Pediatric Patients Research Articles

Precision genome profiling for pediatric leukemia with a software-controlled enrichment method using nanopore sequencer.

10027 Background: The real-time nature of nanopore sequencing allows for simultaneous basecalling of DNA sequences during sequencing. This unique capability enables adaptive sampling (AS), a software-controlled targeted sequencing method. AS is notable for its ability to rapidly and flexibly enrich multiple genes with long fragment reads and detect various modalities of genetic aberrations in a single run. However, the feasibility and significance of AS for cancer have not been previously reported. Methods: We performed AS on a GridION sequencer using samples from 28 pediatric leukemia patients (10 acute myeloid leukemia, 13 B-cell acute lymphoblastic leukemia, and 5 T-cell acute lymphoblastic leukemia). Target regions were comprised of 466 genes associated with hematologic malignancies and included 30-kilo base pairs of flanking regions. After 3 days of sequencing, single-nucleotide variants (SNVs), structural variations (SVs), and copy number variations (CNVs) were determined. In 21 samples, variant calling accuracy was evaluated using short-read-based whole genome sequencing (WGS). Results: In the on-target regions, mean depth was 21.0× and N50 was 11,191 bps at the median. Of the 13 samples with genetic alterations previously detected through clinical testing for diagnostic classifications, all were reconfirmed by AS. Detecting DUX4 rearrangement needed an additional analysis pipeline because of its structural complexity. Among the 15 remaining samples whose genetic alterations had not been determined by clinical diagnostic testing, AS identified putative driver aberrations in 14 samples. All of these genomic abnormalities were structural variations (SVs) or copy number variations (CNVs), most of which were not encompassed within the genes or regions targeted in clinical diagnostic testing. Detected SVs were described with accurate genomic breakpoints, enabling the efficient detection of gene rearrangements and deletions of the entire region of an exon or a gene. Regarding CNVs, both chromosomal-level CNVs, such as high-hyperdiploid, and focal CNVs, such as CDKN2A deletion, were detectable using genome-wide low-coverage reads in the off-target regions. In the other case with acute myeloid leukemia in which genetic abnormalities were not detected either by clinical testing or AS, WGS identified an NPM1 frameshift deletion located outside of known hotspots. Among variants identified by WGS, AS detected 60.9% of the SNVs, 17.6% of the small indels, and 89.2% of the SVs, with a tendency of poor detection efficiency for variants with low variant allele frequency. Conclusions: AS provides a rapid and precise description of the genomic profile of pediatric leukemia, particularly advantageous for identifying SVs and CNVs, which are difficult to detect by capture-based short-read sequencing.

Outcome of Beta Thalassemia Major in Paediatric Patients Allografted from Fully Matched Related Donors; in Egypt

Outcome of Beta Thalassemia Major in Paediatric Patients Allografted from Fully Matched Related Donors; in Egypt

New Kid on the Block: A Systematic Review of the Quadratus Lumborum Block in Plastic and Reconstructive Surgery.

Although the transversus abdominal plane (TAP) block is commonly used in abdominal surgery as part of enhanced recovery after surgery pathways, the quadratus lumborum (QL) block has been hypothesized as an effective alternative to the TAP block in some areas. This review evaluates the current literature, as it relates to the QL block in plastic and reconstructive surgery. A systematic review using PubMed searched for all original, peer-reviewed articles, including the term "quadratus lumborum block." In total, 509 articles were identified for review by two independent reviewers. Original articles evaluating the use of a QL block in any plastic surgery operation were included. Articles evaluating pediatric patients, animal trials, and the use of a QL block in any nonplastic surgery operation were excluded. Three articles met inclusion criteria. One trial demonstrated decreased subjective pain scores and total opioid use, whereas the second found no statistically significant difference. A case study described the use of a QL block for unilateral breast reconstruction with minimal opiate use and reduced pain scores postoperatively. Limitations include the limited number of studies and the heterogeneity in study type and design, making analysis difficult. Despite its demonstrated efficacy in other surgical subspecialties, there are limited data evaluating the use of the QL block in plastic and reconstructive surgery. Additional research is needed to evaluate the role of the QL block in plastic surgery and how it compares to the more widely utilized TAP block.

New Technology, Warm Care: Social Robots in Nursing Practice and Research

Recent, rapid advancements in technology have enabled the introduction and integration of robots into everyday life. Different from the traditional image of robots as cold and mechanical, social robots are designed to emulate human interaction patterns, improving the user experience and facilitating social interactivity. Thus, social robots represent a promising new care intervention. In this article, after defining social robots and explaining the factors influencing "human-robot interaction", the authors discuss the effectiveness of social robots in the context of providing care to patients with dementia and autism as well as to pediatric patients. Finally, current cases in which PARO, a social robot, has been used in nursing are described, and key challenges and suggestions for future social robot applications are given. Current evidence indicates social robots must be developed and designed to adhere to a people-centered approach to achieve better robot-assisted care outcomes, be better accepted by patients, and better enable patients to open up emotionally and maintain good physical, mental, and social well-being.

Risk factors associated with wheezing in severe pediatric community-acquired pneumonia: a retrospective study.

Wheezing is a common clinical manifestation in children with pneumonia. However, the risk factors associated with the development of wheezing pneumonia and its clinical features are not fully characterized, especially in children with severe pneumonia. We retrospectively recruited 1434 pediatric patients diagnosed with severe pneumonia between April 2012 and September 2019 in Fujian Maternity and Child Health Hospital. The medical records regarding demographic information, clinical manifestations, radiographic/laboratory findings, and complications were collected. Based on the presence or absence of wheezing symptoms and signs, subjects were divided into wheezing cohort (N.=684) and non-wheezing cohort (N.=750), and their clinical data were compared. Multivariate cox regression analysis was performed to identify independent risk factors of wheezing. Demographic features including gender, weigh, onset season, birth weight, full-term birth or not, history of pneumonia were significantly associated with the occurrence of wheezing in severe CAP (P<0.05). Specifically, male gender, onset seasons in autumn/winter, and absence of a history of pneumonia were identified as independent risk factors of wheezing in multivariate analysis (P<0.05). As for clinical features, wheezing cohort differed from the non-wheezing one in terms of clinical manifestation (higher incidence of cough and breathless, but lower incidence of fever), laboratory finding (higher levels of red blood cells, hemoglobin, and albumin and lower levels of total or indirect bilirubin and creatine), pathogen detection (higher incidence of respiratory syncytial viral infection), and clinical complications (lesser risk of sepsis and hydrothorax) (P<0.05). Severe CAP with wheezing is a special clinical entity of severe pneumonia in children, which has specific risk factors and differ from non-wheezing pneumonia in terms of clinical features and etiologic pathogens.

Primary intracranial germ cell tumors in adolescents and adults: Results of an international, multicenter, retrospective cohort study.

2061 Background: Primary Intracranial Germ Cell Tumors (iGCT) are rare. Previous prospective and retrospective studies mainly included pediatric patients (pts) with a median age of 10-14 years. The aim of this retrospective analysis was to evaluate characteristics, treatment and outcome of adolescents and adults with iGCT. Methods: Data were collected from 10 institutions in Germany and Switzerland. Pts aged &gt;/= 16 years at first diagnosis or at relapse with a primary iGCT were included. Objective responses were evaluated by local investigators. Statistics (Cox proportional hazard model, progression-free survival (PFS) and overall survival (OS) analyzed by Kaplan-Meier method) were performed with SPSS v29. Results: We identified 75 pts (92.0% male) with a median age of 23 years (range 16-60, 94.7% &gt;/= 18 years). At first diagnosis, histology was pure germinoma in 70.7%, pure teratoma in 10.7%, other non-germinomatous GCT (NGGCT) in 13.3%, unknown in 5.3% of pts. Localized, bifocal, and metastatic disease was found in 72.0, 6.7, and 21.3% of pts. As part of their first line (1L) treatment, 69.3%, 80.0%, and 62.7% received surgery, radiotherapy, and chemotherapy, respectively. High dose chemotherapy/ autologous stem cell transplantation (HDCT/ASCT) was part of 1L treatment in n=3 pts with NGGCT. Trimodal and bimodal treatment was performed in 48.0% and 32.0% of pts. Response to 1L therapy was complete remission (CR) in 61.3%, partial remission tumor marker negative (PRm-) in 16.0%, PRm+ in 4.0%, PR with tumor marker status unknown in 4.0%, progressive disease (PD) in 2.7%, and unknown in 12.0%. Relapse occurred in 13/75 pts (17.3%) with unknown histology (n=4), teratoma (n=2), other NGGCT (n=4), and germinoma (n=3). In 2 pts. in whom germinoma was diagnosed at time of first diagnosis, at time of recurrence PNET and Yolk sac tumor were histologically proven. Median time to relapse was 19.0 months (mo.; range 3-223). HDCT/ASCT as salvage treatment was performed in 5 pts with NGGCT and in one pt with germinoma as 2L (n=5) or 3L (n=1). NGGCT histology was associated with increased risk for recurrence or death (p=0.012 and 0.039).3-year PFS was 90.7% (germinoma: 98.1%, NGGCT: 73.9%) and 5-year OS was 92.0% (germinoma: 98.1%; NGGCT: 78.3%). Median follow-up time was 60 mo (range 0-339). Conclusions: Disease characteristics, treatment and outcomes of adolescent/ adult iGCT pts are comparable to those reported in pediatric pts. High cure rates are achieved in pts with pure germinoma and current treatment concepts. In pts with NGGCT further investigation is needed to improve survival outcomes.

Implementing Inpatient Social Needs Screening in an Urban Tertiary Care Children's Hospital.

The American Academy of Pediatrics recommends screening for unmet social needs, and the literature on inpatient screening implementation is growing. Our aim was to use quality improvement methods to implement standardized social needs screening in hospitalized pediatric patients. We implemented inpatient social needs screening using the Model for Improvement. An interprofessional team trialed interventions in a cyclical manner using plan-do-study-act cycles. Interventions included a structured screening questionnaire, standardized screening and referrals workflows, electronic health record (EHR) modifications, and house staff education, deliberate practice, and feedback. The primary outcome measure was the percentage of discharged patients screened for social needs. Screening for social needs was defined as a completed EHR screening questionnaire or a full social work evaluation. Process and balancing measures were collected to capture data on screening questionnaire completion and social work consultations. Data were plotted on statistical process control charts and analyzed for special cause variation. The mean monthly percentage of patients screened for social needs improved from 20% at baseline to 51% during the intervention period. Special cause variation was observed for the percentage of patients with completed social needs screening, EHR-documented screening questionnaires, and social work consults. Social needs screening during pediatric hospitalization can be implemented by using quality improvement methods. The next steps should be focused on sustainability and the spread of screening. Interventions with greater involvement of interdisciplinary health care team members will foster process sustainability and allow for the spread of screening interventions to the wider hospitalized pediatric population.

Predicting Adherence to Topical Medications in Chronic Rhinologic Disease: A Systematic Review.

To determine risk factors of medical adherence and describe strategies to increase adherence in patients with chronic rhinologic disease. PubMED, SCOPUS, CINAHL, and Cochrane. Systematic review of 4 databases (PubMED, SCOPUS, CINAHL, Cochrane) from inception of databases to September 1, 2022 to identify studies that evaluated factors related to and affected by medical adherence in patients with chronic rhinologic disease. Of 1491 studies screened, 25 studies met inclusion criteria. Of these, 7 studies described how sensory attributes of intranasal sprays affect adherence, including odor, taste, aftertaste, and side effects. Five studies described record keeping diaries/notification systems to improve adherence, with demonstration of web-based platforms to send reminders as well as keep record of medication usage to improve adherence. Eight studies described patient-specific risk factors to nonadherence, with demonstration of increased age and conscientious personalities correlating with medical adherence. Five studies looked at pediatric patients specifically, with adherence rates in children parallelling that of adults. Additionally, nonadherence in children may have greater implications for school performance. Overall, adherence to topical medical therapy in patients with chronic rhinologic disease is affected by patient-related and medication-specific factors which should be considered when counseling patients. Web-based diary or notification systems may help increase adherence. Additionally, children are equally adherent to topical medical therapy as adults and nonadherence may have negative implications for school performance.

Impact of breaks in therapy on survival for pediatric patients with relapsed or refractory solid tumors: A single-center study.

10021 Background: Relapsed or refractory (R/R) solid tumors remain a significant cause of mortality for children. While upfront therapies have been well-studied, the cumulative effects of multiple relapses and salvage regimens is unknown. We describe the disease trajectory in these patients, from the time of first R/R event (on-therapy progression/refractoriness or off-therapy relapse) to time of death or last follow-up. We also analyze whether breaks ( &gt; 30 days) between diagnosis of events and initiation of subsequent therapies have an impact on survival. Methods: We reviewed data from electronic medical records for patients with primary, malignant R/R extracranial solid tumors treated at Texas Children’s Hospital between 2005-2023. Descriptive analysis was performed along with univariate chi-square, one-way ANOVA, and independent sample t-tests. Cox regression analysis was used to evaluate time from first event to death or last known follow-up for each variable described. Analysis was performed with SPSS v29. Results: We reviewed data for 466 patients with R/R solid tumors (female: 47%; median age: 8.66 years; median follow-up after first event: 12.9 months). Most common diagnoses were neuroblastoma (21.5%), rhabdomyosarcoma (19.1%), and osteosarcoma (16.1%). Patients had a median of 3 (interquartile range [IQR]: 1-4) R/R events with a median of 93 (IQR 52-200) days between each event. The most common post-event therapy regimens were intravenous chemotherapy alone (21.4%) or in combination with surgery and/or radiotherapy (19.9%). Deceased patients (n = 339) had a median of 291 (IQR: 127-549) days from first event to death. Increased time from first R/R event to death was associated with a break in disease-directed therapy; type of diagnosis; non-metastatic stage at original diagnosis; type of first event; type of first salvage regimen; and receiving phase 1 therapy. Of 438 patients who received ≥1 salvage therapy regimen, 116 (26.5%) took ≥1 break between an R/R event and subsequent therapy. Reasons for breaks varied relatively evenly between intentional/goal-concordant (e.g., to seek second opinion, to focus on quality of life), and unintentional (e.g., care coordination, care access issues). In a multivariable Cox regression model, taking a &gt; 30 day break in disease-directed therapy was associated with prolonged survival, even after adjusting for number of events and significant covariates (p &lt; 0.05). Conclusions: The prognosis for children with R/R solid tumors is poor. Most children experience multiple R/R events and therapy regimens without a break in therapy. Presence of a &gt; 30 day break between an R/R event and subsequent therapy did not negatively impact survival, implying that time between therapy regimens can safely be offered to some patients to promote quality of life, exploration of goals of care, and thoughtful decision-making, without compromising survival.

TAZNI: A phase I/II combination trial of tazemetostat with nivolumab and ipilimumab for children with INI1-negative or SMARCA4-deficient tumors.

TPS10077 Background: The prognosis for children with INI1-negative cancers is dismal, with historic 5-year overall survival &lt;30%. These cancers (including malignant rhabdoid tumors [MRT], atypical teratoid rhabdoid tumors [ATRT], epithelioid sarcomas [ES], and poorly differentiated chordomas) have few novel treatment options. These tumors exhibit a heightened dependence on the Polycomb Repressive Complex, whereby EZH2 is the catalytic subunit. Two recent pediatric phase 1/2 trials with EZH2 inhibitor tazemetostat (EZH-102, NCT02601937 and APEC1621C, NCT03213665) demonstrated 17% overall objective response rate, with 19% response in ATRT patients and higher response rates in patients with chordoma and ES. One patient had PR on the phase 2 Pediatric MATCH study and 5 patients had prolonged SD. Studies of INI1-deficient tumors have shown significant immune infiltration, including T-cells with high levels of inhibitory checkpoint receptors. As EZH2 has a role in tumor immunity and tazemetostat increases MHC presentation and immune signaling, we hypothesized that combining EZH2 inhibitor with checkpoint inhibitors may provide benefit for pediatric patients with INI1- or SMARCA4-deficient tumors. Methods: TAZNI is a phase 1/2, multi-center trial of Tazemetostat, Nivolumab and Ipilimumab for children with INI1- or SMARCA4-deficient tumors after upfront therapy. All patients receive standard pediatric nivolumab and ipilimumab doses/dosing schedule with continuous tazemetostat dosing determined by disease strata: Stratum A- subjects with ATRT; Stratum B for all other (non-ATRT) INI1/SMARCA4-deficient tumors. Each stratum is subdivided by disease status: A1/B1- subjects with refractory disease after upfront therapy; A2/B2- subjects with relapsed disease; and A3/B3: subjects with no evidence of disease (NED) after upfront therapy. The study is conducted in 2 parts: Part 1 will be two concurrent “rolling six” phase 1 studies to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) by disease stratum. Starting dose level 1 for Stratum A is 900mg/m2 orally BID and for Stratum B: 520mg/m2 orally BID, with one dose escalation and one dose de-escalation planned. Part 2 will be two phase 2 studies to estimate the overall response rate (ORR) in Substrata A1 and A2 (with refractory disease or with relapse, respectively), based on a primary endpoint of ORR (CR+PR) in a Simon’s 2-stage design at the RP2D. All other substrata will be descriptive analyses. Patients may receive up to 26 cycles of therapy. Key inclusion/exclusion criteria include INI1 loss by immunohistochemistry (IHC) or molecular confirmation; age between 6 mo and 21 yo; no prior immunotherapy; limited corticosteroid; and no history or concern for hematologic malignancy. To date, 4 patients have enrolled, and the study is ongoing in the United States. Clinical trial information: NCT05407441 .

Impact of Continuous Renal Replacement Therapy Initiation Time, Kidney Injury, and Hypervolemia in Critically Ill Children.

The mortality rate of pediatric patients who require continuous renal replacement therapy is approximately 42%, and outcomes vary considerably depending on underlying disease, illness severity, and time of dialysis initiation. Delay in the initiation of such therapy may increase mortality risk, prolong intensive care unit stay, and worsen clinical outcomes. In the pediatric intensive care unit of an urban level I trauma children's hospital, continuous renal replacement therapy initiation times and factors associated with delays in therapy were unknown. This quality improvement process involved a retrospective review of data on patients who received continuous dialysis in the pediatric intensive care unit from January 1, 2017, to December 31, 2021. The objectives were to examine the characteristics of the children requiring continuous renal replacement therapy, therapy initiation times, and factors associated with initiation delays that might affect unit length of stay and mortality. During the study period, 175 patients received continuous renal replacement therapy, with an average initiation time of 11.9 hours. Statistically significant associations were found between the degree of fluid overload and mortality (P < .001) and between the presence of acute kidney injury and prolonged length of stay (P = .04). No significant association was found between therapy initiation time and unit length of stay or mortality, although the average initiation time of survivors was 5.9 hours shorter than that of nonsurvivors. Future studies are needed to assess real time delays and to evaluate if the implementation of a standardized initiation process decreases initiation time.

Preclinical efficacy of BRG1/BRM ATPase inhibitor in B lymphoblastic leukemia.

10030 Background: Acute lymphoblastic leukemia (ALL) is the most common blood cancer in children and young adults. While ALL has a high cure rate, approximately 20% of patients who initially respond to treatment relapse and prognosis post relapse remains poor. New therapeutic treatments are needed to reduce relapse rates in B-ALL pediatric patients and to minimize the toxic side effects seen with current therapies. We and others have previously shown that BRG1/BRM ATPase inhibitors have efficacy in targeting acute myeloid leukemia (AML) and one, FHD-286, is currently being evaluated for its use in AML in an ongoing clinical trial (NCT04891757). BRG1 and BRM are the ATP-dependent catalytic subunits of the SWI/SNF chromatin remodeling complex which has a critical role in controlling gene expression, cell growth and survival of AML cells. Our prior work revealed that BRG1/BRM ATPase inhibition leads to selective transient reduction of normal B cells. Further, data from Depmap also nominates SMARCA4, the gene encoding BRG1, as a dependency in B-ALL cell lines, leading us to hypothesize that BRG1/BRM inhibition may be an effective therapy for B-ALL. Methods: We treated B-ALL cell lines with varying genetic lesions ( KMT2A-rearranged: RS4;11, KOPN-8, SEM; ETV6::RUNX1 fusion: REH and DUX4-rearranged: Nalm6) with dose titrations of FHD-286 and measured cell growth over the course of six days. In addition, at 48- and 72-hours post-treatment, we assayed cells for viability, cell cycle kinetics, and apoptosis induction via flow cytometry to provide insight into FHD-286’s mechanism of action in B-ALL. Results: We found that FHD-286 treatment resulted in decreased cell growth in a dose-dependent manner across all B-ALL cell lines. While all cell lines were displayed reduced proliferation at nanomolar doses, sensitivity varied. Nalm6, REH and SEM cells were the most sensitive with low nanomolar IC50s (2-7nM). In contrast, two of the KMT2Ar B-ALL lines, RS4;11 and KOPN-8, required higher doses to achieve growth inhibition (40-70nM). To better understand the mechanism by which FHD-286 is affecting cell growth, we evaluate whether FHD-286 is targeting cell growth through the apoptotic pathway or through cell cycle arrest. Our preliminary data indicates cell growth inhibition is only slightly attributable to cell cycle arrest and apoptosis induction, leading us to explore terminal differentiation as a mechanism of slowed proliferation. Conclusions: Our results show FHD-286 can strongly inhibit B-ALL cell growth in vitro, indicating FHD-286 as a potential therapeutic agent to treat B-ALL. In vivo validation is ongoing. Further directions include defining the effect of FHD-286 on chromatin remodeling, gene expression, and exploring efficacy in combination therapy, which has been shown to increase FHD-286 efficacy against AML. Our data may ultimately justify inclusion of B-ALL patients in clinical studies of BRG1/BRM inhibitors.

Percutaneous thermal radiofrequency rhizotomy of L2-S1 spinal nerve roots in children with cerebral palsy.

This study presents the results of an evaluation of the effectiveness of percutaneous thermal radiofrequency (RF) ablation of spinal nerve roots to reduce spasticity and improve motor function in children with cerebral palsy (CP). A retrospective analysis was conducted on the surgical treatment outcomes of 26 pediatric patients with severe CP (Gross Motor Function Classification System levels IV-V). The assessment protocol included muscle tone assessment using the modified Ashworth scale (MAS), evaluation of passive and active range of motion, gait video recording, and locomotor status evaluation using the Gross Motor Function Measure (GMFM)-88 scale. Thermal RF rhizotomy (ablation of spinal nerve roots) was performed on all patients at the L2-S1 levels at 70°C for 90 seconds. The statistical data analysis was conducted using the t-test and Mann-Whitney U-test. A p value < 0.05 was considered statistically significant. Before the operation, the average level of spasticity in the lower-limb muscles of all patients was 3.0 ± 0.2 according to the MAS. In the early postoperative period, the spasticity level in all examined muscle groups significantly decreased to a mean of 1.14 ± 0.15 (p < 0.001). In the long-term postoperative period, the spasticity level in the examined muscle groups averaged 1.49 ± 0.17 points on the MAS (p < 0.001 compared to baseline, p = 0.0416 compared to the early postoperative period). Despite the marked reduction of spasticity in the lower limbs, no significant change in locomotor status according to the GMFM-88 scale was observed in the selected category of patients. In the long-term period, during the control examination of patients, the GMFM-88 level increased on average by 3.6% ± 1.4% (from 22.2% ± 3.1% to 25.8% ± 3.6%). The findings of this study offer preliminary yet compelling evidence that RF ablation of spinal nerve roots can lead to a significant and enduring decrease in muscle tone among children with severe spastic CP. Further studies and longer-term data of the impact on functionality and quality of life of patients with CP after spinal root RF ablation are needed.

A Spatiotemporal Deep Learning Framework for Scalp EEG-Based Automated Pain Assessment in Children.

Common pain assessment approaches such as self-evaluation and observation scales are inappropriate for children as they require patients to have reasonable communication ability. Subjective, inconsistent, and discontinuous pain assessment in children may reduce therapeutic effectiveness and thus affect their later life. To address the need for suitable assessment measures, this paper proposes a spatiotemporal deep learning framework for scalp electroencephalogram (EEG)-based automated pain assessment in children. The dataset comprises scalp EEG data recorded from 33 pediatric patients with an arterial puncture as a pain stimulus. Two electrode reduction plans in line with clinical findings are proposed. Combining three-dimensional hand-crafted features and preprocessed raw signals, the proposed transformer-based pain assessment network (STPA-Net) integrates both spatial and temporal information. STPA-Net achieves superior performance with a subject-independent accuracy of 87.83% for pain recognition, and outperforms other state-of-the-art approaches. The effectiveness of electrode combinations is explored to analyze pain-related cortical activities and correspondingly reduce cost. The two proposed electrode reduction plans both demonstrate competitive pain assessment performance qualitatively and quantitatively. This study is the first to develop a scalp EEG-based automated pain assessment for children adopting a method that is objective, standardized, and consistent. The findings provide a potential reference for future clinical research.

A rare case of self-inflicted foreign body in the urethra of a pediatric patient which was successfully managed with urethrotomy converted into urethrostomy: a case report

A rare case of self-inflicted foreign body in the urethra of a pediatric patient which was successfully managed with urethrotomy converted into urethrostomy: a case report

Discharge Under Sedated Status can Decrease Postoperative Emergence Agitation in Pediatric Patients Undergoing Strabismus Surgery: A Prospective Randomized Controlled Trial

Discharge Under Sedated Status can Decrease Postoperative Emergence Agitation in Pediatric Patients Undergoing Strabismus Surgery: A Prospective Randomized Controlled Trial

Cost-effectiveness of single-day intravenous fosaprepitant versus three-day oral aprepitant anti-emetic regimen in pediatric patients receiving highly-emetogenic chemotherapy.

10075 Background: The non-inferiority of single-dose fosaprepitant to a three-day oral aprepitant-based anti-emetic regimen for pediatric patients receiving high emetogenic chemotherapy (HEC) has not been demonstrated. The cost-effectiveness of these regimens with respect to each other in India and the United States (US) is unknown. Methods: Individual patient data from an investigator-initiated, open-label, non-inferiority randomized control trial was used to estimate health states. The total costs and quality-adjusted life years (QALY) were calculated from the patient's perspective in India and the US. The incremental-cost utility ratio (ICUR) and net-monetary benefit (NMB) were calculated. One-way sensitivity analysis was done by varying the cost of medications, hospitalization and utility values by ±25%. Results: The fosaprepitant arm had a total QALY of 0.0116 compared to 0.0118 in the aprepitant arm. The use of fosaprepitant led to an incremental cost of $14.21 in India and a cost reduction of $193.81 in the US. The total cost of medication in the fosaprepitant arm was higher in India and lower in the US compared to the aprepitant arm. The cost of hospitalisation was lower in the fosaprepitant in both India and the US. The ICUR was -$59,974.86/QALY in India and $817,737.23/QALY in the US. The ICUR for India was located in the north-west quadrant of the cost-effectiveness plane, for the US it was located in the south-west quadrant below the willingness the pay threshold for the US. The ICUR estimate was most sensitive to the cost of fosaprepitant in India and the utility value of the complete protection health state in the US. Conclusions: Fosaprepitant was not found to be cost-effective versus aprepitant in India, comparatively it was cost-saving and cost-effective in the US. These findings highlight the necessity of region-specific considerations when evaluating the cost-effectiveness of anti-emetic regimens. [Table: see text]

An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer.

Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy. For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, and tested it with cell lines and noncancer control blood samples. We then used this panel to analyze whole-blood samples for CTC burden with a cohort of 15 patients with hepatoblastoma and HCC and correlated with patient characteristics and outcomes. We showed that ICG accumulation is specific to liver cancer cells, compared to nonmalignant liver cells, non-liver solid tumor cells, and other nonmalignant cells, and can be used to identify liver tumor cells in a mixed population of cells. Experiments with the ICG/Glypican-3/DAPI panel showed that it specifically tagged malignant liver cells. Using patient samples, we found that CTC burden from sequential blood samples from the same patients mirrored the patients' responses to therapy. Our novel ICG-based liquid biopsy test for CTCs can be used to specifically detect and quantify CTCs in the blood of pediatric patients with liver cancer.

Differential Inflammatory Responses in Adult and Pediatric COVID-19 Patients: Implications for Long-Term Consequences and Anti-Inflammatory Treatment.

BACKGROUND COVID-19 manifests with varying degrees of severity across different age groups; adults typically experience more severe symptoms than children. Matrix metalloproteinases (MMPs), known for their role in tissue remodeling and immune responses, may contribute to the pathophysiological disparities observed between these groups. We sought to delineate differences in serum MMP profiles between adult and pediatric COVID-19 patients, assess the influence of anti-inflammatory treatment on MMP levels, and examine potential implications for long-term consequences. MATERIAL AND METHODS Serum samples from adult and pediatric COVID-19 patients, alongside controls, were analyzed for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, EMMPRIN, TNF-alpha, TIMP-1, TIMP-2, TIMP-3, and TIMP-4. A subset of adult patients received treatment with glucocorticoids, tocilizumab, and convalescent plasma, and MMP levels were compared with those of untreated patients. RESULTS Elevated levels of MMP-1, MMP-7, TIMP-1, and TIMP-2 were observed in adult and pediatric patients. Adult patients displayed higher concentrations of MMP-3, MMP-8, MMP-9, TNF-alpha, and TIMP-4 than children. Post-treatment reduction in MMP-1, MMP-8, MMP-9 levels was observed, with median decreases from 21% to 70%. MMP-3 and MMP-7 remained largely unchanged, and MMP-2 concentrations increased after treatment. Notably, anti-inflammatory treatment correlated with reduced post-treatment MMP levels, suggesting potential therapeutic benefit. CONCLUSIONS Distinctive inflammatory responses in COVID-19 were evident between adults and children. While certain MMPs exhibited post-treatment reduction, the persistence of elevated levels raises concerns about potential long-term consequences, including lung fibrosis. Our findings emphasize the need for personalized treatment strategies and further investigation into the dynamics of MMP regulation in COVID-19.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18years old recruited onto the multicenter EoE CONNECT registrywas performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.