Publications by authors named "Danziger-Isakov L"

Pediatric solid organ transplant (SOT) recipients with splenic dysfunction are at increased risk for infections, and tailored guidance on the management of asplenia/hyposplenism among SOT recipients is often lacking. The purpose of this article is to provide practice recommendations via a frequently asked questions (FAQs) format that focuses on three main domains: the identification of asplenia/hyposplenism among SOT recipients/candidates, prophylactic strategies for mitigating the risk of invasive disease associated with splenic dysfunction in the context of transplantation, and the provision of appropriate patient counseling on the risks associated with asplenia/hyposplenism. Answers to the FAQs are based on international expert opinion informed by practices for managing splenic dysfunction and associated data in other populations with asplenia.

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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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  • Coccidioidomycosis is a serious fungal infection that can be transmitted through organ transplantation, with a review of cases from 2013 to 2022 revealing significant risks.
  • Seven deceased donors transmitted the infection to eight recipients, resulting in a 40% infection rate among organ recipients.
  • The study highlights the importance of thorough donor evaluations and antifungal treatment to reduce the high mortality associated with these infections post-transplant.
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Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

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  • - The study aimed to evaluate the effectiveness of short (<120 days) versus long (>180 days) antiviral prophylaxis for preventing cytomegalovirus (CMV) disease in pediatric liver transplant recipients by analyzing data from the Society of Pediatric Liver Transplantation registry between 2015 and 2019.
  • - Among the 199 enrolled participants, shorter prophylaxis resulted in higher occurrences of CMV DNAemia (26.8% vs. 13.8%) and CMV syndrome (18.8% vs. 6.9%) compared to longer prophylaxis, while end-organ disease rates were similar between the two groups.
  • - Long prophylaxis was associated with a significantly higher incidence of neutropenia (55
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Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions.

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Background: Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen.

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Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes.

Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned.

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The Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network focuses on issues related to the transmission of disease through organ transplantation. Providing a review of potential cases of transmission, translating aggregate data into actionable education and guidance for the transplant community, and providing input for policy development, DTAC aims to improve the safety of organ transplantation through a reduction in donor-derived transmission events. Through its nearly 20-year history, DTAC has provided education, guidance, and policy, addressed numerous emerging infections, and continuously focused on the community's understanding of risk assessment related to donor-derived transmission.

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Background: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation.

Aim: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy.

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  • * Strong recommendations include reducing immunosuppression as an initial management step and using the anti-CD20 monoclonal antibody (rituximab), as well as chemotherapy in specific cases.
  • * There is a lack of large randomized phase III trials for treating PTLD in pediatrics, leading to reliance on clinical experience, and the report emphasizes the need for future research on this topic.
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Background: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials.

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Background: Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients.  Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients.

Methods: A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021.

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  • CMV is prevalent in hematopoietic cell and solid organ transplant patients, leading to significant health complications despite current preventive measures.
  • New antiviral medications like Letermovir and Maribavir are changing the options for CMV management; Letermovir is good for prevention but not for treatment, while Maribavir is for treating resistant cases.
  • More research is necessary to understand how these new drugs can effectively and safely be used for CMV in pediatric transplant patients.
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Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019).

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Purpose: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients.

Methods: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines.

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Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs.

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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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  • SARS-CoV-2 infections were common among vaccinated pediatric solid organ transplant recipients (pSOTRs) during the Omicron period, even with strong anti-RBD antibody responses.
  • The findings indicate that while pSOTRs generated good antibody responses, these antibodies had limited effectiveness in neutralizing Omicron subvariants.
  • Breakthrough infections in this group tended to be relatively mild in terms of severity.
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Prevention of donor-derived disease among pediatric solid organ transplant recipients requires judicious risk-benefit assessment. Comprehensive guidelines outline specific donor risk factors and post-transplant monitoring strategies to prevent and mitigate transmission of HIV, hepatitis B, and hepatitis C. However, elimination of unanticipated donor-derived infections remains challenging.

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Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

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Background: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown.

Methods: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart.

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Purpose Of Review: As the volume and complexity of solid organ and hematopoietic stem cell transplantation continue to see rapid growth, the training of a specialized transplant infectious diseases physician workforce is of increasing interest and importance. This review provides an overview of the evolution of transplant infectious diseases training programs, essential elements of training, as well as future needs.

Recent Findings: Despite the first publication of a transplant infectious diseases curriculum in 2010, more recent surveys of infectious diseases trainees have identified gaps in didactic curriculum, donor and recipient assessment, and safe living practices.

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