative themes included facilitating social connections, accessibility of virtual spaces, and recommendations for future virtual programming. DISCUSSION: For youth with disabilities who have been historically marginalized in social spheres, the newly ubiquitous infrastructure regarding virtual programming must be supported and enhanced. A hybrid approach involving virtual/in-person options in future programming is recommended.

Youth with disabilities can benefit from social connections on virtual platforms in terms of physical access to social spaces and opportunities to communicate in alternative waysFor some youth with disabilities, virtual social connections can be the only feasible and readily available option for reducing social isolation due to physical barriers to accessWhen offering virtual program options, service providers should consider the various benefits of connecting with the physical, communication-based, interaction-based, access-based and other barriers to virtual connection.

Acupuncture in Addiction Medicine: Its History, Evidence, and Possibilities.

Substance-use disorders (SUDs) and drug addiction are not only national, but also global health concerns that have worsened during and after the COVID-19 pandemic. Acupuncture augments the endogenous opioid system and, therefore, has a theoretical basis as a treatment for opioid use disorders (OUDs). The basic science of acupuncture, its clinical research in addiction medicine, and decades of success of the National Acupuncture Detoxification Association protocol offer positive findings supporting this protocol's utility for treating SUDs. Considering the mounting opioid/substance-use concerns and deficiencies in SUD treatment availability in the United States, acupuncture can be a safe, feasible treatment option and adjunct in addiction medicine. Furthermore, large governmental agencies are lending support to acupuncture for treating acute and chronic pain, which, in turn, could translate to prevention of SUDs and addictions. This article is a narrative review of the background, the basic science and clinical research, and future direction of acupuncture in addiction medicine.

Social participation interventions targeting relational outcomes for young people with physical and developmental disabilities: an umbrella review and narrative synthesis.

PURPOSE: To synthesize knowledge about social participation interventions targeting relational outcomes for young people with physical and developmental disabilities. METHOD: An umbrella review with a narrative synthesis was conducted to integrate findings of review articles examining social participation interventions targeting relational outcomes (e.g., peer interaction and friendships). Six databases were searched to identify reviews published between 2010 and 2021. RESULTS: Five reviews were identified, examining participation interventions, social/community integration interventions, recreational sport programs, online peer mentorship programs, and augmentative and alternative communication interventions to promote social interaction with peers. Interventions associated with improvements in relational outcomes included group-based programs, programs involving personalized goals, arts-based programs, and multi-component social communication interventions. Recommendations for future research included better description of interventions to identify active ingredients and key mechanisms, measurement of participants' experiences, and the need for interventions to be aligned with the nature of the outcomes examined. Preliminary intervention principles are proposed to guide the design of social participation interventions: individualizing, contextualizing, and immersion in social settings. CONCLUSIONS: There are multiple pathways by which to influence the relational outcomes of young people with disabilities. There are implications for the design of social participation interventions based on an ecological/experiential and relational perspective. IMPLICATIONS FOR REHABILITATIONImprovements in relational outcomes are associated with participation in group-based programs, programs involving personalized goals, arts-based programs, and multi-component social communication interventions.Three evidence-informed principles can help guide the design of social participation interventions: (1) personalizing, (2) contextualizing, and (3) immersion in social settings.Greater attention to aligning the nature of intervention with desired outcomes is needed to more effectively measure and promote relational outcomes.

The creation and implementation of an employment participation pathway model for youth with disabilities.

PURPOSE: Employment participation offers benefits including income, sense of accomplishment, social engagement, and meaningful contribution to society. Rates of competitive employment of youth with disabilities are amongst the lowest in society, despite having capacity and motivation to participate in the workplace. The marginalization of young workers with disability presents a lost opportunity for youth, potential employers, and social care systems. In order to engage young people with disabilities in employment, we present an integrated, community-based model for employment participation preparation. MATERIALS AND METHODS: The employment participation pathway model is based on best available evidence and 15 years of program delivery for youth with disabilities preparing to transition out of school and into employment in the Canadian context. It was conceptualized using the Knowledge to Action framework and presented for consideration in the current paper. RESULTS: Starting early, taking a person-directed approach to planning, and considering the individual and our systems contribute to effective and comprehensive transition to employment. CONCLUSIONS: The employment participation model provides evidence and examples for service providers to consider integrating into their repertoire and begin to construct similar pathways to equip their clients and families with skills, capacities, and knowledge as they journey towards workplace participation.IMPLICATIONS FOR REHABILITATIONEmployment for individuals with disabilities is lower than the national average, with rates being even lower for young people (ages 15-25) with disabilities.Low workplace participation for individuals with disabilities is particularly troubling due to the myriad social and health benefits of engagement in employment.Programs that start early (during high school) and provide ongoing, community-integrated support are reported to be most beneficial to the eventual job attainment and retention for young job seekers with disabilities.The presented employment participation pathway model that was developed using the Knowledge to Action Framework integrates evidence and best practices to support service providers in facilitating progressive workplace participation for clients and families.

Putting Youth in Charge: Exploring a Multi-Year Interagency Community Engagement Experiential Programme for Youth with Disabilities and Their Families.

This paper outlines a qualitative exploration of the experiences of Youth in Charge (YiC), a 3-year pilot programme. YiC was designed to promote early, immersive community participation for students with physical disabilities, and was co-developed/co-hosted by three agencies (hospital, community rehabilitation, school board). To better understand the experiences of the youth, parents, and staff involved in this broad intervention, observation of 10 programme sessions and annual semi-structured interviews with youth (n = 5), parents (n = 4) and staff (n = 6) were undertaken. Qualitative results comprise six themes based in the two major thematic areas of participation-related experiences and programme considerations. Results indicate the need for community-based experiences, measured risk-taking, long-term engagement, parental involvement, and greater interagency collaboration and integration.

A case study of a strategic initiative in pediatric rehabilitation transition services: An insiders' perspective on team principles and practices.

Aims: The aim was to describe an innovative initiative that took place in a pediatric rehabilitation hospital. The goal of this organization-wide strategic initiative, called the Transition Strategy, was to improve service delivery to children/youth with disabilities and their families at times of life transition. The research question was: What are the key elements that have contributed to the success of the Strategy, from the perspective of team members? The objectives were to describe: (a) the guiding principles underlying team functioning and team practices, (b) key enablers of positive team functioning, (c) the nature of effective team practices, and (d) lessons learned. Methods: A holistic descriptive case study was conducted, utilizing historical documents, tracked outcome data, and the experiences and insights of multidisciplinary team members (the authors). Reflecting an insiders' perspective, the impressions of team members were key sources of data. The perspectives of team members were used to generate key teamwork principles, enablers of team functioning, team practices, and key learnings. Findings and Discussion: Team members identified four guiding humanistic principles (respect, support, partnership, and open communication). These principles underpinned three novel practices that contributed to team effectiveness in the eyes of team members: supportive relational practices, human-centered co-design, and solution-focused communication. Key enablers were the relational style of leadership, and a team climate of innovation, autonomy, and trust, supported by the organizational vision. This team climate fostered a sense of psychological safety, thereby encouraging both experimentation and learning from failure. Conclusions: This article provides information for other healthcare organizations interested in understanding the Strategy's value and its implementation. It provides a practical example of how to adopt a humanistic approach to health care, leading to both innovative service development and thriving among team members.

Transitions Theatre: An Arts-Informed Interprofessional Education Workshop.

Introduction: Transition from pediatric to adult care has significant implications for health outcomes in youth with special health care needs. To optimally support the transition, health care and social service providers must work collaboratively with youth and families in service planning, implementation, and evaluation. Based on interviews with 15 youth and their families, we developed an arts-informed interprofessional education activity titled Transitions Theatre using the method of readers' theater. Methods: Three educators with lived experience (one former pediatric rehabilitation client and two parents of youth with special health care needs) and three academic/clinical educators codesigned the transitions. We conducted four online workshops (14-20 participants each). Results: A total of 67 people participated: 59 students from 11 health disciplines and seven postlicensure clinicians and one trainee from five disciplines (e.g., occupational therapy, life skills coaching, early childhood education). Twenty-six participants answered both pre- and postworkshop surveys and reported a positive shift in their understanding of client and family perspectives, their roles in transition support, and other providers' roles in transition support. After the workshop, learners felt more confident with transition support and interprofessional collaboration. The perspectives of the educators with lived experience aligned with the theater scripts and enhanced learners' empathetic engagement with the topic. Discussion: The evidence-based teaching approach of readers' theater and our coteaching model offered learners a unique opportunity to learn about the challenges clients and their families face at the time of transition to adulthood and identify their role in an interprofessional transition support.

Early increase in osteoclast number in mice after whole-body irradiation with 2 Gy X rays.

Bone loss is a consequence of exposure to high-dose radiotherapy. While damage to bone vasculature and reduced proliferation of bone-forming osteoblasts has been implicated in this process, the effect of radiation on the number and activity of bone-resorbing osteoclasts has not been characterized. In this study, we exposed mice to a whole-body dose of 2 Gy of X rays to quantify the early effects of radiation on osteoclasts and bone structural properties. Female C57BL/6 mice (13 weeks old) were divided into two groups: irradiated and nonirradiated controls. Animals were killed humanely 3 days after radiation exposure. Analysis of serum chemistry revealed a 14% increase in the concentration of tartrate resistant acid phosphatase (TRAP)-5b, a marker of osteoclast activity, in irradiated mice (P < 0.05). Osteoclast number (+44%; P < 0.05) and osteoclast surface (+213%; P < 0.001) were elevated in TRAP-stained histological sections of tibial metaphyses. No significant change was observed in osteoblast surface or osteocalcin concentration or in trabecular microarchitecture (i.e. bone volume fraction) as measured through microcomputed tomography (P > 0.05). This study provides definitive, quantitative evidence of an early, radiation-induced increase in osteoclast activity and number. Osteoclastic bone resorption may represent a contributor to bone atrophy observed after therapeutic irradiation.

Electronic media use, reading, and academic distractibility in college youth.

Activities that require focused attention, such as reading, are declining among American youth, while activities that depend on multitasking, such as instant messaging (IMing), are increasing. We hypothesized that more time spent IMing would relate to greater difficulty in concentrating on less externally stimulating tasks (e.g., academic reading). As hypothesized, the amount of time that young people spent IMing was significantly related to higher ratings of distractibility for academic tasks, while amount of time spent reading books was negatively related to distractibility. The distracting nature and the context of IMing in this population are described.

Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy.

PURPOSE: The goal of Pediatric Oncology Group 9243 was to improve outcomes for children with intermediate-risk neuroblastoma (NB). PATIENTS AND METHODS: Patients were assigned to treatments on the basis of age, tumor MYCN status, and tumor cell ploidy. Children in the less intensive arm A received cyclophosphamide/doxorubicin and surgery. Patients not in complete remission postoperatively were treated with cisplatin/etoposide, cyclophosphamide/doxorubicin, and additional surgery. Patients with less favorable features were assigned to arm B, which consisted of carboplatin, etoposide, ifosfamide, and surgery. Survival rates were determined using an intent-to-treat approach. RESULTS: For arm-A patients, the 6-year event-free survival (EFS) was 86% with an SE of 3%. For arm-B patients, the 6-year EFS was 46% with an SE of 7%. MYCN status was the only statistically significant prognostic variable. Among patients whose tumors were MYCN nonamplified, a trend toward improved EFS was seen in children with hyperdiploid versus diploid tumors. However, many of these children responded well to salvage therapy, and overall survival rates did not differ on the basis of ploidy. Six-year EFS rates for arm B were patients with MYCN nonamplified, hyperdiploid tumors, 86% with an SE of 3%; patients with MYCN nonamplified, diploid tumors, 74% with an SE of 10%; patients with MYCN-amplified, hyperdiploid tumors, 46% with an SE of 15%; and patients with MYCN-amplified, diploid tumors, 22% with an SE of 10%. CONCLUSION: Outcomes for patients with MYCN-nonamplified, hyperdiploid tumors were excellent. Therapy reductions for these patients merit study. A trend toward less favorable outcomes for patients with MYCN-nonamplified, diploid tumors was observed; more children may need to be evaluated before therapy is reduced for this subgroup. For patients with MYCN-amplified tumors, new strategies are needed.

Treatment of unresectable and metastatic hepatoblastoma: a pediatric oncology group phase II study.

PURPOSE: To estimate the disease-response rate, proportion of patients whose tumors can be made resectable, event-free survival (EFS), and toxicity in children with unresectable or metastatic hepatoblastoma (HB) after sequential treatment with the following: (1) carboplatin (CARBO); (2) CARBO, vincristine, and fluorouracil (CARBO-VCR-5-FU); and (3) high-dose cisplatin and etoposide (HDDP-ETOP). PATIENTS AND METHODS: Thirty-three assessable patients with stage III (n = 22) and stage IV (n = 11) HB were treated sequentially with one course of CARBO (700 mg/m(2)), followed by three courses of CARBO (700 mg/m(2)), day 0; 5-FU (1,000 mg/m(2)/d), by continuous infusion days 0 to 2; and VCR (1.5 mg/m(2)), days 0, 7, and 14. After that therapy, patients whose tumors were resectable underwent surgery and then received two additional courses of CARBO-VCR-5-FU. Children whose tumors remained unresectable after CARBO-VCR-5-FU or who demonstrated no response or progressive disease during this therapy received two courses of HDDP (40 mg/m(2)/d), days 1 to 5; and ETOP (100 mg/m(2)/d), days 2 to 4. RESULTS: Five-year EFS estimates were 59% +/- 11% for stage III disease (n = 22) and 27% +/- 16% for stage IV disease (n = 11), respectively (P =.037). Twenty-seven (82%) of 33 patients had at least a partial response to chemotherapy; 18 (55%) of 33 responded to CARBO; 24 (80%) of 30 responded to CARBO and CARBO-VCR-5-FU; and nine (75%) of 12 responded to HDDP-ETOP. Surgical resection was achieved in 19 (58%) of 33 patients, including 15 (68%) of 22 stage III patients and four (36%) of 11 stage IV patients. Five-year EFS for patients whose tumors were completely resected was 79% +/- 10%. CONCLUSION: Patients treated sequentially with CARBO, CARBO-VCR-5-FU, and HDDP-ETOP had response rates and EFS comparable to other therapeutic regimens. This regimen is effective in treating localized, unresectable HB and potentially has less toxicity than other regimens. Novel approaches are needed for patients with metastatic disease.

Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study.

PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B). PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children's Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26). RESULTS: For the entire cohort, the 5-year EFS estimate was 19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20% (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P =.78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy. CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.

Use of instant messaging predicts self-report but not performance measures of inattention, impulsiveness, and distractibility.

We examined how young adults' use of instant messaging, text messaging, and traditional reading related to their self-reported experience of distractibility and impulsiveness and to their performance on computerized tasks designed to assess inattention and impulsive responses to visual stimuli. Participants reported their media use and completed self-report measures of impulsiveness (i.e., the Barratt Impulsiveness Scale) and distractibility for academic reading. They also completed performance based measures of inattention and impulsiveness using the Tests of Variables of Attention (T.O.V.A.(®)). Results demonstrated that instant message use was significantly related to higher levels of attentional impulsiveness and distractibility on the self-report measures, while traditional reading consistently predicted lower levels of impulsiveness and distractibility. However, media use was not significantly related to the performance measures of inattention and behavioral impulsiveness.

Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma.

PURPOSE: The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks. The P9645 study was designed to compare the risk of treatment failure for patients with stage III/IV hepatoblastoma randomized to either C5V or CC. METHODS: C5V was given according to INT-0098 and CC consisted of carboplatin at 700 mg/m2 on day 0 (560 mg/m2 after two cycles) followed by cisplatin 100 mg/m2 on day 14. Granulocyte colony-stimulating factor was used after each CC cycle. All patients received four to six cycles of chemotherapy. RESULTS: From the time the study was opened until the time that random assignment was halted, 56 patients received CC and 53 patients received C5V. The 1-year event-free survival was 37% for patients receiving CC and 57% for those receiving C5V (P = .017). Patients randomly assigned to CC required more blood product support. As a result of a semiannual review by the Children's Oncology Group Data and Safety Monitoring Committee, random assignment was discontinued after 3 years of enrollment because the projected improvement in long-term outcome associated with CC was statistically excluded as a possible outcome of this trial. CONCLUSION: Intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma.

Hemolytic uremic syndrome after bone marrow transplantation: clinical characteristics and outcome in children.

Hemolytic uremic syndrome (HUS) is an uncommon but potentially life-threatening complication of hematopoietic stem cell transplantation. We retrospectively studied the medical records of 293 children who underwent allogeneic bone marrow transplantation at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of and to identify risk factors for transplant-associated HUS. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation for patients with hematologic malignancies (n = 244); patients with nonmalignant diseases (n = 49) received disease-specific regimens. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. HUS developed in 28 (9.6%) patients at a median of 171 days after transplantation. We identified older donor age (P = .029), use of antithymocyte globulin in the conditioning regimen (P = .008), and recipient CMV seronegativity (P = .011) as being associated with an increased risk of HUS. With a multiple regression analysis, the use of antithymocyte globulin (beta = .86; P = .04) and recipient cytomegalovirus seronegativity (beta = .93; P = .035) remained significant risk factors for the development of HUS.

Open lung biopsy in pediatric bone marrow transplant patients.

PURPOSE: The aim of this study was to evaluate the clinical benefits of open lung biopsy in the diagnosis and treatment of pulmonary infiltrates in children who have undergone bone marrow transplantation. METHODS: The authors retrospectively reviewed the medical records of all patients in whom pulmonary infiltrates developed within 6 months after bone marrow transplantation. Of 528 patients who received bone marrow transplants (313 allogeneic, 215 autologous) at St Jude Children's Research Hospital between June 1991 and December 1998, 83 (16%) had radiographic evidence of pulmonary infiltrates after the procedure. Of these, 43 (52%) underwent bronchoalveolar lavage (BAL), 19 (23%) underwent open lung biopsy (OLB), 6 (7%) underwent needle biopsy, and 5 (6%) underwent transbronchial biopsy; 21 received medical therapy alone. The authors evaluated the outcome, culture results, histopathologic findings, radiographic findings, and clinical features of those who underwent OLB. RESULTS: The 19 patients ranged in age from 0.9 to 19.8 years (median, 11.4 years). Histopathologic studies indicated an infectious process in 6 patients (30%), bronchiolitis obliterans organizing pneumonia (BOOP) in 5 (26%), interstitial pneumonitis (IP) in 4 (21%), gangliosidosis in 1, and lymphocytic infiltrate in 1. Although the clinical plan was changed on the basis of the histopathologic diagnosis for 17 of the 19 patients (90%), improvement in outcome was seen in only 8 (47.5%) of these patients. Postoperative morbidity (30 days) was 47% and included prolonged intubation (7 patients), pneumothorax (2 patients), and pleural effusion (1 patient). The 30-day survival rate was 63.2% plus minus 10.6%. No patient with multisystem organ failure (MSOF), ventilator dependence, or a postoperative complication survived after OLB. CONCLUSIONS: Histopathologic analysis of OLB specimens is very accurate in determining the cause of pulmonary infiltrates in pediatric patients who have undergone BMT, but OLB may not improve patient outcome. Because the postoperative morbidity and mortality rates associated with OLB are high, careful patient selection is necessary. The mortality rates of patients with MSOF or ventilator dependence are particularly high; therefore, less-invasive alternatives for diagnosis of pulmonary lesions should be considered before OLB is performed.

Nephrotoxicity of iopamidol in pediatric, adolescent, and young adult patients who have undergone allogeneic bone marrow transplantation.

PURPOSE: To assess the effects of the low-osmolar contrast agent iopamidol and antimicrobial drugs on renal function in pediatric, adolescent, and young adult patients who have undergone bone marrow transplantation (BMT). MATERIALS AND METHODS: A retrospective review of records of 120 consecutive pediatric patients who underwent allogeneic BMT in 1997 or 1998 was performed. Eighty-nine patients (median age, 8.1 years) fulfilled study eligibility criteria. Cumulative doses of nephrotoxic antimicrobial drugs were recorded, as well as serum creatinine and blood urea nitrogen concentrations from 24 hours before to 72 hours after each administration of iopamidol during a computed tomographic examination performed within 100 days after BMT. Random coefficient models were used to estimate nephrotoxic effects. RESULTS: Mean baseline glomerular filtration rate was 130.2 mL/min/1.73 m(2), and mean baseline creatinine concentration was 0.51 mg/dL (45 micro mol/L). Older age at BMT (P <.001), use of foscarnet (P =.003), and receipt of iopamidol (P =.073) each prompted a rise in serum creatinine concentration. The antiviral drug foscarnet was associated with the largest increase in the creatinine level; the use of iopamidol effected a relatively small rise in creatinine level. CONCLUSION: Iopamidol nephrotoxicity was negligible in this cohort of pediatric patients who had undergone allogeneic BMT, even in the presence of elevated renal function levels.