Fluoroquinolone Prophylaxis in Children With Cancer: A Pro/Con Discussion.

There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies.

Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment.

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days).

Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers.

From extrachromosomal DNA to neo-peptides, the broad reprogramming of the cancer genome leads to the emergence of molecules that are specific to the cancer state. We recently described orphan non-coding RNAs (oncRNAs) as a class of cancer-specific small RNAs with the potential to play functional roles in breast cancer progression. Here, we report a systematic and comprehensive search to identify, annotate, and characterize cancer-emergent oncRNAs across 32 tumor types.

How I approach: the transplant recipient with fever and pulmonary infiltrates.

Recipients of hematopoietic stem cell transplants and solid organ transplants frequently develop pulmonary infiltrates from both infectious and non-infectious etiologies. Differentiation and further characterization of microbiologic etiologies-viral, bacterial, and fungal-can be exceedingly challenging. Pediatric patients face unique challenges as confirmatory evaluations with bronchoscopy or lung biopsy may be limited.

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

Background: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown.

Methods: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017.

Cerebral chemoarchitecture shares organizational traits with brain structure and function.

Chemoarchitecture, the heterogeneous distribution of neurotransmitter transporter and receptor molecules, is a relevant component of structure-function relationships in the human brain. Here, we studied the organization of the receptome, a measure of interareal chemoarchitectural similarity, derived from positron-emission tomography imaging studies of 19 different neurotransmitter transporters and receptors. Nonlinear dimensionality reduction revealed three main spatial gradients of cortical chemoarchitectural similarity - a centro-temporal gradient, an occipito-frontal gradient, and a temporo-occipital gradient.

An 11-Year Review of Lactobacillus Bacteremia at a Pediatric Tertiary Care Center.

Objectives: To inform clinical decisions on the use of probiotics in a pediatric inpatient setting, we sought to determine the number of cases of Lactobacillus bacteremia as well as associated patient characteristics in a tertiary-care pediatric hospital over an 11-year period.

Methods: Cases of Lactobacillus bacteremia among admitted patients were identified through positive blood culture reports. The clinical chart for each case was reviewed for presenting symptoms and risk factors such as probiotic use, presence of a central venous catheter, immunocompromised state, impaired intestinal function, and age below 3 months.

Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei.

Variant surface glycoprotein (VSG) coats bloodstream form Trypanosoma brucei parasites, and monoallelic VSG expression underpins the antigenic variation necessary for pathogenicity. One of thousands of VSG genes is transcribed by RNA polymerase I in a singular nuclear structure called the expression site body (ESB), but how monoallelic VSG transcription is achieved remains unclear. Using a localization screen of 153 proteins we found one, ESB-specific protein 1 (ESB1), that localized only to the ESB and is expressed only in VSG-expressing life cycle stages.

A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays.

Impact of Oxidative Stress on Risk of Death and Readmission in African Children With Severe Malaria: A Prospective Observational Study.

Background: We hypothesized that oxidative stress in Ugandan children with severe malaria is associated with mortality.

Methods: We evaluated biomarkers of oxidative stress in children with cerebral malaria (CM, n = 77) or severe malarial anemia (SMA, n = 79), who were enrolled in a randomized clinical trial of immediate vs delayed iron therapy, compared with community children (CC, n = 83). Associations between admission biomarkers and risk of death during hospitalization or risk of readmission within 6 months were analyzed.

COVID-19 Patient Vaccine Program Design and Implementation: An Academic Children's Hospital's Model, Approach, and Outcomes.

To slow the spread of the 2019 novel coronavirus disease (COVID-19) and reduce the associated morbidity and mortality, the Children's National Hospital developed a multidisciplinary, collaborative vaccine program aimed at equitably and expeditiously vaccinating the pediatric population of the surrounding community. Interdepartmental collaboration, professional expertise, and community partnerships allowed for a dynamic and successful program design that began as large volume-centralized vaccine clinics and expanded to smaller volume ambulatory clinics. This strategy proved successful at meeting local vaccine demand; however, strategies to improve vaccine uptake in communities with high rates of hesitancy are still needed to maximize vaccine equity.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

Background: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis.

Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites.

Safety and Tolerability of Monoclonal Antibody Therapies for Treatment of COVID-19 in Pediatric Patients.

There is a little data regarding safety or efficacy of monoclonal antibody treatment for mild-to-moderate COVID-19 in pediatric patients despite it being frequently used in adults. This retrospective study of 17 patients with mild-to-moderate COVID-19 who received monoclonal antibody therapy found that the treatment was well tolerated, safe, and may be effective in halting progression to severe disease.

A prometastatic splicing program regulated by SNRPA1 interactions with structured RNA elements.

Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report a systematic effort to decipher the RNA structural code that shapes pathological splicing during breast cancer metastasis. We discovered a previously unknown structural splicing enhancer that is enriched near cassette exons with increased inclusion in highly metastatic cells.

Complexities of Zika Diagnosis and Evaluation in a U.S. Congenital Zika Program.

The objective of the study was to describe the complexity of diagnosis and evaluation of Zika-exposed pregnant women/fetuses and infants in a U.S. Congenital Zika Program.

β-Lactamase-Producing, Ciprofloxacin-Resistant Neisseria meningitidis Isolated From a 5-Month-Old Boy in the United States.

Worldwide, there have been few reports of β-lactamases causing penicillin resistance in Neisseria meningitidis. The first known case of disease in the United States due to a β-lactamase-producing, ciprofloxacin-resistant N. meningitidis was recently identified.

Approaches to safe living and diet after solid organ transplantation.

SOT recipients are at high risk for developing severe infectious complications following discharge from the hospital. Comprehensive anticipatory guidance surrounding everyday lifestyle choices can potentially prevent exposure to infectious agents from the environment. This paper reviews the risks that pediatric and adolescent SOT recipients encounter through exposures such as household contacts, outdoor activities, travel, animal exposures, and dietary choices.

Impact of hospital acquired infections on post-transplant one year mortality in pediatric bone marrow transplant patients.

Objective: Children undergoing hematopoietic stem cell transplant (HSCT) are prone to infections, especially when hospitalized for the transplant or additional medical care. These infections are perceived to increase patient's mortality risk, but data are lacking. We conducted this study to assess the burden and the impact of hospital acquired infections (HAI) on mortality risk among pediatric HSCT patients.

RBMS1 Suppresses Colon Cancer Metastasis through Targeted Stabilization of Its mRNA Regulon.

Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor of colon cancer progression.

Future avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery.

When Alzheimer's disease (AD) disease-modifying therapies will be available, global healthcare systems will be challenged by a large-scale demand for clinical and biological screening. Validation and qualification of globally accessible, minimally-invasive, and time-, cost-saving blood-based biomarkers need to be advanced. Novel pathophysiological mechanisms (and related candidate biomarkers) - including neuroinflammation pathways (TREM2 and YKL-40), axonal degeneration (neurofilament light chain protein), synaptic dysfunction (neurogranin, synaptotagmin, α-synuclein, and SNAP-25) - may be integrated into an expanding pathophysiological and biomarker matrix and, ultimately, integrated into a comprehensive blood-based liquid biopsy, aligned with the evolving ATN + classification system and the precision medicine paradigm.