Publications by authors named "William Otto"

Background: Respiratory infections cause a significant amount of morbidity and mortality in pediatric and young adult patients with malignancy. Bronchoscopy with bronchoalveolar lavage (BAL) is frequently utilized in the diagnostic process, but which patients would most benefit is poorly understood.

Methods: A retrospective study from 2013-2022 examined patients with active malignancy who underwent bronchoscopy with BAL.

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Influenza is a major cause of morbidity and mortality for pediatric cancer patients. We review important aspects in the management of influenza, including virology, epidemiology, clinical presentation, diagnostic testing, and antiviral treatment. Topics that are addressed include optimal treatment of influenza in children with cancer as well as strategies for prevention.

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Article Synopsis
  • Cytomegalovirus (CMV) poses serious health risks for children undergoing transplantation, prompting the need for improved prevention strategies.
  • Current CMV prevention methods have limitations, leading researchers to explore new ways to manage CMV infection, particularly through understanding the role of cell-mediated immunity (CMI).
  • This article reviews how CMI can be leveraged in transplant patients, discusses available CMI assays, and summarizes studies on their effectiveness in preventing and treating CMV infections.
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Background: Treatment of candidemia may be complicated by hematogenous dissemination. Limited data exist to guide decision-making regarding the evaluation for disseminated disease. We sought to describe the epidemiology of invasive disease after candidemia, report the diagnostic evaluations performed and identify risk factors for disseminated disease.

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Background: The upper (URT) and lower (LRT) respiratory tract feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the URT and LRT and explore their relationship with development during childhood.

Methods: We employed V4 16S rDNA sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 183 subjects between 20 weeks and 18 years of age.

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As the field of pediatric transplant infectious diseases continues to grow, new challenges are constantly arising. Advances in immunosuppressive drugs, antimicrobial development, and novel diagnostic tests add new wrinkles to the care of pediatric transplant recipients. This progress in clinical care serves as a call to direct energy toward pediatric transplant infectious diseases research, to better understand how to use these interventions in pediatric practice.

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We review antifungal susceptibility testing and the development of clinical breakpoints, and detail an approach to using antifungal susceptibility results when breakpoints have not been defined. This information may prove helpful when selecting therapy for invasive fungal infections in children.

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Background: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML.

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Background: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period.

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, or raccoon roundworm, is a rare cause of eosinophilic meningoencephalitis with historically poor clinical outcomes. Symptoms of neural larval migrans begin approximately 2-4 weeks after ingestion with fatigue, nausea, fever, and lethargy and then rapidly progress to weakness, incoordination, ataxia, seizures, altered mental status, and finally coma. Only 31 other cases of CNS neural larval migrans have been reported, with more than 25% being lethal.

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We describe ribavirin administration in hospitalized children over an 11-year period. Most patients were immunocompromised; there was variability in ribavirin use across hospitals. There was a clear shift toward the use of oral ribavirin despite a lack of evidence for its use.

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  • Bloodstream infections (BSIs) are common and serious for kids with acute myeloid leukemia (AML), often linked to central venous access devices (CVADs) used during treatment.
  • This study analyzed the risk of bacterial BSIs in pediatric AML patients based on different types of CVADs (tunneled externalized catheter, peripherally inserted central catheter, and totally implanted catheter) using data from over 500 patients.
  • Results showed no significant difference in BSI rates among the CVAD types during neutropenia, suggesting that the risk factors for BSIs may be specific to patients with AML rather than the type of CVAD used.
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Recipients of solid organ and hematopoietic stem cell transplantation undergo substantial immune suppression, placing them at risk for opportunistic viral infection. Few randomized controlled trials have been dedicated to the treatment of viral infections in children, and current practices are extrapolated from data generated from adult patients. Here we discuss the prevention and treatment of viral infections using available antiviral drugs, as well as novel agents that may provide benefit to pediatric patients in the future.

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Article Synopsis
  • The SARS-CoV-2 pandemic has disproportionately affected Black, Hispanic, and other individuals of color, and its impact on non-English-speaking families is less understood.
  • Children with a preferred language other than English showed a significantly higher likelihood of testing positive for SARS-CoV-2 during both the first and second waves of the pandemic.
  • These results highlight the increased risk faced by non-English-speaking families and emphasize the need for action to address systemic inequities contributing to this risk.
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Disseminated toxoplasmosis is an uncommon but highly lethal cause of hyperferritinemic sepsis after hematopoietic cell transplantation (HCT). We report two cases of disseminated toxoplasmosis from two centers in critically ill adolescents after HCT: a 19-year-old who developed fever and altered mental status on day +19 after HCT and a 20-year-old who developed fever and diarrhea on day +52 after HCT. Both patients developed hyperferritinemia with multiple organ dysfunction syndrome and profound immune dysregulation, which progressed to death despite maximal medical therapies.

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Background: Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020.

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Background: In the US, community circulation of the SARS-CoV-2 virus likely began in February 2020 after mostly travel-related cases. Children's Hospital of Philadelphia began testing on 3/9/2020 for pediatric and adult patients, and for all admitted patients on 4/1/2020, allowing an early glimpse into the local molecular epidemiology of the virus.

Methods: We obtained 169 SARS-CoV-2 samples (83 from patients <21 years old) from March through May and produced whole genome sequences.

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Background: Suppurative intracranial complications of sinusitis are rare events in children and can lead to harmful neurologic sequelae and significant morbidity. We sought to review the presentation and management of patients admitted at our hospital with these conditions.

Methods: This was a retrospective study of pediatric patients admitted to a quaternary children's hospital from 2007 to 2019 for operative management of sinusitis with intracranial extension.

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Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease.

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Article Synopsis
  • The text discusses immune-related lung issues and inflammation in severe COVID-19 cases, especially focusing on how a small number of children can experience critical illness during their infection.
  • A panel of pediatric specialists created guidelines for using immunomodulatory therapies for children with severe COVID-19 based on clinical severity and inflammation levels.
  • The recommendations suggest that immunomodulatory therapy is usually not needed for mild cases, but could be beneficial for severe cases, highlighting the importance of evaluating each situation individually and preferring trial-based treatments when possible.
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Background: Understanding the prevalence and clinical presentation of coronavirus disease 2019 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic.

Methods: This was a retrospective case series of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across a pediatric healthcare network, including clinical features and outcomes of those with positive test results.

Results: Of 7256 unique children tested for SARS-CoV-2, 424 (5.

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Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp.

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